Adipocytes: Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.Adipocytes, White: Fat cells with light coloration and few MITOCHONDRIA. They contain a scant ring of CYTOPLASM surrounding a single large lipid droplet or vacuole.3T3-L1 Cells: A continuous cell line that is a substrain of SWISS 3T3 CELLS developed though clonal isolation. The mouse fibroblast cells undergo an adipose-like conversion as they move to a confluent and contact-inhibited state.Adipose Tissue: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.Lipolysis: The metabolic process of breaking down LIPIDS to release FREE FATTY ACIDS, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the DIGESTIVE TRACT, circulating lipids in the BLOOD, and stored lipids in the ADIPOSE TISSUE or the LIVER. A number of enzymes are involved in such lipid hydrolysis, such as LIPASE and LIPOPROTEIN LIPASE from various tissues.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Glucose Transporter Type 4: A glucose transport protein found in mature MUSCLE CELLS and ADIPOCYTES. It promotes transport of glucose from the BLOOD into target TISSUES. The inactive form of the protein is localized in CYTOPLASMIC VESICLES. In response to INSULIN, it is translocated to the PLASMA MEMBRANE where it facilitates glucose uptake.Adipogenesis: The differentiation of pre-adipocytes into mature ADIPOCYTES.Adipose Tissue, Brown: A thermogenic form of adipose tissue composed of BROWN ADIPOCYTES. It is found in newborns of many species including humans, and in hibernating mammals. Brown fat is richly vascularized, innervated, and densely packed with MITOCHONDRIA which can generate heat directly from the stored lipids.Adipose Tissue, White: Fatty tissue composed of WHITE ADIPOCYTES and generally found directly under the skin (SUBCUTANEOUS FAT) and around the internal organs (ABDOMINAL FAT). It has less vascularization and less coloration than the BROWN FAT. White fat provides heat insulation, mechanical cushion, and source of energy.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Monosaccharide Transport Proteins: A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.PPAR gamma: A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR ALPHA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES. It is a target of THIAZOLIDINEDIONES for control of DIABETES MELLITUS.Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Egg White: The white of an egg, especially a chicken's egg, used in cooking. It contains albumin. (Random House Unabridged Dictionary, 2d ed)Obesity: A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).Leptin: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.Adiponectin: A 30-kDa COMPLEMENT C1Q-related protein, the most abundant gene product secreted by FAT CELLS of the white ADIPOSE TISSUE. Adiponectin modulates several physiological processes, such as metabolism of GLUCOSE and FATTY ACIDS, and immune responses. Decreased plasma adiponectin levels are associated with INSULIN RESISTANCE; TYPE 2 DIABETES MELLITUS; OBESITY; and ATHEROSCLEROSIS.Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Sterol Esterase: An enzyme that catalyzes the hydrolysis of CHOLESTEROL ESTERS and some other sterol esters, to liberate cholesterol plus a fatty acid anion.Receptors, Adrenergic, beta-3: A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The beta-3 adrenergic receptors are the predominant beta-adrenergic receptor type expressed in white and brown ADIPOCYTES and are involved in modulating ENERGY METABOLISM and THERMOGENESIS.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Mice, Obese: Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Insulin Receptor Substrate Proteins: A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.Epididymis: The convoluted cordlike structure attached to the posterior of the TESTIS. Epididymis consists of the head (caput), the body (corpus), and the tail (cauda). A network of ducts leaving the testis joins into a common epididymal tubule proper which provides the transport, storage, and maturation of SPERMATOZOA.3-O-Methylglucose: A non-metabolizable glucose analogue that is not phosphorylated by hexokinase. 3-O-Methylglucose is used as a marker to assess glucose transport by evaluating its uptake within various cells and organ systems. (J Neurochem 1993;60(4):1498-504)European Continental Ancestry Group: Individuals whose ancestral origins are in the continent of Europe.Glucose Transporter Type 1: A ubiquitously expressed glucose transporter that is important for constitutive, basal GLUCOSE transport. It is predominately expressed in ENDOTHELIAL CELLS and ERYTHROCYTES at the BLOOD-BRAIN BARRIER and is responsible for GLUCOSE entry into the BRAIN.Thiazolidinediones: THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).Nerve Fibers, Myelinated: A class of nerve fibers as defined by their structure, specifically the nerve sheath arrangement. The AXONS of the myelinated nerve fibers are completely encased in a MYELIN SHEATH. They are fibers of relatively large and varied diameters. Their NEURAL CONDUCTION rates are faster than those of the unmyelinated nerve fibers (NERVE FIBERS, UNMYELINATED). Myelinated nerve fibers are present in somatic and autonomic nerves.Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Hypoglycemic Agents: Substances which lower blood glucose levels.Subcutaneous Fat: Fatty tissue under the SKIN through out the body.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.MethylglucosidesCarrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Mice, Inbred C57BLFatty Acids: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Adipokines: Polypeptides produced by the ADIPOCYTES. They include LEPTIN; ADIPONECTIN; RESISTIN; and many cytokines of the immune system, such as TUMOR NECROSIS FACTOR-ALPHA; INTERLEUKIN-6; and COMPLEMENT FACTOR D (also known as ADIPSIN). They have potent autocrine, paracrine, and endocrine functions.Phenylisopropyladenosine: N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent.CCAAT-Enhancer-Binding Protein-alpha: A CCAAT-enhancer-binding protein found in LIVER; ADIPOSE TISSUE; INTESTINES; LUNG; ADRENAL GLANDS; PLACENTA; OVARY and peripheral blood mononuclear cells (LEUKOCYTES, MONONUCLEAR). Experiments with knock-out mice have demonstrated that CCAAT-enhancer binding protein-alpha is essential for the functioning and differentiation of HEPATOCYTES and ADIPOCYTES.PhosphoproteinsInsulin Antagonists: Compounds which inhibit or antagonize the biosynthesis or action of insulin.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Lipid Mobilization: LIPOLYSIS of stored LIPIDS in the ADIPOSE TISSUE to release FREE FATTY ACIDS. Mobilization of stored lipids is under the regulation of lipolytic signals (CATECHOLAMINES) or anti-lipolytic signals (INSULIN) via their actions on the hormone-sensitive LIPASE. This concept does not include lipid transport.Thermogenesis: The generation of heat in order to maintain body temperature. The uncoupled oxidation of fatty acids contained within brown adipose tissue and SHIVERING are examples of thermogenesis in MAMMALS.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Cystinyl Aminopeptidase: A zinc-containing sialoglycoprotein that is used to study aminopeptidase activity in the pathogenesis of hypertension. EC 3.4.11.3.Fatty Acid-Binding Proteins: Intracellular proteins that reversibly bind hydrophobic ligands including: saturated and unsaturated FATTY ACIDS; EICOSANOIDS; and RETINOIDS. They are considered a highly conserved and ubiquitously expressed family of proteins that may play a role in the metabolism of LIPIDS.TriglyceridesAdrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Kinetics: The rate dynamics in chemical or physical systems.Adrenergic beta-3 Receptor Agonists: Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.Lipids: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESReverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Resistin: A 12-kDa cysteine-rich polypeptide hormone secreted by FAT CELLS in the ADIPOSE TISSUE. It is the founding member of the resistin-like molecule (RELM) hormone family. Resistin suppresses the ability of INSULIN to stimulate cellular GLUCOSE uptake.African Continental Ancestry Group: Individuals whose ancestral origins are in the continent of Africa.Omentum: A double-layered fold of peritoneum that attaches the STOMACH to other organs in the ABDOMINAL CAVITY.Receptors, Adrenergic, beta: One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cyclic Nucleotide Phosphodiesterases, Type 3: A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. In addition multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing.DioxolesLipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3.Fatty Acids, Nonesterified: FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form.Hormones, Ectopic: Hormones released from neoplasms or from other cells that are not the usual sources of hormones.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.White spot syndrome virus 1: A species of DNA virus, in the genus WHISPOVIRUS, infecting PENAEID SHRIMP.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Fatty Acid Synthases: Enzymes that catalyze the synthesis of FATTY ACIDS from acetyl-CoA and malonyl-CoA derivatives.Rats, Zucker: Two populations of Zucker rats have been cited in research--the "fatty" or obese and the lean. The "fatty" rat (Rattus norvegicus) appeared as a spontaneous mutant. The obese condition appears to be due to a single recessive gene.Glycerolphosphate DehydrogenaseRats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Diet, High-Fat: Consumption of excessive DIETARY FATS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Diffusion Tensor Imaging: The use of diffusion ANISOTROPY data from diffusion magnetic resonance imaging results to construct images based on the direction of the faster diffusing molecules.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Mesenchymal Stromal Cells: Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Intra-Abdominal Fat: Fatty tissue inside the ABDOMINAL CAVITY, including visceral fat and retroperitoneal fat. It is the most metabolically active fat in the body and easily accessible for LIPOLYSIS. Increased visceral fat is associated with metabolic complications of OBESITY.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Epinephrine: The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados.CCAAT-Enhancer-Binding Proteins: A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.Lipogenesis: De novo fat synthesis in the body. This includes the synthetic processes of FATTY ACIDS and subsequent TRIGLYCERIDES in the LIVER and the ADIPOSE TISSUE. Lipogenesis is regulated by numerous factors, including nutritional, hormonal, and genetic elements.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Leukoencephalopathies: Any of various diseases affecting the white matter of the central nervous system.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.ThiazolesSterol Regulatory Element Binding Protein 1: A sterol regulatory element binding protein that regulates expression of GENES involved in FATTY ACIDS metabolism and LIPOGENESIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING.Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)Nicotinamide Phosphoribosyltransferase: An enzyme that catalyzes the formation of nicotinamide mononucleotide (NMN) from nicotinamide and 5-phosphoribosyl-1-pyrophosphate, the rate-limiting step in the biosynthesis of the NAD coenzyme. It is also known as a growth factor for early B-LYMPHOCYTES, or an ADIPOKINE with insulin-mimetic effects (visfatin).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Chromans: Benzopyrans saturated in the 2 and 3 positions.HexosesPalmitic Acid: A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids.3',5'-Cyclic-AMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.Oleic Acid: An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed)Cell Size: The quantity of volume or surface area of CELLS.Azo CompoundsGene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Interleukin-6: A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Complement Factor D: A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.1-Acylglycerol-3-Phosphate O-Acyltransferase: An enzyme that catalyzes the acyl group transfer of ACYL COA to 1-acyl-sn-glycerol 3-phosphate to generate 1,2-diacyl-sn-glycerol 3-phosphate. This enzyme has alpha, beta, gamma, delta and epsilon subunits.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.Diffusion Magnetic Resonance Imaging: A diagnostic technique that incorporates the measurement of molecular diffusion (such as water or metabolites) for tissue assessment by MRI. The degree of molecular movement can be measured by changes of apparent diffusion coefficient (ADC) with time, as reflected by tissue microstructure. Diffusion MRI has been used to study BRAIN ISCHEMIA and tumor response to treatment.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.rab4 GTP-Binding Proteins: A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in recycling of proteins such as cell surface receptors from early endosomes to the cell surface. This enzyme was formerly listed as EC 3.6.1.47.Cold Temperature: An absence of warmth or heat or a temperature notably below an accustomed norm.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Adiposity: The amount of fat or lipid deposit at a site or an organ in the body, an indicator of body fat status.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Deoxy SugarsMitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Receptors, Leptin: Cell surface receptors for obesity factor (LEPTIN), a hormone secreted by the WHITE ADIPOCYTES. Upon leptin-receptor interaction, the signal is mediated through the JAK2/STAT3 pathway to regulate food intake, energy balance and fat storage.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Caveolae: Endocytic/exocytic CELL MEMBRANE STRUCTURES rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in ENDOCYTOSIS (potocytosis), transcytosis, and SIGNAL TRANSDUCTION. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of CAVEOLINS.CCAAT-Enhancer-Binding Protein-beta: A CCAAT-enhancer-binding protein found in LIVER; INTESTINES; LUNG and ADIPOSE TISSUE. It is an important mediator of INTERLEUKIN-6 signaling.Blood Glucose: Glucose in blood.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Subcutaneous Fat, Abdominal: Fatty tissue under the SKIN in the region of the ABDOMEN.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Caveolin 1: A tyrosine phosphoprotein that plays an essential role in CAVEOLAE formation. It binds CHOLESTEROL and is involved in LIPIDS transport, membrane traffic, and SIGNAL TRANSDUCTION.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Acetyl-CoA Carboxylase: A carboxylating enzyme that catalyzes the conversion of ATP, acetyl-CoA, and HCO3- to ADP, orthophosphate, and malonyl-CoA. It is a biotinyl-protein that also catalyzes transcarboxylation. The plant enzyme also carboxylates propanoyl-CoA and butanoyl-CoA (From Enzyme Nomenclature, 1992) EC 6.4.1.2.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.Bucladesine: A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)Complement C3a: The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Anti-Obesity Agents: Agents that increase energy expenditure and weight loss by neural and chemical regulation. Beta-adrenergic agents and serotoninergic drugs have been experimentally used in patients with non-insulin dependent diabetes mellitus (NIDDM) to treat obesity.Palmitates: Salts and esters of the 16-carbon saturated monocarboxylic acid--palmitic acid.Fatty Acid Transport Proteins: A broad category of membrane transport proteins that specifically transport FREE FATTY ACIDS across cellular membranes. They play an important role in LIPID METABOLISM in CELLS that utilize free fatty acids as an energy source.Diabetes Mellitus, Type 2: A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Cell Compartmentation: A partitioning within cells due to the selectively permeable membranes which enclose each of the separate parts, e.g., mitochondria, lysosomes, etc.
Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. (1/132)
Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide (LPS) activates toll-like receptors (TLRs) to cause inflammation. For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-kappaB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold (P<0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-alpha and IL-6 secretion (IL-6, CONTROL: 2.7+/-0.5 vs. LPS: 4.8+/-0.3 ng/ml; P<0.001; TNF-alpha, CONTROL: 1.0+/-0.83 vs. LPS: 32.8+/-6.23 pg/ml; P<0.001). NF-kappaB inhibitor reduced IL-6 in AbdSc adipocytes ( CONTROL: 2.7+/-0.5 vs. NF-kappaB inhibitor: 2.1+/-0.4 ng/ml; P<0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-kappaB was increased in T2DM patients (P<0.05), and TLR-2, TRAF-6, and NF-kappaB were increased in LPS-treated adipocytes (P<0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls (r=0.678, P<0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P=0.0395) and serum LPS (reduced by 35%, P=0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM. (+info)Oncogenic steroid receptor coactivator-3 is a key regulator of the white adipogenic program. (2/132)
The white adipocyte is at the center of dysfunctional regulatory pathways in various pathophysiological processes, including obesity, diabetes, inflammation, and cancer. Here, we show that the oncogenic steroid receptor coactivator-3 (SRC-3) is a critical regulator of white adipocyte development. Indeed, in SRC-3(-/-) mouse embryonic fibroblasts, adipocyte differentiation was severely impaired, and reexpression of SRC-3 was able to restore it. The early stages of adipocyte differentiation are accompanied by an increase in nuclear levels of SRC-3, which accumulates to high levels specifically in the nucleus of differentiated fat cells. Moreover, SRC-3(-/-) animals showed reduced body weight and adipose tissue mass with a significant decrease of the expression of peroxisome proliferator-activated receptor gamma2 (PPARgamma2), a master gene required for adipogenesis. At the molecular level, SRC-3 acts synergistically with the transcription factor CAAT/enhancer-binding protein to control the gene expression of PPARgamma2. Collectively, these data suggest a crucial role for SRC-3 as an integrator of the complex transcriptional network controlling adipogenesis. (+info)Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue. (3/132)
Serum leptin levels are upregulated in proportion to body fat and also increase over the short term in response to meals or insulin. To understand the mechanisms involved, we assessed leptin synthesis and secretion in samples of adipose tissue from subjects with a wide range of BMI. Tissue leptin content and relative rates of leptin biosynthesis, as determined by metabolic labeling, were highly correlated with each other and with BMI and fat cell size. To understand mechanisms regulating leptin synthesis in obesity, we used biosynthetic labeling to directly assess the effects of insulin and glucocorticoids (dexamethasone) on leptin synthesis and secretion in human adipose tissue. Chronic treatment (1-2 days in organ culture) with insulin increased relative rates of leptin biosynthesis without affecting leptin mRNA levels. In contrast, dexamethasone increased leptin mRNA and biosynthesis in parallel. Acute treatment with insulin or dexamethasone (added during 1-h preincubation and 45-min pulse labeling) did not affect relative rates of leptin biosynthesis, but pulse-chase studies showed that addition of insulin nearly doubled the release of [35S]leptin after a 1-h chase. We conclude that the higher leptin stores in adipose tissue of obese humans are maintained by chronic effects of insulin and glucocorticoids acting at pre- and posttranslational levels and that the ability of insulin to increase the release of preformed leptin may contribute to short-term variations in circulating leptin levels. (+info)Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro. (4/132)
Obesity, a risk factor for colon cancer, is associated with elevated serum levels of leptin, a protein produced by adipocytes. The aim of the present study was to clarify the effects of adipose tissue on colon cancer proliferation by using cultured cell lines. To achieve this, colon cancer cells (CACO-2, T84, and HT29) were cocultured with adipose tissue, isolated mature adipocytes, and isolated preadipocytes in a three-dimensional collagen gel culture system. The adipocytes and preadipocytes used were isolated from C57BL/6J and leptin-deficient ob/ob mice. Proliferation of the cancer cells was evaluated by nuclear bromodeoxyuridine uptake. The adipose tissue, mature adipocytes, and preadipocytes isolated from C57BL/6J mice significantly increased the proliferation of the colon cancer cells. This trophic effect of mature adipocytes on the cancer cell lines was observed only for cells from lean littermates and not for those from ob/ob mice. In contrast, the trophic effect of preadipocytes was not abolished in ob/ob mice, and this finding was supported by the result that leptin had a trophic effect on cancer cells. In conclusion, adipocytes were able to enhance the proliferation of colon cancer cells in vitro, partly via leptin, suggesting that adipose tissues, including mature adipocytes and preadipocytes, may promote the growth of colorectal cancer. (+info)Effects of forced uncoupling protein 1 expression in 3T3-L1 cells on mitochondrial function and lipid metabolism. (5/132)
Obesity-related increase in body fat mass is a risk factor for many diseases, including type 2 diabetes. Controlling adiposity by targeted modulation of adipocyte enzymes could offer an attractive alternative to current dietary approaches. Brown adipose tissue, which is present in rodents but not in adult humans, expresses the mitochondrial uncoupling protein 1 (UCP1) that promotes cellular energy dissipation as heat. Here, we report on the direct metabolic effects of forced UCP1 expression in white adipocytes derived from a murine (3T3-L1) preadipocyte cell line. After stable integration, the ucp1 gene product was continuously expressed during differentiation and reduced the total lipid accumulation by approximately 30% without affecting other adipocyte markers, such as cytosolic glycerol-3-phosphate dehydrogenase activity and leptin production. The expression of UCP1 also decreased glycerol output and increased glucose uptake, lactate output, and the sensitivity of cellular ATP content to nutrient removal. However, oxygen consumption and beta-oxidation were minimally affected. Together, our results suggest that the reduction in intracellular lipid by constitutive expression of UCP1 reflects a downregulation of fat synthesis rather than an upregulation of fatty acid oxidation. (+info)Suppression by licorice flavonoids of abdominal fat accumulation and body weight gain in high-fat diet-induced obese C57BL/6J mice. (6/132)
We applied licorice flavonoid oil (LFO) to high-fat diet-induced obese C57BL/6J mice and investigated its effect. LFO contains hydrophobic flavonoids obtained from licorice by extraction with ethanol. The oil is a mixture of medium-chain triglycerides, having glabridin, a major flavonoid of licorice, concentrated to 1.2% (w/w). Obese mice were fed on a high-fat diet containing LFO at 0 (control), 0.5%, 1.0%, or 2.0% for 8 weeks. Compared with mice in the control group, those in the 1% and 2% LFO groups efficiently reduced the weight of abdominal white adipose tissues and body weight gain. A histological examination revealed that the adipocytes became smaller and the fatty degenerative state of the hepatocytes was improved in the 2% LFO group. A DNA microarray analysis of the liver showed up-regulation of those genes for beta-oxidation and down-regulation of those for fatty acid synthesis in the 2% LFO group. These findings suggest that LFO prevented and ameliorated diet-induced obesity via the regulation of lipid metabolism-related gene expression in the liver. (+info)Impaired adipogenesis caused by a mutated thyroid hormone alpha1 receptor. (7/132)
Thyroid hormone (T3) is critical for growth, differentiation, and maintenance of metabolic homeostasis. Mice with a knock-in mutation in the thyroid hormone receptor alpha gene (TRalpha1PV) were created previously to explore the roles of mutated TRalpha1 in vivo. TRalpha1PV is a dominant negative mutant with a frameshift mutation in the carboxyl-terminal 14 amino acids that results in the loss of T3 binding and transcription capacity. Homozygous knock-in TRalpha1(PV/PV) mice are embryonic lethal, and heterozygous TRalpha1(PV/+) mice display the striking phenotype of dwarfism. These mutant mice provide a valuable tool for identifying the defects that contribute to dwarfism. Here we show that white adipose tissue (WAT) mass was markedly reduced in TRalpha1(PV/+) mice. The expression of peroxisome proliferator-activated receptor gamma (PPARgamma), the key regulator of adipogenesis, was repressed at both mRNA and protein levels in WAT of TRalpha1(PV/+) mice. Moreover, TRalpha1PV acted to inhibit the transcription activity of PPARgamma by competition with PPARgamma for binding to PPARgamma response elements and for heterodimerization with the retinoid X receptors. The expression of TRalpha1PV blocked the T3-dependent adipogenesis of 3T3-L1 cells and repressed the expression of PPARgamma. Thus, mutations of TRalpha1 severely affect adipogenesis via cross talk with PPARgamma signaling. The present study suggests that defects in adipogenesis could contribute to the phenotypic manifestation of reduced body weight in TRalpha1(PV/+) mice. (+info)Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation. (8/132)
White adipose tissue (WAT) mass is the main determinant of obesity and associated health risks. WAT expansion results from increases in white adipocyte cell number and size, which in turn reflect a series of shifts in the cellular metabolic state. To quantitatively profile the metabolic alterations occurring during de novo adipocyte formation, metabolic flux analysis (MFA) was used in conjunction with a novel modularity analysis algorithm on differentiating 3T3-L1 preadipocytes. Use of a type I collagen gel as an effective long-term culture substrate was also assessed. The calculated flux distributions predicted the sequential activation of several intracellular cross-compartmental pathways, including lipogenesis, the pentose phosphate pathway, and the malate cycle, in good agreement with earlier isotopic tracer experiments and gene profiling studies. Partition of the adipocyte metabolic network into highly interacting reaction subgroups suggested a functional reorganization of the major pathways consistent with the lipid-loading phenotype of the adipocyte. Flux and modularity analysis results together point to the flux distribution around pyruvate as a key indicator of adipocyte lipid accumulation. (+info)
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Brown adipose tissueIn contrast to white adipocytes, which contain a single lipid droplet, brown adipocytes contain numerous smaller droplets and a ... The second develops from white adipocytes that are stimulated by the sympathetic nervous system. These adipocytes are found ... Both adipocytes and brown adipocyte may be derived from pericytes, the cells which surround the blood vessels that run through ... Brown adipose tissue (BAT) or brown fat makes up the adipose organ together with white adipose tissue (or white fat). Brown ...
Lo, KA; Sun, L (2013). "Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes". Bioscience ... Rosenwald, M; Perdikari, A; Rülicke, T; Wolfrum, C (2013). "Bi-directional interconversion of brite and white adipocytes". ... Pre-adipocytes are undifferentiated fibroblasts that can be stimulated to form adipocytes. Recent studies shed light into ... a phenotype distinguishing brown adipocytes from interscapular brown adipose tissue and white adipose tissue". The Journal of ...
The activity of PRDM16 in white adipose tissue leads to the production of brown fat-like adipocytes within white adipose tissue ... Brown adipocytes consist of densely packed mitochondria that contain uncoupling protein 1 (UCP-1). UCP-1 plays a key role in ... White adipose tissue (WAT) primarily stores excess energy in the form of triglycerides. Recent research has shown that PRDM16 ... PRDM16 is highly enriched in brown adipose cells as compared to white adipose cells, and plays a role in these thermogenic ...
Rosenwald M, Perdikari A, Rülicke T, Wolfrum C (June 2013). "Bi-directional interconversion of brite and white adipocytes". ... Pre-adipocytes are undifferentiated fibroblasts that can be stimulated to form adipocytes. Recent studies shed light into ... "EBF2 promotes the recruitment of beige adipocytes in white adipose tissue". Molecular Metabolism. 5 (1): 57-65. doi:10.1016/j. ... a review on regulators controlling the browning of white adipocytes". Bioscience Reports. 33 (5): 711-19. doi:10.1042/ ...
PLIN4 is a member of the perilipin family, a group of proteins that coat lipid droplets in adipocytes, the adipose tissue cells ... It is highly expressed in white adipose tissue, with lower expression in heart, skeletal muscle, and brown adipose tissue. ... PLIN4 coats lipid droplets in adipocytes to protect them from lipases. The PLIN4 gene may be associated with insulin resistance ... Wolins NE, Skinner JR, Schoenfish MJ, Tzekov A, Bensch KG, Bickel PE (September 2003). "Adipocyte protein S3-12 coats nascent ...
... is produced primarily in the adipocytes of white adipose tissue. It also is produced by brown adipose tissue, placenta ( ... Adipocytes interact with other cells through producing and secreting a variety of signalling molecules, including the cell ... Conde J, Scotece M, Gómez R, López V, Gómez-Reino JJ, Lago F, Gualillo O (2011). "Adipokines: biofactors from white adipose ... Hui W, Litherland GJ, Elias MS, Kitson GI, Cawston TE, Rowan AD, Young DA (2012). "Leptin produced by joint white adipose ...
"Pluripotent Stem Cells Derived from Mouse and Human White Mature Adipocytes". Stem Cells Translational Medicine. 3 (2): 161-71 ... Ghaedi, M.; Calle, E. A.; Mendez, J. J.; Gard, A. L.; Balestrini, J.; Booth, A.; Bove, P. F.; Gui, L.; White, E. S.; Niklason, ... See also overview A specialised type of white blood cell, known as cytotoxic T lymphocytes (CTLs), are produced by the immune ... That distinguishes them from most nonpluripotent cells, although not white blood cells. The glycans on the stem cell surface ...
"Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ". Nature. 429 (6993): 771-6. Bibcode:2004Natur.429.. ...
White-to-brown metabolic conversion of human adipocytes by JAK inhibition. Nature Cell Biology, 8 December 2014. doi:10.1038/ ... A 2014 study showed that tofacitinib treatment was able to convert white fat tissues into more metabolically active brown fat, ...
"Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma". Nature. 429 (6993): 771-76. Bibcode:2004Natur. ...
"Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase ... "Irisin exerts dual effects on browning and adipogenesis of human white adipocytes". American Journal of Physiology. ... Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin JD, Greenberg ME, Spiegelman BM (November 2013). " ... A 2016 in vitro study of white and brown fat cell tissue found dose-related upregulation of a protein called UCP1 that ...
"Stress-induced alteration in the lipolytic response to β-adrenoceptor agonists in rat white adipocytes". JLR.org. Retrieved ...
"Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages". ... However, its expression is limited to brown and not white adipose precursors, providing part of the developmental separation ...
Argetsinger LS, Norstedt G, Billestrup N, White MF, Carter-Su C (1996). "Growth hormone, interferon-gamma, and leukemia ... "Hyperosmotic stress inhibits insulin receptor substrate-1 function by distinct mechanisms in 3T3-L1 adipocytes". J. Biol. Chem ...
... of erythrocytes and white adipocytes by the accumulation of triphenylmethylphosphonium cation". J. Membr. Biol. 56 (3): 191-201 ...
White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J ... is required for adipocyte differentiation". The Journal of Biological Chemistry. 275 (22): 16845-50. doi:10.1074/jbc.275.22. ... Kim TA, Ota S, Jiang S, Pasztor LM, White RA, Avraham S (Sep 2000). "Genomic organization, chromosomal localization and ...
The skin color of people with light skin is determined mainly by the bluish-white connective tissue under the dermis and by the ... The main cell types are fibroblasts, macrophages and adipocytes (subcutaneous tissue contains 50% of body fat). Fat serves as ... Human skin shows high skin color variety from the darkest brown to the lightest pinkish-white hues. Human skin shows higher ...
... white, unlabelled) adipocytes in vivo. Products of endocrine system such as insulin, IGF-1, cAMP, glucocorticoid,and ... Adipogenesis is the process of cell differentiation by which pre-adipocytes become adipocytes. Adipogenesis has been one of the ... Adipocytes play a vital role in energy homeostasis and process the largest energy reserve as triglycerol in the body of animals ... Adipocytes stay in a dynamic state, they start expanding when the energy intake is higher than the expenditure and undergo ...
... stavudine and zidovudine involves multiple cellular targets in white and brown adipocytes". Antivir. Ther. (Lond.). 12 (6): 919 ... in white fat cells but not brown fat cells. Since stavudine and zidovudine are OAT1 substrates, they may have similar effects ...
"Secretion of fatty acid binding protein aP2 from adipocytes through a nonclassical pathway in response to adipocyte lipase ... Burak, M. Furkan; Inouye, Karen E.; White, Ariel; Lee, Alexandra; Tuncman, Gurol; Calay, Ediz S.; Sekiya, Motohiro; Tirosh, ...
Grounds, MD; White, JD; Rosenthal, N; Bogoyevitch, MA (May 2002). "The role of stem cells in skeletal and cardiac muscle repair ... Angptl2 is an adipocyte-derived inflammatory mediator linking obesity to systemic insulin resistance. It is possible that, as ... Trappe, TA; White, F; Lambert, CP; Cesar, D; Hellerstein, M; Evans, WJ (March 2002). "Effect of ibuprofen and acetaminophen on ... White blood cells then assist by releasing more cytokines. This link between adiposity and inflammation has been shown to ...
... suggesting chemerin plays a role in metabolic function of mature adipocytes. Studies using mature human adipocytes, 3T3-L1 ... In humans, chemerin mRNA is highly expressed in white adipose tissue, liver and lung while its receptor, CMKLR1 is ... Because of its role in adipocyte differentiation and glucose uptake, chemerin is classified as an adipokine. Chemerin has been ... Studies with 3T3-L1 cells have shown chemerin expression is low in pre-differentiated adipocytes but its expression and ...
Brown NF, Hill JK, Esser V, Kirkland JL, Corkey BE, Foster DW, McGarry JD (Oct 1997). "Mouse white adipocytes and 3T3-L1 cells ...
... treatment of adipocytes is associated with phosphorylation of FRS2, a protein linking FGF receptors to the Ras/MAP kinase ... FGF21 expression is also induced in white adipose tissue by PPAR-gamma, which may indicate it also regulates metabolism in the ... FGF21 stimulates glucose uptake in adipocytes but not in other cell types. This effect is additive to the activity of insulin. ... Activation of AMPK and SIRT1 by FGF21 in adipocytes enhanced mitochondrial oxidative capacity as demonstrated by increases in ...
The hormone leptin is primarily manufactured in the adipocytes of white adipose tissue, which also produces another hormone, ... White adipose tissue (WAT) or white fat is one of the two types of adipose tissue found in mammals. The other kind of adipose ... White adipose tissue is used as a store of energy. Upon release of insulin from the pancreas, white adipose cells' insulin ... In healthy, non-overweight humans, white adipose tissue composes as much as 20% of the body weight in men and 25% of the body ...
The cells of connective tissue include fibroblasts, adipocytes, macrophages, mast cells and leucocytes. ... and are as diverse as brown and white adipose tissue, blood, cartilage and bone.[15]:158 Cells of the immune system, such as ...
Association between asthma and serum adiponectin concentration in women | ThoraxAdipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005;46: ... During 1985 and 1986 CARDIA recruited 5115 black and white men and women aged 18-30 years from four clinical centres in ... Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease. J Surg Res 2005;126:121-9. ... Although central (visceral) adipocytes are the most important source of adiponectin,11 the serum adiponectin concentration does ...
Thus, Tbx15 differentially regulates metabolism in white adipocytes and leads to a functional heterogeneity in white fat cells ... Tbx15 Defines a Glycolytic Subpopulation and White Adipocyte Heterogeneity. Kevin Y. Lee, Rita Sharma, Grant Gase, Siegfried ... Tbx15 Defines a Glycolytic Subpopulation and White Adipocyte Heterogeneity. Kevin Y. Lee, Rita Sharma, Grant Gase, Siegfried ... Intrinsic differences in adipocyte precursor cells from different white fat depots. Diabetes 2012;61:1691-1699pmid:22596050. ...
Comparative Secretome Analyses of Primary Murine White and Brown Adipocytes Reveal Novel Adipokines | Molecular & Cellular...Comparative Secretome Analyses of Primary Murine White and Brown Adipocytes Reveal Novel Adipokines. Asrar Ali Khan, Jenny ... Comparative Secretome Analyses of Primary Murine White and Brown Adipocytes Reveal Novel Adipokines ... Comparative Secretome Analyses of Primary Murine White and Brown Adipocytes Reveal Novel Adipokines ... Comparative Secretome Analyses of Primary Murine White and Brown Adipocytes Reveal Novel Adipokines ...
... ... Differentiated HIB1B brown adipocytes treated with serotonin had reduced levels of the thermogenic markers uncoupling protein 1 ... It has recently been shown that serotonin leads to fat accumulation in white adipose tissue (WAT). However, the direct effect ... In parallel, serotonin led to 3-6-fold reduction in the gene expression of brown adipocyte differentiation markers, that is, ...
Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy. - PubMed - NCBID) Markers of brown and white adipocytes were assessed in the interscapular BAT by qPCR. (E and F) Five-month-old mice were ... Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy.. Mori MA, Thomou T, ... Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte-like phenotype and reduced expression of ... Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy ...
Frontiers | TGF-β/Smad3 Signaling Regulates Brown Adipocyte Induction in White Adipose Tissue | EndocrinologyHere we review the data supporting this phenomenon and put into perspective the promise of conversion of white fat to a brown ... Here we review the data supporting this phenomenon and put into perspective the promise of conversion of white fat to a brown ... role played by the TGF-beta/Smad3 signaling pathway in modulating the appearance of brown adipocytes in traditional white fat, ... role played by the TGF-beta/Smad3 signaling pathway in modulating the appearance of brown adipocytes in traditional white fat, ...
... induced emergence of brown-like adipocytes in white adipose tissue (WAT) of the spontaneously hypertensive rat (SHR). We ... In this study, we present evidence for high-fat diet (HFD)-induced emergence of brown-like adipocytes in white adipose tissue ( ... indicating the emergence of brown-like adipocytes in WAT. Our results suggest that SHR may have the capacity to increase energy ... expenditure in response to a chronic HFD that may be linked to the emergence of brown-like adipocytes in WAT. Thus, the SHR may ...
We suggest that obesity-linked hypoxia may lead to similar alterations in brown adipocytes as in white fat cells - particularly ... We suggest that obesity-linked hypoxia may lead to similar alterations in brown adipocytes as in white fat cells - particularly ... and this leads to substantial changes in white adipocyte function. These changes include increased production of inflammation- ... and this leads to substantial changes in white adipocyte function. These changes include increased production of inflammation- ...
White adipocytes store energy (e.g., triglycerides), whereas brown adipocytes consume energy (5,6). Many studies have shown ... A: Expression of brown/beige adipocyte marker, betatrophin, and white adipocyte marker (aP2 and adipoq) genes were measured by ... Irisin stimulates adipocyte browning via p38/ERK pathways. Primary rat adipocytes and 3T3-L1-derived adipocytes were treated ... To investigate the browning effect of r-irisin on adipocytes, we used both 3T3-L1-derived adipocytes and primary rat adipocytes ...
White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axisIn white fat, enrichment induced the upregulation of the brown fat cell fate determining gene Prdm16, brown fat-specific ... White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis Cell ... In white fat, enrichment induced the upregulation of the brown fat cell fate determining gene Prdm16, brown fat-specific ... Moreover, pockets of cells with prototypical brown fat morphology and high UCP1 levels were observed in the white fat of ...
FTIR imaging of structural changes in visceral and subcutaneous adiposity and brown to white adipocyte transdifferentiation -...... visceral and subcutaneous adipose tissues in terms of macromolecular content and investigate transdifferentiation between white ... FTIR imaging of structural changes in visceral and subcutaneous adiposity and brown to white adipocyte transdifferentiation ... FTIR imaging of structural changes in visceral and subcutaneous adiposity and brown to white adipocyte transdifferentiation F. ... with a decrease of UCP1 protein content which might be due to the transdifferentiation of brown adipocytes to white adipocytes ...
Capsaicin Activates the Trpv1-camkii-ampk-sirt-1-dependent Mechanism to Trigger Brown Remodeling of White Adipocytes to ... Capsaicin Activates the Trpv1-camkii-ampk-sirt-1-dependent Mechanism to Trigger Brown Remodeling of White Adipocytes to ... Capsaicin Activates the Trpv1-camkii-ampk-sirt-1-dependent Mechanism to Trigger Brown Remodeling of White Adipocytes to ... Capsaicin Activates the Trpv1-camkii-ampk-sirt-1-dependent Mechanism to Trigger Brown Remodeling of White Adipocytes to ...
white adipocyte. Introduction. White adipose tissue (WAT) is an organ distributed at several locations in the body and with an ... The white adipocyte is now known to be an endocrine cell [1] and adipocyte secretory hormone-containing vesicles can be ... including white adipocytes [15,16,41]. The ATP-induced elevation of adipocyte [Ca2+]i has been shown to involve activation of ... 2014) Etiology of the membrane potential of rat white fat adipocytes. Am. J. Physiol. Endocrinol. Metab. 307, E161-E175 doi: ...
Effects of selected bioactive food compounds on human white adipocyte function | Nutrition & Metabolism | Full TextCell cultures of primary human adipocytes. Primary human pre-adipocytes for in vitro differentiation from 22 female subjects ... No effects of bioactives on adipocyte differentiation. To measure possible effect of bioactives on adipocyte differentiation ... Adipocyte. 2014;4:1-8.Google Scholar. *. Hong YH, Nishimura Y, Hishikawa D, Tsuzuki H, Miyahara H, Gotoh C, et al. Acetate and ... we investigated their role on human white adipocyte function. ... Role of the adipocyte, free fatty acids, and ectopic fat in ...
Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white...In the absence of β3-adrenergic stimulation, differentiation of adipocyte progenitors into white adipocytes in the WAT was ... Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white ... Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white ... Oleoylethanolamide enhances β-adrenergic-mediated thermogenesis and white-to-brown adipocyte phenotype in epididymal white ...
Inhibitory Effects of Toll-Like Receptor 4, NLRP3 Inflammasome, and Interleukin-1β on White Adipocyte Browning | Springer for...... on white adipocyte browning. We report that TLR4 activation by lipopolysaccharide repressed white adipocyte browning in ... Mitochondria in white, brown, and beige adipocytes. Stem cells International 2016: 6067349.CrossRefPubMedCentralPubMedGoogle ... Intrinsic properties of brown and white adipocytes have differential effects on macrophage inflammatory responses. Mediators of ... Inhibitory Effects of Toll-Like Receptor 4, NLRP3 Inflammasome, and Interleukin-1β on White Adipocyte Browning. ...
Adrenoceptors in white, brown, and brite adipocytesIn this review, we have highlighted the role of adrenoceptor subtypes in white, brown, and brite adipocytes in both rodents and ... We discuss important considerations when investigating adrenoceptor function in adipose tissue or adipocytes. ... and the secretion of adipocyte-derived hormones that can control whole-body energy homeostasis. These processes are regulated ... humans and have included detailed analysis of adrenoceptor expression in human adipose tissue and clonally derived adipocytes. ...
Etiology of the membrane potential of rat white fat adipocytes - Nottingham ePrintsReduction of extracellular Cl- elevated the intracellular Ca2+ of adipocytes.. In conclusion, the Vm of white fat adipocyte is ... The plasma membrane potential (Vm) is key to many physiological processes, however its ionic aetiology in white fat adipocytes ... Etiology of the membrane potential of rat white fat adipocytes. AJP: Endocrinology and Metabolism, 307 (2). E161-E175. ISSN ... The resting Vm of primary and 3T3-L1 adipocytes were -32.1±1.2mV (n=95) and -28.8±1.2mV (n=87), respectively. Vm was ...
Brown adipocytes appeared more affected than white adipocytes (lower respiration rate and decreased ATP production). The ... With all the treatments, white adipocytes showed a decrease in the expression of mitochondrial and nuclear-DNA-encoded ... Adipocyte fat content was measured with Oil Red 0 staining. Quantification of mRNA levels and of mitochondrial DNA content used ... gamma2 and aP2 but also uncoupling protein 1 in brown adipocytes) as well as altered mitochondrial function (decreased ...
Adipocytes, White - Semantic ScholarAdipocytes, White. Known as: White Fat Cell, White adipose cell, Adipocyte, White (More). ... Attainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy… ( ... Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ. *Frédéric Picard, Martin V. Kurtev, +6 authors ... Acquirement of brown fat cell features by human white adipocytes.. *Claire Tiraby, Geneviève Tavernier, +4 authors Dominique ...
Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes...White M F, *Spiegelman B M. (1996) Science 271:665-668, pmid:8571133. ... Adipocyte complement-related protein (30 kDa) (Acrp30) is a secreted protein expressed exclusively in differentiated adipocytes ... 30-kDa adipocyte complement-related protein;. gAcrp30,. globular head domain of Acrp30;. TNFα,. tumor necrosis factor-α;. FFA, ... Adipocyte complement-related protein (30 kDa) (Acrp30), a secreted protein of unknown function, is exclusively expressed in ...
Rosenwald M, Wolfrum C (2014) The origin and definition of brite versus white and classical brown adipocytes. Adipocyte 3:4-9 ... However, controversy still surrounds the cellular identity in BMP7-mediated transition of white to brown adipocytes. The aim of ... Rosenwald M, Perdikari A, Rulicke T, Wolfrum C (2013) Bi-directional interconversion of brite and white adipocytes. Nat Cell ... Programming human pluripotent stem cells into white and brown adipocytes. Nat Cell Biol 14:209-219PubMedCentralPubMedCrossRef ...
A: glucose uptake in isolated white adipocytes. Epididymal adipocytes were isolated from 6- to 7-wk-old male AS160−/− (filled ... Parametrial adipocytes (isolated adipocytes), soleus, and EDL were obtained from 10- to 12-wk-old female AS160−/− and AS160+/+ ... GLUT1 expression in isolated adipocytes. Adipocytes were isolated from epididymal and parametrial adipose tissue of 14-wk-old ... Adipocytes were isolated from parametrial fat depots of 8- to 11-wk-old female AS160+/+ (open bars) and AS160−/− mice (filled ...
Biology | Free Full-Text | Groundsel Bush (Baccharis halimifolia) Extract Promotes Adipocyte Differentiation In Vitro and...GB produces metabolically favorable changes in differentiating adipocytes, mature adipocytes, and macrophages in vitro, ... In mature adipocytes, GB reduced the gene expression of resistin, a pro-inflammatory endocrine factor, increased the ... Here, we examine the effects of GB on adipocyte development and function, as these processes are attractive targets for ... In differentiating 3T3-L1 adipocytes, GB enhanced lipid accumulation and increased expression of several adipogenic genes ( ...
ac, white adipocyte. Scale bars: 80 μm. (G) BeAT content of the iAT at P34. (H) CIM showing relative UCP1 level in iAT on P10 ... E) Relative NADH-DH activity of adipocytes. (F) Ucp1 transcription in adipocytes. (G) Oxygen consumption of adipocytes treated ... García-Alonso V, Clària J. Prostaglandin E2 signals white-to-brown adipogenic differentiation. Adipocyte. 2014;3(4):290-296. ... Furthermore, iAT mass and adipocyte size were reduced (Supplemental Figure 14, B and C) and UCP1+ adipocytes were abundant ...
LeptinUCP1PrecursorsClassical brown adipocytesPhenotypeThermogenicBrowningAdipose TissuesVivoMesenchymal stemGene expression in adipocytesMicePrimary adipocytesBeige and brown adipocytesAccumulationMacrophagesConnective tissuePrdm16Quantified in brown adipocytesMitochondrialInducesInductionMRNASecretionActive brown adipocytesTissueMechanismsMature white adipocytesGenesTypes of adiposeHomeostasisRole in adipocyteFunction of adipocytesDropletsDifferentiateVisceralMolecularMETHODS
- One promising approach involves leptin, an adipocyte-derived protein hormone that sends signals that inform the central nervous system on the status of the peripheral energy stores, controlling overall metabolism and food uptake [ 2 , 3 ]. (biomedcentral.com)
- Differentiated HIB1B brown adipocytes treated with serotonin had reduced levels of the thermogenic markers uncoupling protein 1 (UCP1) and fibroblast growth factor 21 (FGF21) and increased levels of UCP2. (ovid.com)
- Brown adipocytes are uniquely characterized by the expression of uncoupling protein-1 (UCP1). (frontiersin.org)
- The results indicated a remarkable increase in the lipid/protein ratio, accompanied with a decrease of UCP1 protein content which might be due to the transdifferentiation of brown adipocytes to white adipocytes in obese groups. (rsc.org)
- Regarding eWAT, CL316243 and OEA treatment elevated levels of the thermogenic factors PPARα and UCP1, reduced p38-MAPK phosphorylation, and promoted brown-like features in the white adipocytes: the mitochondrial ( Cox4i1 , Cox4i2 ) and BAT ( Fgf21 , Prdm16 ) genes were overexpressed in eWAT. (biologists.org)
- In addition, activation of NLRP3 inflammasome in macrophages attenuated UCP1 induction and mitochondrial respiration in cultures of primary adipocytes, while the absence of NLRP3 protected UCP1 in adipocytes. (springer.com)
- Here we show by analysis of Ucp1, a gene which is typically expressed in brown but not white adipocytes, that RIP140 is essential for both DNA and histone methylation to maintain gene repression. (mdx.ac.uk)
- Our results showed that exposure of h ASC to human BMP7 was associated with significant escalation of (1) UCP1 gene expression, a signature gene of brown adipocytes, (2) beige specific marker gene expression (i.e. (springer.com)
- In addition, AT2R-induced browning effect is also observed in human white adipocytes, as evidenced by the increased UCP1 expression and oxygen consumption. (nature.com)
- 1 , 2 In contrast to the notorious WAT that stores energy as lipids, brown adipose tissue (BAT) dissipates energy directly as heat by uncoupling oxidative phosphorylation from adenosine triphosphate (ATP) production through the action of brown adipocyte-specific uncoupling protein 1 (UCP1). (nature.com)
- For examples, TNFα suppresses UCP1 expression in white adipocytes via extracellular signal-related kinase (ERK) activation 11 whereas both apelin and adiponectin enhance WAT browning. (nature.com)
- A screening platform for adipocyte browning was set to identify the induction of UCP1 activation, using a human pluripotent stem cell (PSC)-derived adipocyte model. (gatech.edu)
- As a browning index, UCP1 expression was monitored by UCP1 mRNA capture plates followed by branched DNA ( bDNA ) amplification, and expression of fatty acid binding protein 4 ( FABP4 ), an adipocyte-specific gene served as an internal control to eliminate anti- and pro-adipogenic compounds not specific to UCP1 . (gatech.edu)
- x axis: UCP1 mRNA level as an indicator of adipocyte browning, y axis: FABP4 mRNA as an indicator of general adipogenesis. (gatech.edu)
- and R406 increase UCP1 expression in human primary adipocytes. (gatech.edu)
- ERRγ enhances UCP1 expression and fatty acid oxidation in brown adipocytes. (qxmd.com)
- Gene and protein expression of uncoupling protein 1 (UCP1), a thermogenic protein, was up-regulated in Prip -KO brown adipocytes in thermoneutral or cold environments. (pubmedcentralcanada.ca)
- Moreover, CD1377 knock-out mice showed elevated levels of thermogenic markers, including UCP1, increased numbers of beige adipocyte precursors, and expanded UCP1-expressing cell clusters in inguinal WAT after chronic cold exposure. (carlosibanezlab.se)
- Ectopic expression of TAF7L in myoblasts reprograms these muscle precursors into adipocytes upon induction. (elifesciences.org)
- Beige adipocytes can be induced from white adipocytes and precursors upon stimulation by cold temperatures and act like brown adipocytes to increase energy expenditure. (sciencemag.org)
- Primary mouse brown adipocyte precursors were infected with adenovirus expressing a shRNA directed against PRDM16 to knock-down its expression. (upenn.edu)
- While the cold effect in part may be mediated by IL-4 and its receptor IL-4Ra in the adipocyte precursors, in mature adipose cells a reduction in the IL4Ra is observed and probably this effect may include diverse mediators, including IL-33 and Met-enkephalin [47, (thefreedictionary.com)
- To perform thermogenic function, beige adipocytes, like classical brown adipocytes, take up substantial amounts of glucose and free fatty acids and convert these molecules into heat rather than ATP. (elifesciences.org)
- RNA sequencing followed by whole genome-wide expression analysis shows that beige adipocytes induced from bat aWAT, rather than sWAT, have molecular signatures resembling those of mouse sWAT-induced beige adipocytes and exhibit dynamic profiles similar to those of classical brown adipocytes. (sciencemag.org)
- Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte-like phenotype and reduced expression of several miRNAs. (nih.gov)
- We previously reported that Prip knock-out (KO) mice exhibit a lean phenotype with a small amount of white adipose tissue. (pubmedcentralcanada.ca)
- In the resting phase, they resemble white adipocytes, but upon cold stimulation, they acquire a phenotype similar to that of brown adipocytes along with the thermogenic capacities of such cells ( Sidossis and Kajimura, 2015 ). (promocell.com)
- Furthermore, FGF9 treatment inhibited thermogenic genes in the process of beige adipocytes differentiation from stromal vascular fraction (SVF) in a dose-dependent manner. (bioscientifica.com)
- Consistently, knockdown of FGF9 in SVF cells by using lentiviral shRNA increased thermogenic genes in differentiated beige adipocytes. (bioscientifica.com)
- Over time, beige adipocytes gain a white adipocyte morphology and lose their thermogenic activity. (pnas.org)
- In particular, with time, thermogenic-competent beige adipocytes progressively gain a white adipocyte morphology. (pnas.org)
- (sciencemag.org)
- Our genetic and pharmacologic data suggest a mechanism whereby induction of hypothalamic BDNF expression in response to environmental stimuli leads to selective sympathoneural modulation of white fat to induce "browning" and increased energy dissipation. (nih.gov)
- Here, we investigated the effect of pattern recognition receptors (PRR) activation in macrophages, especially the toll-like receptor 4 (TLR4) and Nod-like receptor 3 (NLRP3), on white adipocyte browning. (springer.com)
- This study shows that adipose-derived FGF9 play as an inhibitory role in the browning of white adipocytes. (bioscientifica.com)
- In Aim 3, we will determine the effect of MRTF-A deficiency on browning of white adipose tissue and energy balance in mice. (grantome.com)
- Finally, we provide evidence that AT2R plays important roles in hormone T3-induced white adipose browning. (nature.com)
- on browning of white adipose tissue and energy expenditure in mice. (grantome.com)
- These results indicate that CD137 functions as a negative regulator of "browning" in white adipose tissue, and call into question the use of this protein as a functional marker for beige adipocytes. (carlosibanezlab.se)
- In a recent animal study, using intravenous injection, the nanoparticles showed significant browning of white fat. (thenextweb.com)
- The current study aims to characterize and compare visceral and subcutaneous adipose tissues in terms of macromolecular content and investigate transdifferentiation between white and brown adipocytes. (rsc.org)
- Vice versa, using GFP reporter mice, we traced the fate of beige adipocytes and showed that adipocyte-specific loss of Lsd1 results in a premature beige-to-white adipocyte transition in vivo. (pnas.org)
- Accordingly, adipocyte-specific increase of Lsd1 expression is sufficient to rescue the age-related transition of beige adipocytes to white adipocytes in vivo, whereas loss of Lsd1 precipitates it. (pnas.org)
- Highly selective in vivo labeling of subcutaneous white adipocyte prec" by Joan Sanchez-Gurmaches, Wen-Yu Hsiao et al. (umassmed.edu)
- The altered ex vivo secretion in adipocytes isolated from Cav1 null mice is accompanied by lowered serum levels of the high-molecular weight (HMW) form of adiponectin, whereas the total concentration of adiponectin is unaltered. (bioscientifica.com)
- Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes, osteoblasts, myocytes and other cell types through adipogenesis. (wikipedia.org)
- Marrow adipocytes, like brown and white adipocytes, are derived from mesenchymal stem cells. (wikipedia.org)
- Mesenchymal stem cells can differentiate into adipocytes, connective tissue, muscle or bone. (wikipedia.org)
- We investigated the ability of fetal mesenchymal stem cells (fMSCs) to differentiate into brown and white adipocytes and compared the expression of a number of marker genes and key regulatory factors. (qxmd.com)
- The formation of adipocytes, a process known as adipogenesis, has been extensively studied, but there remain major gaps in our knowledge: for example, the identities of many of the transcriptional regulators that are responsible for the differentiation of mesenchymal stem cells into adipocytes remain a mystery. (elifesciences.org)
- Experiments in our laboratory are currently devoted to developing CRISPR- and siRNA-based delivery particles that can beneficially alter gene expression in adipocytes, hepatocytes and other cell types. (umassmed.edu)
- These findings indicated that FPP might function as an endogenous PPARγ agonist and regulate gene expression in adipocytes. (biochemj.org)
- Here, we demonstrated that mice with a fat-specific KO of dicer develop a form of lipodystrophy that is characterized by loss of intra-abdominal and subcutaneous white fat, severe insulin resistance, and enlargement and "whitening" of interscapular brown fat. (nih.gov)
- (grantome.com)
- ligand class of insulin- sensitizers induces BAT functions in white adipocytes in mice and in culture. (grantome.com)
- show that drugs that target β3 adrenergic receptors cause white fat cells in mice to change into beige fat cells. (elifesciences.org)
- Maintaining adipocyte-specific expression of Lsd1 in transgenic mice preserves the pool of beige adipocytes in old mice. (pnas.org)
- Maintenance of beige adipocytes is mediated by the Lsd1 target gene peroxisome proliferator-activated receptor α (Ppara) and pharmacological activation of Ppara rescues the loss of beige adipocytes in Lsd1-KO mice. (pnas.org)
- Here, we show that the majority of the precursor and mature subcutaneous white adipocytes in adult C57Bl/6 mice are labeled by Prx1-Cre. (umassmed.edu)
- 24 or 48 h) on gene expression using real-time RT-PCR in 3 distinct models: N-1 hypothalamic neurons, 3T3-L1 adipocytes and male CD-1 mice. (karger.com)
- Systolic blood pressure was measured by radiotelemetry during week 16 of low-fat or high-fat feeding in Agt fl/fl and adipocyte angiotensinogen-deficient mice ( Agt aP2 ). (ahajournals.org)
- and R406 induce brown-like lipid morphology (arrows) in human primary adipocytes more prominently than BMP7. (gatech.edu)
- white, beige and brown adipocytes look different and mirror their different tasks in the highly plastic adipose tissue. (promocell.com)
- It has recently been shown that serotonin leads to fat accumulation in white adipose tissue (WAT). (ovid.com)
- The number and activity of brown adipocytes are linked to the ability of mammals to resist body fat accumulation. (diabetesjournals.org)
- on insulin signaling, we hypothesized that T-AG17 might Drugs that act on mitochondria have been used to promote inhibition of adipogenesis and/or adipocyte hyper- combat fat accumulation by forcing cells to use stored trophy. (deepdyve.com)
- The lipoinflammation-associated mechanisms are related to the function of adipocytes and macrophages present in the adipose tissue. (elsevier.es)
- In biology, adipose tissue , body fat , or simply fat is a loose connective tissue composed mostly of adipocytes . (wikipedia.org)
- white adipose tissue and brown adipose tissue are made of adipocytes, connective tissue, immune cells and stem cells. (promocell.com)
- In parallel, serotonin led to 3-6-fold reduction in the gene expression of brown adipocyte differentiation markers, that is, Prdm16 (positive regulatory domain 16), Bmp7 (bone morphogenic protein 7) and Pparγ (peroxisome-proliferator-activated receptor γ). (ovid.com)
- Necessity tests, using mature adipocyte-specific Prdm16 deletion strategies, demonstrated that adipocytes are required and are predominant source to generate Adrb3 -induced, but not cold-induced, beige adipocytes. (elifesciences.org)
- Therefore, PRDM16 is required in brown adipocytes to suppress skeletal muscle development. (upenn.edu)
- These data suggest that PRDM16 controls brown adipocyte versus skeletal muscle cell fate. (upenn.edu)
- A total of 101 proteins were exclusively quantified in brown adipocytes, and among these was ependymin-related protein 1 (EPDR1). (regionh.dk)
- Mitochondrial toxicity of indinavir, stavudine and zidovudine involves multiple cellular targets in white and brown adipocytes. (inserm.fr)
- RESULTS: In both cell types, all the treatments induced a severe defect of adipogenesis (low lipid content and decreased markers of adipogenic maturation: peroxisome proliferator-activated receptor [PPAR]gamma2 and aP2 but also uncoupling protein 1 in brown adipocytes) as well as altered mitochondrial function (decreased respiration rate and increased mitochondrial mass). (inserm.fr)
- With all the treatments, white adipocytes showed a decrease in the expression of mitochondrial and nuclear-DNA-encoded respiratory chain subunits (cytochrome c oxidase [CytOx]2 and CytOx4), whereas brown adipocytes maintained normal expression in accordance with their increase of the transcriptional factors of mitochondrial biogenesis nuclear respiratory factor 1 and PPARgamma coactivator (PGC)1-related cofactor PRC, but not PGC1alpha. (inserm.fr)
- Brown adipocytes express thermogenin (UCP-1), which catalyzes the re-entry of protons into the matrix, uncoupling the mitochondrial respiratory chain, and consequently reducing the ATP synthesis and generating heat. (gatech.edu)
- A role for estrogen-related receptor alpha in the control of mitochondrial fatty acid beta-oxidation during brown adipocyte differentiation. (qxmd.com)
- High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats. (biomedsearch.com)
- We showed that the expression of key adipocyte regulators and markers during differentiation is similar to that in other human and murine adipocyte models, including induction of PPARgamma2 and FABP4. (qxmd.com)
- Moreover, the addition of FPP up-regulated the mRNA expression levels of PPARγ target genes during adipocyte differentiation induction. (biochemj.org)
- malignant fat) develops into beige adipocytes remains obscure, largely because there is a lack of a good animal model for the induction of beige adipocytes from aWAT. (sciencemag.org)
- A cell line of mature human adipocytes was incubated with 50 μ g/mL lutein for 24 and 48 h, whereafter FD mRNA and protein expression were measured. (hindawi.com)
- Lutein significantly inhibited adipocyte FD mRNA expression and FD protein release into adipocyte culture supernatants. (hindawi.com)
- Genome-wide mRNA-seq expression profiling and ChIP-seq binding studies confirmed that TAF7L is required for activating adipocyte-specific genes via a dual mechanism wherein it interacts with PPARγ at enhancers and TBP/Pol II at core promoters. (elifesciences.org)
- Cultured WAT explants from humans and rats and 3T3-F442A adipocytes were rosiglitazone-treated before analyses of PDK2 and PDK4 mRNA and protein. (biomedsearch.com)
- White adipose tissue (WAT) , which stores excess energy and also has a role in regulating satiety through leptin secretion. (gatech.edu)
- Here we have investigated the role of the protein caveolin 1 (Cav1) and caveolae in the secretion of the white adipocyte hormone adiponectin. (bioscientifica.com)
- Using mouse primary subcutaneous adipocytes genetically depleted of Cav1, we show that the adiponectin secretion, stimulated either adrenergically or by insulin, is abrogated while basal (unstimulated) release of adiponectin is elevated. (bioscientifica.com)
- Adiponectin secretion is similarly affected in wildtype mouse and human adipocytes where the caveolae structure was chemically disrupted. (bioscientifica.com)
- However, PET scans have identified biologically active brown adipocytes in various locations under the skin in the supraclavicular region and around blood vessels and solid organs in adults ( Sacks and Symonds, 2013 ). (promocell.com)
- Together, these findings indicate the importance of miRNA processing in white and brown adipose tissue determination and provide a potential link between this process and HIV-related lipodystrophy. (nih.gov)
- In this study, we present evidence for high-fat diet (HFD)-induced emergence of brown-like adipocytes in white adipose tissue (WAT) of the spontaneously hypertensive rat (SHR). (biomedsearch.com)
- In this article, we provide a perspective on the effects of hypoxia on the function of white adipocytes and consider, in particular, whether hypoxia also occurs in brown adipose tissue (BAT). (frontiersin.org)
- Two different types of adipose tissue including white adipose tissue (WAT) and brown adipose tissue (BAT) have been widely studied. (diabetesjournals.org)
- White adipose tissue (WAT) is an organ distributed at several locations in the body and with an essential role in the regulation of energy homeostasis. (biochemj.org)
- Oleoylethanolamide (OEA) can inhibit feeding and stimulate lipolysis by activating peroxisome proliferator-activating receptor-α (PPARα) in white adipose tissue (WAT). (biologists.org)
- We discuss important considerations when investigating adrenoceptor function in adipose tissue or adipocytes. (diva-portal.org)
- Adipokines: inflammation and the pleiotropic role of white adipose tissue. (semanticscholar.org)
- Brown adipose tissue contains lots of tiny lipid (fat) droplets, compared to white adipose tissue, which contains a single drop of lipid. (gatech.edu)
- At the level of adipose tissue, systemic inflammation may be initiated by adipocytes dysfunction [ 2 ]. (hindawi.com)
- We studied the molecular mechanisms responsible for differential expression of PGC-1alpha in HIB1B (BAT) and 3T3-L1 white adipose tissue (WAT) precursor cell lines. (elsevier.com)
- Interestingly, marrow adipose tissue response to exercise approximates that of WAT exercise reduces both adipocyte size as well as MAT volume as quantified by MRI or μCT imaging of bone stained with the lipid binder osmium. (wikipedia.org)
- The two types of adipose tissue are white adipose tissue (WAT), which stores energy, and brown adipose tissue (BAT), which generates body heat. (wikipedia.org)
- Here we show that levels of the epigenetic eraser lysine-specific demethylase 1 (Lsd1) decrease in aging inguinal white adipose tissue concomitantly with beige fat cell decline. (pnas.org)
- In mammals, adipose tissue exists as mainly as two different types: white adipose tissue (WAT) 3 and brown adipose tissue (BAT). (pubmedcentralcanada.ca)
- Lipolysis and lipases in white adipose tissue - An update. (semanticscholar.org)
- In addition, the researchers found that SIRT1 must be present in POMC neurons for leptin to stimulate the remodeling of white adipose tissue into brown fat tissue, which "burns" fat to generate heat. (medindia.net)
- Here we report that TAF7L, a paralogue of TFIID subunit TAF7, is enriched in adipocytes and white fat tissue (WAT) in mouse. (elifesciences.org)
- White tissue, or white fat, is where energy is stored. (thenextweb.com)
- Mammals have two main subtypes of adipose tissue, white and brown. (upenn.edu)
- White adipose tissue is specialized for energy storage, whereas brown adipose expends chemical energy in the form of heat. (upenn.edu)
- PDC shares the same substrate, i.e., pyruvate, as glyceroneogenesis, a pathway controlling fatty acid release from white adipose tissue (WAT). (biomedsearch.com)
- In rodents, beige adipocytes occur in clusters surrounded by white adipocytes in subcutaneous fat, suggesting the reason for the neutral to beneficial effects of that tissue. (rockefeller.edu)
- Excess energy is mainly stored in white adipose tissue, resulting in overweight. (dife.de)
- Brown adipose tissue (in contrast to white adipose tissue) has a remarkable capacity to dissipate energy in the form of heat. (dife.de)
- Brown adipose tissue (BAT) or brown fat makes up the adipose organ together with white adipose tissue (or white fat). (wikipedia.org)
- In contrast to white adipocytes, which contain a single lipid droplet, brown adipocytes contain numerous smaller droplets and a much higher number of (iron-containing) mitochondria, which gives brown adipose tissue its brown appearance. (wikipedia.org)
- Brown fat also contains more capillaries than white fat, to supply the tissue with oxygen and nutrients and distribute the produced heat throughout the body. (wikipedia.org)
- However, it is largely unknown whether adipocyte hypertrophy per se might be sufficient to provoke insulin resistance in obese adipose tissue. (asm.org)
- white adipocytes not only store fat, but they also produce hormones that regulate energy homeostasis, food intake, and tissue regeneration. (promocell.com)
- White adipocyte tissue also has endocrine functions and releases hormones such as leptin, adiponectin, fatty acids, and TNF-α that regulate nutrient homeostasis, food intake, inflammation, cardiovascular activity, and tissue regeneration ( Medina-Gómez, 2016 ). (promocell.com)
- Until the past decade, researchers thought brown adipose tissue was only active in infants and young children, and that it later transformed into white adipocyte tissue with aging. (promocell.com)
- Also, excess white adipose tissue increases the risk factor of heart diseases and heart failure. (promocell.com)
- However, the mechanisms controlling the age-related transition of beige adipocytes to white adipocytes remain unclear. (pnas.org)
- In contrast, Adrb3 activation stimulates mature white adipocytes to convert into beige adipocytes. (elifesciences.org)
- on the other hand activates SRF activity by promoting MRTF-A movement into the nucleus, which leads to suppression of adipocyte genes and activation of vascular genes including smooth muscle (SM) actin, SM heavy chain myosin (SM- MHC) and SM22. (grantome.com)
- Using a combination of cellular, biochemical, genetic and genomic techniques, they show that TAF7L interacts with PPARγ, an important adipocyte transcriptional regulator at enhancer sites on the genome to increase the transcription of genes that are involved in adipogenesis. (elifesciences.org)
- In addition, we identified molecular markers that were highly enriched in beige adipocytes and conserved between bat aWAT and mouse sWAT, a set that included the genes Uqcrc1 and Letm1 . (sciencemag.org)
- VPA also induced the expression of CEBP αin 3T3-L1 adipocytes , but had no effect on other target genes, and TSA suppressed fiaf and socs-3 .Subsequently, CEBPα was overexpressed (24 h) or silenced using RNAi (24 and 48 h) in N-1 neurons. (karger.com)
- There are two major types of adipose, white that stores TGs and brown (BAT) that oxidizes them to produce heat. (grantome.com)
- Recent identification of active brown fat reserves in adult humans has re-stimulated interest in the role of brown adipocytes in energy homeostasis. (frontiersin.org)
- These findings suggest that TAF7L plays an integral role in adipocyte gene expression by targeting enhancers as a cofactor for PPARγ and promoters as a component of the core transcriptional machinery. (elifesciences.org)
- In the present study, we examine whether mevalonate metabolites activate PPARγ (peroxisome-proliferator-activated receptor γ), a ligand-dependent transcription factor playing a central role in adipocyte differentiation. (biochemj.org)
- Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser enzyme positively regulating differentiation and function of adipocytes. (pnas.org)
- Brown adipocytes are smaller than white ones, contain many mitochondria and several small lipid droplets. (promocell.com)
- Moreover, although BMP6-treated myoblasts can readily differentiate into brown adipocytes, serotonin interfered with this process. (ovid.com)
- In sharp contrast, few to no brown adipocytes or visceral white adipocytes are marked by Prx1-Cre. (umassmed.edu)
- Furthermore, CAP increased the expression of sirtuin-1 (SiRT-1 deacetylase) and PR domain protein 16 (PRDM-16-gene responsible for the molecular switch of white to brown fat) in WAT. (ahajournals.org)
- To better understand the development of beige adipocytes from mammalian WATs, especially aWAT, we induced beige adipocytes from bat aWAT and mouse sWAT by exposure to cold temperatures and analyzed their molecular signatures. (sciencemag.org)
- To address this question, we have employed the perforated patch current-clamp and cell-attached patch-clamp methods in isolated primary white fat adipocytes and their cellular model: 3T3-L1. (nottingham.ac.uk)
- METHODS: 3T3-F442A white and T37i brown adipocytes were exposed to stavudine (10 microM), zidovudine (1 microM) and indinavir (10 microM), alone or in combination. (inserm.fr)