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.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.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.Adipocytes, Brown: Fat cells with dark coloration due to the densely packed MITOCHONDRIA. They contain numerous small lipid droplets or vacuoles. Their stored lipids can be converted directly to energy as heat by the mitochondria.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.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.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.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.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.Phaeophyta: A division of predominantly marine EUKARYOTA, commonly known as brown algae, having CHROMATOPHORES containing carotenoid PIGMENTS, BIOLOGICAL. ALGINATES and phlorotannins occur widely in all major orders. They are considered the most highly evolved algae because of their well-developed multicellular organization and structural complexity.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.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.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.Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.Rats, Inbred BNCells, 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.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.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).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.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.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.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.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.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Cold Temperature: An absence of warmth or heat or a temperature notably below an accustomed norm.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.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.Sterol Esterase: An enzyme that catalyzes the hydrolysis of CHOLESTEROL ESTERS and some other sterol esters, to liberate cholesterol plus a fatty acid anion.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.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.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).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)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.Fatty 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)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.Mice, Inbred C57BLIsoproterenol: 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.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.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Hypoglycemic Agents: Substances which lower blood glucose levels.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.Phenylisopropyladenosine: N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.DioxolesCCAAT-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.Subcutaneous Fat: Fatty tissue under the SKIN through out the body.Body Temperature Regulation: The processes of heating and cooling that an organism uses to control its temperature.MethylglucosidesAdipokines: 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.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.PhosphoproteinsAdrenergic beta-3 Receptor Agonists: Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.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.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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Insulin Antagonists: Compounds which inhibit or antagonize the biosynthesis or action of insulin.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.Cystinyl Aminopeptidase: A zinc-containing sialoglycoprotein that is used to study aminopeptidase activity in the pathogenesis of hypertension. EC 3.4.11.3.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.TriglyceridesBrown Recluse Spider: A spider of the genus Loxosceles, found in the midwestern and other parts of the United States, which carries a hemolytic venom that produces local necrosis or ulceration.Kinetics: The rate dynamics in chemical or physical systems.Reverse 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.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)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.Trout: Various fish of the family SALMONIDAE, usually smaller than salmon. They are mostly restricted to cool clear freshwater. Some are anadromous. They are highly regarded for their handsome colors, rich well-flavored flesh, and gameness as an angling fish. The genera Salvelinus, Salmo, and ONCORHYNCHUS have been introduced virtually throughout the world.Mitochondria: 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)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.Glycerolphosphate DehydrogenaseFatty 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.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 KINASESRats, 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.Hormones, Ectopic: Hormones released from neoplasms or from other cells that are not the usual sources of hormones.Fatty Acid Synthases: Enzymes that catalyze the synthesis of FATTY ACIDS from acetyl-CoA and malonyl-CoA derivatives.Omentum: A double-layered fold of peritoneum that attaches the STOMACH to other organs in the ABDOMINAL CAVITY.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.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.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.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.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.Lipase: 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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Diet, High-Fat: Consumption of excessive DIETARY FATS.Sargassum: One of the largest genera of BROWN ALGAE, comprised of more than 150 species found in tropical, subtropical, and temperate zones of both hemispheres. Some species are attached (benthic) but most float in the open sea (pelagic). Sargassum provides a critical habitat for hundreds of species of FISHES; TURTLES; and INVERTEBRATES.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Acclimatization: Adaptation to a new environment or to a change in the old.Seaweed: Multicellular marine macroalgae including some members of red (RHODOPHYTA), green (CHLOROPHYTA), and brown (PHAEOPHYTA) algae. They are widely distributed in the ocean, occurring from the tide level to considerable depths, free-floating (planktonic) or anchored to the substratum (benthic). They lack a specialized vascular system but take up fluids, nutrients, and gases directly from the water. They contain CHLOROPHYLL and are photosynthetic, but some also contain other light-absorbing pigments. Many are of economic importance as FOOD, fertilizer, AGAR, potash, or source of IODINE.Fucus: A genus of BROWN ALGAE in the family Fucaceae. It is found in temperate, marine intertidal areas along rocky coasts and is a source of ALGINATES. Some species of Fucus are referred to as KELP.Hares: The genus Lepus, in the family Leporidae, order LAGOMORPHA. Hares are born above ground, fully furred, and with their eyes and ears open. In contrast with RABBITS, hares have 24 chromosome pairs.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.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.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.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.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.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.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.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.Uncoupling Agents: Chemical agents that uncouple oxidation from phosphorylation in the metabolic cycle so that ATP synthesis does not occur. Included here are those IONOPHORES that disrupt electron transfer by short-circuiting the proton gradient across mitochondrial membranes.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.ThiazolesPalmitic Acid: A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids.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.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.Adiposity: The amount of fat or lipid deposit at a site or an organ in the body, an indicator of body fat status.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.Sterol 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)Chromans: Benzopyrans saturated in the 2 and 3 positions.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.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.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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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.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.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.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.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)Laminaria: A genus of BROWN ALGAE in the family Laminariaceae. Dried pencil-like pieces may be inserted in the cervix where they swell as they absorb moisture, serving as osmotic dilators.Azo CompoundsNicotinamide 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).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.Oxygen Consumption: The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)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.HexosesCell Size: The quantity of volume or surface area of CELLS.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.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.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.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.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.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.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.Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.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.Blood Glucose: Glucose in blood.Deoxy SugarsCricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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.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.Chiroptera: Order of mammals whose members are adapted for flight. It includes bats, flying foxes, and fruit bats.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.Eating: The consumption of edible substances.Cell Transdifferentiation: A naturally occurring phenomenon where terminally differentiated cells dedifferentiate to the point where they can switch CELL LINEAGES. The cells then differentiate into other cell types.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.Hemiptera: A large order of insects characterized by having the mouth parts adapted to piercing or sucking. It is comprised of four suborders: HETEROPTERA, Auchenorrhyncha, Sternorrhyncha, and Coleorrhyncha.Propanolamines: AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.Triiodothyronine: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.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)Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.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.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.Lipoma: A benign tumor composed of fat cells (ADIPOCYTES). It can be surrounded by a thin layer of connective tissue (encapsulated), or diffuse without the capsule.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.Cell Compartmentation: A partitioning within cells due to the selectively permeable membranes which enclose each of the separate parts, e.g., mitochondria, lysosomes, etc.Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.Eye Color: Color of the iris.Palmitates: Salts and esters of the 16-carbon saturated monocarboxylic acid--palmitic acid.Subcutaneous Fat, Abdominal: Fatty tissue under the SKIN in the region of the ABDOMEN.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.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Real-Time Polymerase Chain Reaction: Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.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.

Expression of mitochondrial biogenesis-signaling factors in brown adipocytes is influenced specifically by 17beta-estradiol, testosterone, and progesterone. (1/125)

Control of mitochondrial biogenesis in brown adipose tissue (BAT), as part of the thermogenesis program, is a complex process that requires the integration of multiple transcription factors to orchestrate mitochondrial and nuclear gene expression. Despite the knowledge of the role of sex hormones on BAT physiology, little is known about the effect of these hormones on the mitochondrial biogenic program. The aim of this study was to determine the effect of testosterone, 17beta-estradiol, and progesterone on the expression of nuclear factors involved in the control of mitochondrial biogenesis and thermogenic function such as ppargamma, pgc1alpha, nrf1, gabpa, and tfam, and also an inhibitor of PI3K-Akt pathway, recently found to be involved in the control of mitochondrial recruitment (pten). For this purpose, an in vitro assay using cell-cultured brown adipocytes was used to address the role of steroid hormones, progesterone, testosterone, and 17beta-estradiol on the mRNA expression of these factors by real-time PCR. Thus 17beta-estradiol seemed to exert a dual effect, activating the PI3K-Akt pathway by inhibiting pten mRNA expression and also inhibiting nrf1 and tfam mRNA expression. Progesterone seemed to positively stimulate mitochondriogenesis and BAT differentiation by increasing the mRNA expression of the gabpa-tfam axis and ppargamma, respectively, but also exerted a negative output by increasing pten mRNA levels. Finally, testosterone inhibited the transcription of pgc1alpha, the master factor involved in UCP1 expression and mitochondrial biogenesis. In conclusion, our results support the idea that sex hormones have direct effects on different mediators of the mitochondriogenesis program.  (+info)

Bidirectional Ca2+ coupling of mitochondria with the endoplasmic reticulum and regulation of multimodal Ca2+ entries in rat brown adipocytes. (2/125)

How the endoplasmic reticulum (ER) and mitochondria communicate with each other and how they regulate plasmalemmal Ca(2+) entry were studied in cultured rat brown adipocytes. Cytoplasmic Ca(2+) or Mg(2+) and mitochondrial membrane potential were measured by fluorometry. The sustained component of rises in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) produced by thapsigargin was abolished by removing extracellular Ca(2+), depressed by depleting extracellular Na(+), and enhanced by raising extracellular pH. FCCP, dinitrophenol, and rotenone caused bi- or triphasic rises in [Ca(2+)](i), in which the first phase was accompanied by mitochondrial depolarization. The FCCP-induced first phase was partially inhibited by oligomycin but not by ruthenium red, cyclosporine A, U-73122, a Ca(2+)-free EGTA solution, and an Na(+)-free solution. The FCCP-induced second phase paralleling mitochondrial repolarization was partially blocked by removing extracellular Ca(2+) and fully blocked by oligomycin but not by thapsigargin or an Na(+)-deficient solution, was accompanied by a rise in cytoplasmic Mg(2+) concentration, and was summated with a high pH-induced rise in [Ca(2+)](i), whereas the extracellular Ca(2+)-independent component was blocked by U-73122 and cyclopiazonic acid. The FCCP-induced third phase was blocked by removing Ca(2+) but not by thapsigargin, depressed by decreasing Na(+), and enhanced by raising pH. Cyclopiazonic acid-evoked rises in [Ca(2+)](i) in a Ca(2+)-free solution were depressed after FCCP actions. Thus mitochondrial uncoupling causes Ca(2+) release, activating Ca(2+) release from the ER and store-operated Ca(2+) entry, and directly elicits a novel plasmalemmal Ca(2+) entry, whereas Ca(2+) release from the ER activates Ca(2+) accumulation in, or release from, mitochondria, indicating bidirectional mitochondria-ER couplings in rat brown adipocytes.  (+info)

Hypoxic adipocytes pattern early heterotopic bone formation. (3/125)

The factors contributing to heterotopic ossification, the formation of bone in abnormal soft-tissue locations, are beginning to emerge, but little is known about microenvironmental conditions promoting this often devastating disease. Using a murine model in which endochondral bone formation is triggered in muscle by bone morphogenetic protein 2 (BMP2), we studied changes near the site of injection of BMP2-expressing cells. As early as 24 hours later, brown adipocytes began accumulating in the lesional area. These cells stained positively for pimonidazole and therefore generated hypoxic stress within the target tissue, a prerequisite for the differentiation of stem cells to chondrocytes and subsequent heterotopic bone formation. We propose that aberrant expression of BMPs in soft tissue stimulates production of brown adipocytes, which drive the early steps of heterotopic endochondral ossification by lowering oxygen tension in adjacent tissue, creating the correct environment for chondrogenesis. Results in misty gray lean mutant mice not producing brown fat suggest that white adipocytes convert into fat-oxidizing cells when brown adipocytes are unavailable, providing a compensatory mechanism for generation of a hypoxic microenvironment. Manipulation of the transcriptional control of adipocyte fate in local soft-tissue environments may offer a means to prevent or treat development of bone in extraskeletal sites.  (+info)

Transcriptional control of brown fat determination by PRDM16. (4/125)

Brown fat cells are specialized to dissipate energy and can counteract obesity; however, the transcriptional basis of their determination is largely unknown. We show here that the zinc-finger protein PRDM16 is highly enriched in brown fat cells compared to white fat cells. When expressed in white fat cell progenitors, PRDM16 activates a robust brown fat phenotype including induction of PGC-1alpha, UCP1, and type 2 deiodinase (Dio2) expression and a remarkable increase in uncoupled respiration. Transgenic expression of PRDM16 at physiological levels in white fat depots stimulates the formation of brown fat cells. Depletion of PRDM16 through shRNA expression in brown fat cells causes a near total loss of the brown characteristics. PRDM16 activates brown fat cell identity at least in part by simultaneously activating PGC-1alpha and PGC-1beta through direct protein binding. These data indicate that PRDM16 can control the determination of brown fat fate.  (+info)

Ca(2+) -independent effects of BAPTA and EGTA on single-channel Cl(-) currents in brown adipocytes. (5/125)

The Cl(-) channels of brown adipocytes electrophysiologically resemble outwardly rectifying Cl(-) channels (ORCC). To study tentative Ca(2+) regulation of these channels, we attempted to control Ca(2+) levels at the cytoplasmic side of the inside-out membrane patches with Ca(2+)-chelating agents. However, we found that the commonly used Ca(2+)-chelators EGTA and BAPTA by themselves influenced the Cl(-) channel currents, unrelated to their calcium chelating effects. Consequently, in this report we delineate effects of Ca(2+)-chelators (acting from the cytoplasmic side) on the single Cl(-) channel currents in patch-clamp experiments. Using fixed (1-2 mM) concentrations of chelators, two types of Cl(-) channels were identified, as discriminated by their reaction to the Ca(2+)-chelators and by their conductance: true-blockage channels (31 pS) and quasi-blockage channels (52 pS). In true-blockage channels, EGTA and BAPTA inhibited channel activity in a classical flickery type manner. In quasi-blockage channels, chelators significantly shortened the duration of individual openings, as in a flickering block, but the overall channel activity tended to increase. This dual effect of mean open time decrease accompanied by a tendency of open probability to increase we termed a quasi-blockage. Despite the complications due to the chelators as such, we could detect a moderate inhibitory effect of Ca(2+). The anionic classical Cl(-) channel blockers DIDS and SITS could mimic the true/quasi blockage of EGTA and BAPTA. It was concluded that at least in this experimental system, standard techniques for Ca(2+) level control in themselves could fundamentally affect the behaviour of Cl(-) channels.  (+info)

Insulin resistance induced by tumor necrosis factor-alpha in myocytes and brown adipocytes. (6/125)

Insulin resistance is an important contributor to the pathogenesis of type 2 diabetes, and obesity is a risk factor for its development, in part because adipose tissue secretes proteins, called adipokines, that may influence insulin sensitivity. Among these molecules, tumor necrosis factor (TNF)-alpha has been proposed as a link between obesity and insulin resistance because TNF-alpha is overexpressed in adipose tissues of obese animals and humans, and obese mice lacking either TNF-alpha or its receptor show protection against developing insulin resistance. Direct exposure to TNF-alpha induces a state of insulin resistance in terms of glucose uptake in myocytes and brown adipocytes because of the activation of proinflammatory pathways that impair insulin signaling at the level of the insulin receptor substrate (IRS) proteins. In this regard, the Ser(307) residue in IRS-1 has been identified as a site for the inhibitory effects of TNF-alpha in myotubes, with p38 mitogen-activated protein kinase and inhibitor kB kinase being involved in the phosphorylation of this residue. Conversely, Ser phosphorylation of IRS-2 mediated by TNF-alpha activation of mitogen-activated protein kinase was the mechanism found in brown adipocytes. Protein-Tyr phosphatase (PTP)1B acts as a physiological, negative regulator of insulin signaling by dephosphorylating the phosphotyrosine residues of the insulin receptor and IRS-1, and PTP1B expression is increased in muscle and white adipose tissue of obese and diabetic humans and rodents. Moreover, up-regulation of PTP1B expression was recently found in cells treated with TNF-alpha Accordingly, myocytes and primary brown adipocytes deficient in PTP1B are protected against insulin resistance induced by this cytokine. Furthermore, down-regulation of PTP1B activity is possible by the use of pharmacological agonists of nuclear receptors that restore insulin sensitivity in the presence of TNF-alpha. In conclusion, the lack of PTP1B in muscle and brown adipocytes increases insulin sensitivity and glucose uptake and could confer protection against insulin resistance induced by adipokines.  (+info)

Nutritional and hormonal regulation of uncoupling protein gene expression in rat adipocytes. (7/125)

Nutritional and hormonal regulation of the expression of uncoupling protein (UCP)-1, -2, and -3 mRNA and protein was investigated in primary cultured adipocytes of rats. The UCP-1, -2, -3 mRNA and protein induction in the adipocytes reached maximal levels at 4 h in the presence of glucose with or without insulin. Moreover, the UCP induction was accelerated by triiodothyronine (T3) or epinephrine, and reached a maximum at 2 h. It appeared that the induction of UCP mRNA and protein was rapid. UCP-1 mRNA expression was stimulated by the presence of T3 or epinephrine in the culture medium. UCP-2 mRNA expression was more markedly increased by glucose, unsaturated fatty acids, insulin and T3 than UCP-1 or -3 mRNA expression. UCP-3 expression was more markedly increased by epinephrine than by T3. The protein expression of the UCPs was induced by glucose and the hormones nearly parallel to the UCP mRNA expression. Thus, UCP-2 expression appears to be stimulated by energy sources such as glucose and fat, and by regulators of thermogenesis and basal metabolic rate such as T3 and insulin, in contrast to UCP-1 and -3 expression.  (+info)

Forkhead transcription factor FoxO1 in adipose tissue regulates energy storage and expenditure. (8/125)

OBJECTIVE: Adipose tissue serves as an integrator of various physiological pathways, energy balance, and glucose homeostasis. Forkhead box-containing protein O subfamily (FoxO) 1 mediates insulin action at the transcriptional level. However, physiological roles of FoxO1 in adipose tissue remain unclear. RESEARCH DESIGN AND METHODS: In the present study, we generated adipose tissue-specific FoxO1 transgenic mice (adipocyte protein 2 [aP(2)]-FLAG-Delta 256) using an aP(2) promoter/enhancer and a mutant FoxO1 (FLAG Delta 256) in which the carboxyl terminal transactivation domain was deleted. Using these mice, we analyzed the effects of the overexpression of FLAG Delta 256 on glucose metabolism and energy homeostasis. RESULTS: The aP(2)-FLAG-Delta 256 mice showed improved glucose tolerance and insulin sensitivity accompanied with smaller-sized adipocytes and increased adiponectin (adipoq) and Glut 4 (Slc2a4) and decreased tumor necrosis factor alpha (Tnf) and chemokine (C-C motif) receptor 2 (Ccr2) gene expression levels in white adipose tissue (WAT) under a high-fat diet. Furthermore, the aP(2)-FLAG-Delta 256 mice had increased oxygen consumption accompanied with increased expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1 alpha protein and uncoupling protein (UCP)-1 (Ucp1), UCP-2 (Ucp2), and beta 3-AR (Adrb3) in brown adipose tissue (BAT). Overexpression of FLAG Delta 256 in T37i cells, which are derived from the hibernoma of SV40 large T antigen transgenic mice, increased expression of PGC-1 alpha protein and Ucp1. Furthermore, knockdown of endogenous FoxO1 in T37i cells increased Pgc1 alpha (Ppargc1a), Pgc1 beta (Ppargc1b), Ucp1, and Adrb3 gene expression. CONCLUSIONS: These data suggest that FoxO1 modulates energy homeostasis in WAT and BAT through regulation of adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake.  (+info)

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As a prototypical second messenger, cAMP is involved in the regulation of multiple cell functions. cAMP has a well established inhibitory effect on cell proliferation in smooth muscle and epithelial cell types. However, there is accumulating evidence also for stimulatory effect on proliferation, mainly in endocrine cell types.. Mechanisms mediating the cAMP stimulatory effect are not well studied. cAMP, produced via β1-adrenoceptor activation, promotes cell proliferation in brown preadipocytes. Due to the importance of brown adipose tissue in energy metabolism and its implication in the treatment of obesity and type II diabetes, understanding the mechanisms of tissue recruitment has clinical implication for the treatment of these metabolic syndromes.. We found that the Erk1/2 family of MAPK, often involved in regulation of cell proliferation, can be activated in response to the stimulation of G protein-coupled receptors, including adrenergic receptors (α1-, α2-, β1- and β3-Adrenoceptors) ...
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b3-Adrenergic receptors (b3-ARs) are expressed predominantly on white and brown adipocytes, and acute treatment of mice with CL 316,243, a potent and highly selective b3-AR agonist, produces a 2-fold increase in energy expenditure, a 50-100-fold increase in insulin levels, and a 40-50% reduction in food intake. [5] ...
Background Brown adipocytes are specialised in dissipating energy through adaptive thermogenesis, whereas white adipocytes are specialised in energy storage. These essentially opposite functions are possible for two reasons relating to mitochondria, namely expression of uncoupling protein 1 (UCP1) and a remarkably higher mitochondrial abundance in brown adipocytes. Methodology/Principal Findings Here we report a comprehensive characterisation of gene expression linked to mitochondrial DNA replication, transcription and function during white and brown fat cell differentiation in vitro as well as in white and brown fat, brown adipose tissue fractions and in selected adipose tissues during cold exposure. We find a massive induction of the majority of such genes during brown adipocyte differentiation and recruitment, e.g. of the mitochondrial transcription factors A (Tfam) and B2 (Tfb2m), whereas only a subset of the same genes were induced during white adipose conversion. In addition, PR domain containing
Much of the current excitement in the obesity field stems from recent observations highlighting that, even as adults, we have the ability to generate brown fat cells in response to cold exposure. Unlike white fat cells that mostly just store fat, brown adipocytes keep us warm by burning fat at a high rate," said Dr. Philipp Scherer, Director of the Touchstone Center for Diabetes Research at UT Southwestern and senior author of the study available online at Nature Medicine.. While generation of brown fat cells previously was thought to be mostly relevant for rodents and human infants, Dr. Scherer said, current evidence points to the observation that adults also generate these cells when exposed to cold.. Brown fat cells in adults tend to be randomly interspersed in subcutaneous white fat, with a trend toward increased accumulation in the upper chest and neck areas. In general, brown fat tissue makes up just a small percentage of total body fat mass.. The Touchstone Centers staff devotes its ...
Brown adipose tissue (BAT), as the main site of adaptive thermogenesis, exerts beneficial metabolic effects on obesity and insulin resistance. BAT has been previously assumed to contain a homogeneous population of brown adipocytes. Utilizing multiple mouse models capable of genetically labeling different cellular populations, as well as single-cell RNA sequencing and 3D tissue profiling, we discovered a brown adipocyte subpopulation with low thermogenic activity coexisting with the classical high-thermogenic brown adipocytes within the BAT. Compared with the high-thermogenic brown adipocytes, these low-thermogenic brown adipocytes had substantially lower Ucp1 and Adipoq expression, larger lipid droplets, and lower mitochondrial content. Functional analyses showed that, unlike the high-thermogenic brown adipocytes, the low-thermogenic brown adipocytes have markedly lower basal mitochondrial respiration, and they are specialized in fatty acid uptake. Upon changes in environmental temperature, the ...
Brown adipose tissue (BAT), as the main site of adaptive thermogenesis, exerts beneficial metabolic effects on obesity and insulin resistance. BAT has been previously assumed to contain a homogeneous population of brown adipocytes. Utilizing multiple mouse models capable of genetically labeling different cellular populations, as well as single-cell RNA sequencing and 3D tissue profiling, we discovered a brown adipocyte subpopulation with low thermogenic activity coexisting with the classical high-thermogenic brown adipocytes within the BAT. Compared with the high-thermogenic brown adipocytes, these low-thermogenic brown adipocytes had substantially lower Ucp1 and Adipoq expression, larger lipid droplets, and lower mitochondrial content. Functional analyses showed that, unlike the high-thermogenic brown adipocytes, the low-thermogenic brown adipocytes have markedly lower basal mitochondrial respiration, and they are specialized in fatty acid uptake. Upon changes in environmental temperature, the ...
Yale scientists uncover how a molecular process in the brain that known to control eating transforms white fat into brown fat, impacting how much energy we burn and how much weight we can lose.. The results are published in the October 9 issue of the journal Cell.. Obesity is a rising global epidemic. Excess fatty tissue is a major risk factor for type 2 diabetes, cardiovascular disease, hypertension, neurological disorders, and cancer. People become overweight and obese when energy intake exceeds energy expenditure, and excess calories are stored in the adipose tissues. The adipose organ is made up of both white and brown fat. While white fat primarily stores energy as triglycerides, brown fat dissipates chemical energy as heat. The more brown fat you have, the more weight you can lose.. It has previously been shown that energy-storing white fat has the capacity to transform into energy-burning "brown-like" fat. In this new study, researchers from the Yale Program in Integrative Cell Signaling ...
TY - GEN. T1 - N-Acetyltransferase 8-like regulates lipid metabolism in brown adipocytes. AU - Bogner-Strauß, Juliane Gertrude. AU - Pelzmann, Helmut Josef. PY - 2013. Y1 - 2013. M3 - Conference contribution. SP - 15. EP - 15. BT - 3rd Scientific Retreat of the DK-Metabolic and Cardiovascular Disease. PB - .. ER - ...
Islands of brown fat can occur in many different places in the body. You may be able to appreciate a bit of extra pinkness to these cells, in addition to the vacuoles. You are seeing the protein-rich mitochondria. In this section, you cannot really tell where the cell borders are. But the vacuoles make the brown fat clear. ...
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Recent research may help develop pharmaceuticals that activate brown fat - thus making a difference for people suffering from diabetes and obesity.
If anybody has done their second semester at George brown or any other college please let me know. I am interested in what their second semester looked liked.
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Finally, at long last, the Browns have a date to name their quarterback. Decision day is Tuesday for Brian Hoyer and Johnny Manziel.
im 16 and i was supposed to start my period a couple weeks ago and i never did now i am spotting brown blood i was wondering if anyone could tell me what that means.
Expecting mothers often worry about all the different changes they go through during pregnancy, especially the events that seem abnormal to them. One thing that
Members PRDM1 PRDM2 PRDM3 PRDM4 PRDM5 PRDM6 PRDM7 PRDM8 PRDM9 PRDM10 PRDM11 PRDM12 PRDM13 PRDM14 PRDM15 PRDM16 Pathology PRDM1 Variants (...)
Im a big believer in the mindset that youve got to measure it to manage it. If you cant measure something, its very difficult to manage that something
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I fell off the Obagi bandwagon years ago. Huge mistake, but my life had taken so many turns that skin care was not a priority:...
Im 56, period started last thrusday, brown spotting and then bleeding, still bleeding lightly, over 5 years had none,is it normal, visiting my doc only Dec. 21, 2011 Thank you
In this chapter, pharmacologic agents are grouped according to the preferred practice patterns as listed originally in Chapter 6 of the Guide to Physical Therapist Practice, 2nd edition (revised).1 For each preferred practice pattern, medications that specifically address cardiovascular or pulmonary problems will be discussed as they relate to that practice pattern. It is, of course, not possible to describe all medications that might be related to each pattern. For example, medications used to control infection, treat cancer, and so forth, may help improve the patients overall health, thereby helping the patient to participate in aerobic conditioning, respiratory exercises, and other activities that will ultimately lead to better cardiovascular and pulmonary function. This chapter, however, will focus only on the medications that directly affect the heart, circulation, or lungs and describe how these medications relate to the physical therapy interventions described in the preferred practice ...
Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a phytol-derived branched-chain fatty acid present in dietary products. Phytanic acid increased uncoupling protein-1 (UCP1) mRNA expression in brown adipocytes differentiated in culture. Phytanic acid induced the expression of the UCP1 gene promoter, which was enhanced by co-transfection with a retinoid X receptor (RXR) expression vector but not with other expression vectors driving peroxisome proliferator-activated receptor (PPAR) α, PPARγ or a form of RXR devoid of ligand-dependent sensitivity. The effect of phytanic acid on the UCP1 gene required the 5′ enhancer region of the gene and the effects of phytanic acid were mediated in an additive manner by three binding sites for RXR. Moreover, phytanic acid activates brown adipocyte differentiation: long-term exposure of brown preadipocytes to phytanic acid promoted the acquisition of the brown adipocyte morphology and caused a co-ordinate induction of the mRNAs for gene markers of ...
TY - JOUR. T1 - Complementary roles of estrogen-related receptors in brown adipocyte thermogenic function. AU - Gantner, Marin L.. AU - Hazen, Bethany C.. AU - Eury, Elodie. AU - Brown, Erin L.. AU - Kralli, Anastasia. PY - 2016/12/1. Y1 - 2016/12/1. N2 - Brown adipose tissue (BAT) thermogenesis relies on a high abundance of mitochondria and the unique expression of the mitochondrial Uncoupling Protein 1 (UCP1), which uncouples substrate oxidation from ATP synthesis. Adrenergic stimulation of brown adipocytes activates UCP1-mediated thermogenesis; it also induces the expression of Ucp1 and other genes important for thermogenesis, thereby endowing adipocytes with higher oxidative and uncoupling capacities. Adipocyte mitochondrial biogenesis and oxidative capacity are controlled by multiple transcription factors, including the estrogen-related receptor (ERR)β. Whole-body ERRβ knockout mice show decreased BAT mitochondrial content and oxidative function but normal induction of Ucp1 in response to ...
Posted on 08/06/2012 1:46:58 AM PDT by neverdem. Columbia University Medical Center (CUMC) researchers have identified a mechanism that can give energy-storing white fat some of the beneficial characteristics of energy-burning brown fat. The findings, based on studies of mice and of human fat tissue, could lead to new strategies for treating obesity and type 2 diabetes. The study was published August 2 in the online edition of the journal Cell. Humans have two types of fat tissue: white fat, which stores excess energy in the form of triglycerides, and brown fat, which is highly efficient at dissipating stored energy as heat. Newborns have a relative abundance of brown fat, as protection against exposure to cold temperatures. In adults, however, almost all excess energy is stored as white fat. Turning white fat into brown fat is an appealing therapeutic approach to staunching the obesity epidemic, but it has been difficult to do so in a safe and effective way, said study leader Domenico Accili, ...
Researchers at UCSF have identified the lynchpin that activates brown fat cells, which burn fat molecules instead of storing them, making them the focus of pharmaceutical research aimed at fighting obesity.
Researchers at UCSF have identified the lynchpin that activates brown fat cells, which burn fat molecules instead of storing them, making them the focus of pharmaceutical research aimed at fighting obesity.
Adipose tissue is broadly divided into brown and white varieties. Brown fat cells express high levels of thermogenic genes and help maintain body heat by burning calories. Beige fat cells function similarly, but they are not of the brown fat cell lineage. Rather, they develop in white fat, the tissue that we typically think of as "fat." White fat cells are involved in whole-body energy homeostasis and lipid storage and are found both under the skin and in the abdomen, where they are known as visceral adipose tissue (VAT). It is this type of fat that can help detect and eliminate pathogens as well as maintain immune homeostasis in the gut.. https://www.the-scientist.com/features/belly-fat-has-a-role-to-play-in-fighting-infections-64802. ...
Unlike its fluffy cousin white fat, brown fat is a substance we want for its thermogenic properties. Learn more about this metabolic adipose tissue.
Until the discovery of UCP2, UCP3 and a plant UCP in 1997, the brown fat UCP (UCP1), represented a very specific type of protein. UCP1 is uniquely present in brown adipocytes, and its function is to create a fatty acid-activated uncoupling of respiration. UCP1 is expressed at a very high level in brown adipocytes, where it may account for up to 4% of total protein and 8% of mitochondrial protein. The reason why UCP1 is present at a high level is unknown, but it suggests that a rapid and full uncoupling of respiration leading to a marked thermogenesis requires a large number of UCP1 molecules, with the activity of each molecule probably being weak. Physiological, pharmacological, biochemical, and genetic studies established the role of UCP1 in uncoupling of respiration and adaptive thermogenesis. Cold exposure of rodents is the most illustrative way of UCP1 induction. This depends on many hormones such as the thyroid hormones, but many studies based on the use of drugs activating ...
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Irisin can help in transforming white fat cells into brown ones. So what? The point is that brown fat cells are typically found in small amounts in adults while theyre common in babies and children. The role of brown fat tissues is to promote energy burning while fat cells promote fat storage! So when you exercise, your body secretes Irisin hormone, transforms white fat into metabolically active brown fat, consequently, increasing fat burning for longer! ...
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There is much interest in being able to harvest the power of brown fat in humans to combat obesity and accompanying metabolic disease.
MR imaging has been used to successfully identify calorie-burning brown adipose tissue (BAT), and the results could be a major step forward in finding therapies against diabetes and obesity, according
Brown Said Stimulus Would "Go a Long Way Toward Putting Americans Back to Work." "This bill will go a long way toward putting Americans back to work and our economy back on track, Mr. Brown said. It includes critical infrastructure funds that provide immediate job creation while driving long-term economic development. It also creates a new generation of green jobs that will revive our nations manufacturing base while reducing our dependence on foreign oil." (Tom Troy, "Brown, Kaptur Back Stimulus; GOPs Voinovich Rejects It," The [Toledo, OH] Blade, 2/12/09 ...
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After 14 years of being beaten every way imaginable, nobody is spitting on the Browns defense anymore.The Browns carry the third-ranked defense into their Thursday night game against the Bills. They are fourth against the run, ninth against the pa
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Heres why brown discharge happens when youre not pregnant - including when it might be implantation bleeding - and when you may need to see your doctor.
Near the end of the menstrual period, the blood can turn a dark brown or black, which WebMD states is common and not cause for alarm. What To Expect warns that brown discharge can also be an early...
Hello ,this is embarrassing but this has been going on for quite some time. My stools are almost always a reddish brown color never the usual darker brown.This has been going on so long I cant even re...
... , is a pulmonologist at National Jewish Health. Dr. Brown serves as Vice Chair of the Department of Medicine Clinical Affairs.
... Rihanna and Chris Brown have had a ridiculously hard time staying apart these past few years.
Is it normal to have brown discharge after your period - Is it normal to have brown discharge after your period? Common. That should not represent a problem. It is pretty common.
My first look out the window this morning was to startle the brown thrasher.I was so happy to see him.It was this same day last year they arrived.He is larger than a robin & a beautiful rusty brown color,his eyes which are yellowish-orange looked directly at me ...
Wu, Jun; Cohen, Paul; Spiegelman, Bruce M. (2013-02-01). "Adaptive thermogenesis in adipocytes: is beige the new brown?". Genes ... MAT, by its "specific marrow location, and its adipocyte origin from at least LepR+ marrow MSC is separated from non-bone fat ... Marrow adipocytes are difficult to isolate and quantify because they are interspersed with bony and hematopoietic elements. ... Krings, A.; Rahman, S.; Huang, S.; Lu, Y.; Czernik, P. J.; Lecka-Czernik, B. (February 2012). "Bone marrow fat has brown ...
McInnes KJ, Brown KA, Hunger NI, Simpson ER (August 2011). "Regulation of LKB1 expression by sex hormones in adipocytes". Int J ... Brown KA, McInnes KJ, Takagi K, Ono K, Hunger NI, Wang L, Sasano H, Simpson ER (November 2011). "LKB1 expression is inhibited ... Testosterone and DHT treatment of murine 3T3-L1 or human SGBS adipocytes for 24 h significantly decreased the mRNA expression ...
"ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes". Biochimica et Biophysica Acta. 1801 (4): 421-9. doi: ... Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS (Oct 1993). "SREBP-1, a basic-helix-loop-helix- ... Brown MS, Goldstein JL (May 1997). "The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound ... Brown MS, Goldstein JL (Sep 1999). "A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood ...
... in brown adipocytes". Journal of Cellular Physiology. 218 (2): 444-449. doi:10.1002/jcp.21621. PMID 18937285. Hu, Z; Shen, WJ; ...
PLIN4 is a member of the perilipin family, a group of proteins that coat lipid droplets in adipocytes, the adipose tissue cells ... Soenen S, Mariman EC, Vogels N, Bouwman FG, den Hoed M, Brown L, Westerterp-Plantenga MS (March 2009). "Relationship between ... PLIN4 coats lipid droplets in adipocytes to protect them from lipases. The PLIN4 gene may be associated with insulin resistance ... It is highly expressed in white adipose tissue, with lower expression in heart, skeletal muscle, and brown adipose tissue. ...
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, ...
Yabe D, Brown MS, Goldstein JL (Oct 2002). "Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export ... Li J, Takaishi K, Cook W, McCorkle SK, Unger RH (Aug 2003). "Insig-1 "brakes" lipogenesis in adipocytes and inhibits ... Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, Goldstein JL, Brown MS (Aug 2002). "Crucial step in cholesterol ... Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, Goldstein JL, Brown MS (Aug 2002). "Crucial step in cholesterol ...
"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. ... A 2016 in vitro study of white and brown fat cell tissue found dose-related upregulation of a protein called UCP1 that ... Park A (April 8, 2009). "Brown Fat: A Fat That Helps You Lose Weight?". Health & Family. Time Magazine. Retrieved January 12, ...
April 2014). "Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice". Cell Metabolism. ... "Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers". Genes & Development. 29 (1): 7-22. doi: ...
Aug 2015). "FTO Obesity Variant Circuitry and Adipocyte Browning in Humans". New England Journal of Medicine. 373: 895-907. doi ...
"FTO Obesity Variant Circuitry and Adipocyte Browning in Humans". The New England Journal of Medicine. 373: 895-907. doi:10.1056 ... this single nucleotide alteration promoted a shift from energy-dissipating beige adipocytes to energy-storing white adipocytes ... and that there is a pathway for adipocyte thermoregulation which involves the proteine ARID5B, the single-nucleotide variant ... Another study found indications that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte ...
... a phenotype distinguishing brown adipocytes from interscapular brown adipose tissue and white adipose tissue". The Journal of ... Browning of WAT, also referred to as "beiging", occurs when adipocytes within WAT depots develop features of BAT. Beige ... Lo, KA; Sun, L (2013). "Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes". Bioscience ... Brown fat or brown adipose tissue is a specialized form of adipose tissue in humans and other mammals. It is located mainly ...
"Arotinolol is a weak partial agonist on beta 3-adrenergic receptors in brown adipocytes". Can J Physiol Pharmacol. 79 (7): 585- ... Markedly Increase Regional Blood Flow in the Brown Adipose Tissue in Anesthetized Rats". Japanese Circulation Journal. 56 (9): ...
"Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages". ... Firstly, it is expressed in brown adipose precursors. However, its expression is limited to brown and not white adipose ...
October 2005). "The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes". ...
"Beta 3-adrenergic receptor-mediated lipolysis and oxygen consumption in brown adipocytes from cynomolgus monkeys". J. Clin. ... "Brown adipose tissue, beta 3-adrenergic receptors, and obesity". Annu. Rev. Med. 48. pp. 307-16. "Archived copy". Archived from ...
Melanin: It is brown in color and present in the basal layer of the epidermis. Melanoid: It resembles melanin but is present ... 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 ... Liu, J., Kim, D., Brown, L., Madsen, T., Bouchard, G. F. "Comparison of Human, Porcine and Rodent Wound Healing With New ...
"Functional studies of the first selective β3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes". Mol. Pharmacol ...
"Functional studies of the first selective β3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes". Mol. Pharmacol ... Their role in gallbladder physiology is unknown, but they are thought to play a role in lipolysis and thermogenesis in brown ... relationship with the atypical receptor of adipocytes". EMBO J. 10 (12): 3721-7. PMC 453106 . PMID 1718744. Emorine LJ, Marullo ...
A. M. Lands; A. Arnold; J. P. McAuliff; F. P. Luduena; T. G. Brown (1967). "Differentiation of receptor systems activated by ... Johan Zaagsma; Stefan R. Nahorski (1990). "Is the adipocyte β-adrenoceptor a prototype of the recently cloned β3-adrenoceptor ... above all in adipocytes. After premonitions for example in the work of the Portuguese pharmacologist Serafim Guimarães, α- ...
"Functional studies of the first selective beta 3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes". Molecular ... ISBN 0-87893-725-0. Zhao TJ, Sakata I, Li RL, Liang G, Richardson JA, Brown MS, et al. (Sep 2010). "Ghrelin secretion ... Dec 1997). "Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte ...
... acts as a transcription coregulator that controls the development of brown adipocytes in brown adipose tissue. ... showing that PRDM16 activity is important in determining brown adipose fate. Brown adipocytes consist of densely packed ... The activity of PRDM16 in white adipose tissue leads to the production of brown fat-like adipocytes within white adipose tissue ... PRDM16 activates brown fat cell identity and can control the determination of brown adipose fate. A knock-out of PRDM16 in mice ...
... stavudine and zidovudine involves multiple cellular targets in white and brown adipocytes". Antivir. Ther. (Lond.). 12 (6): 919 ... Fujita T, Brown C, Carlson EJ, et al. (2005). "Functional analysis of polymorphisms in the organic anion transporter, SLC22A6 ( ... in white fat cells but not brown fat cells. Since stavudine and zidovudine are OAT1 substrates, they may have similar effects ...
2010). "Transcriptional regulation of a brown adipocyte-specific gene, UCP1, by KLF11 and KLF15". Biochem. Biophys. Res. Commun ... "Overexpression of KLF15 in adipocytes of mice results in down-regulation of SCD1 expression in adipocytes and consequent ... Wade HE, Kobayashi S, Eaton ML, Jansen MS, Lobenhofer EK, Lupien M, Geistlinger TR, Zhu W, Nevins JR, Brown M, Otteson DC, ... The expression of the KLF15 gene is markedly up-regulated during the differentiation of 3T3-L1 preadipocytes into adipocytes. ...
... 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 ... "Melatonin enhances leptin expression by rat adipocytes in the presence of insulin". Am. J. Physiol. Endocrinol. Metab. 288 (4 ... "Dexamethasone stimulates leptin release from human adipocytes: unexpected inhibition by insulin". J. Cell. Biochem. 65 (2): 254 ...
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 ...
Indole Derivatives Isolated from Brown Alga Sargassum thunbergii Inhibit Adipogenesis through AMPK Activation in 3T3-L1 ... Keywords: anti-obesity effect; adipocyte; Sargassum thunbergii; indole derivatives anti-obesity effect; adipocyte; Sargassum ... We found that STC-1 and STC-5 resulted in non-toxic inhibition of the differentiation of 3T3-L1 adipocytes and thus selected ... Indole Derivatives Isolated from Brown Alga Sargassum thunbergii Inhibit Adipogenesis through AMPK Activation in 3T3-L1 ...
Comparative Secretome Analyses of Primary Murine White and Brown Adipocytes Reveal Novel Adipokines Asrar Ali Khan, Jenny ... The secretome of white and brown primary murine adipocytes, with and without stimulation with norepinephrine (NE), has been ... The results reported reveal a comprehensive catalogue of novel adipokines secreted from white and brown adipocytes and ... this study provides an archive of potential brown adipokines and biomarkers for activated brown fat. ...
Identification of human brown adipocyte markers. (a) Venn diagram of the overlapping genes enriched in human brown adipocytes, ... mouse classical brown adipocytes, and mouse beige adipocytes versus white adipocytes of the respective species by two-fold or ... P , 0.001, brown versus white adipocyte lines; *P , 0.05, **P , 0.01, ***P , 0.001, brown or white (as indicated) versus basal ... Isolation of clonal brown adipocytes from adult human BAT. (a) Representative Oil-Red-O staining of differentiated brown ...
... Author(s). Claussnitzer, Melina; Dankel, Simon N.; Kim, Kyoung- ... FTO Obesity Variant Circuitry and Adipocyte Browning in Humans ." N Engl J Med 373, no. 10 (September 3, 2015): 895-907. © 2015 ... adipocytes to energy-storing white adipocytes, with a reduction in mitochondrial thermogenesis by a factor of 5, as well as an ... Repair of the ARID5B motif by CRISPR-Cas9 editing of rs1421085 in primary adipocytes from a patient with the risk allele ...
... browning) and activation of existing brown adipocytes are currently being investigated as a me ... Recruitment of the brown-like phenotype in white adipocytes ( ... browning) and activation of existing brown adipocytes are ... on induction of browning in 3T3-L1 adipocytes. CBD enhanced expression of a core set of brown fat-specific marker genes (Ucp1, ... Increased expression of UCP1 and other brown fat-specific markers contributed to the browning of 3T3-L1 adipocytes possibly via ...
Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes. *View ORCID ProfileZhangsen ... Three-dimensional high-resolution imaging in brown adipocytes from cold-challenged mice revealed that defective ERAD led to the ... Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes. By Zhangsen Zhou, Mauricio ... Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes. By Zhangsen Zhou, Mauricio ...
C) Quantification of the percentage of LacZ+ brown adipocytes in the total brown adipocytes. n = 11 mice (10 weeks old); n = 5 ... B) Quantification of the percentage of LacZ+ brown adipocytes in the total brown adipocytes. n = 8 mice (6°C); 6 mice (24°C); 7 ... Brown adipocytes heterogeneously and dynamically express Adipoq. To better understand brown adipocyte dynamics in vivo, we used ... Compared with the LacZ+ brown adipocytes (Adipoq high-expressing), the LacZ- brown adipocytes had markedly lower mitochondrial ...
Compared with the high-thermogenic brown adipocytes, these low-thermogenic brown adipocytes had substantially lower Ucp1 and ... Functional analyses showed that, unlike the high-thermogenic brown adipocytes, the low-thermogenic brown adipocytes have ... a brown adipocyte subpopulation with low thermogenic activity coexisting with the classical high-thermogenic brown adipocytes ... the 2 brown adipocyte subpopulations underwent dynamic interconversions. Cold exposure converted low-thermogenic brown ...
... adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity. ... Signalling in the Initiation of UCP1 Gene Expression in HIB1B Brown Adipocytes. H. Y. Chen, Q. Liu, A. M. Salter, and M. A. ... Signalling in the Initiation of UCP1 Gene Expression in HIB1B Brown Adipocytes," PPAR Research, vol. 2013, Article ID 476049, 8 ...
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 ...
The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix.. Barneda D1 ... The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix ... The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix ... The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix ...
... ... Differentiated HIB1B brown adipocytes treated with serotonin had reduced levels of the thermogenic markers uncoupling protein 1 ... In parallel, serotonin led to 3-6-fold reduction in the gene expression of brown adipocyte differentiation markers, that is, ... Non-differentiated HIB1B cells and differentiated HIB1B brown adipocytes were treated with serotonin and their metabolism and ...
Here 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 ... described an important role played by the TGF-beta/Smad3 signaling pathway in modulating the appearance of brown adipocytes in ... described an important role played by the TGF-beta/Smad3 signaling pathway in modulating the appearance of brown adipocytes in ...
Abscisic acid enhances glucose disposal and induces brown fat activity in adipocytes in vitro and in vivo.. [Laura Sturla, ... ABA stimulates glucose uptake by myocytes and pre-adipocytes in vitro and oral ABA improves glycemic control in rats and in ... Here we investigated the role of the ABA/LANCL2 system in the regulation of glucose uptake and metabolism in adipocytes. ... As compared with insulin, ABA treatment of adipocytes induced lower triglyceride accumulation, CO ...
A high-throughput, image-based screen to identify kinases involved in brown adipocyte development ... A high-throughput, image-based screen to identify kinases involved in brown adipocyte development ... A high-throughput, image-based screen to identify kinases involved in brown adipocyte development ... A high-throughput, image-based screen to identify kinases involved in brown adipocyte development ...
... 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 ... Whether hypoxia also occurs in brown adipose tissue depots in obesity has been little considered. However, a recent study has ... Whether hypoxia also occurs in brown adipose tissue depots in obesity has been little considered. However, a recent study has ...
To investigate the browning effect of r-irisin on adipocytes, we used both 3T3-L1-derived adipocytes and primary rat adipocytes ... Irisin stimulates adipocyte browning via p38/ERK pathways. Primary rat adipocytes and 3T3-L1-derived adipocytes were treated ... White adipocytes store energy (e.g., triglycerides), whereas brown adipocytes consume energy (5,6). Many studies have shown ... Browning effect of r-irisin on rat primary adipocytes. Primary rat adipocytes were treated with r-irisin at indicated ...
In 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 ...
To more precisely define the specific role of IRS-1 in adipocyte biology, we established brown adipocyte cell lines from wild- ... Essential Role of Insulin Receptor Substrate 1 in Differentiation of Brown Adipocytes. Mathias Fasshauer, Johannes Klein, ... Thus, IRS-1 appears to be an important mediator of brown adipocyte maturation. Furthermore, this signaling molecule appears to ... Essential Role of Insulin Receptor Substrate 1 in Differentiation of Brown Adipocytes ...
PubMedScopusNorepinephrine-induced Na+ influx in brown adipocytes is cyclic AMP-mediated. Personposter BETA Nånberg, Eewa Søk i ... Norepinephrine-induced Na+ influx in brown adipocytes is cyclic AMP-mediated. Connolly, Eamonn The Wenner-Gren Institute, ... a method is described for measuring Na+ influx into isolated brown adipocytes, using short (30 s) incubations with 22Na+, ... The possibility that this beta-mediated norepinephrine-stimulated Na+ influx plays an important physiological role in brown ...
... subcutaneous adipose tissues in terms of macromolecular content and investigate transdifferentiation between white and brown ... 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 ...
... in white adipocytes, while in brown adipocytes, these measures increased by 10-35% primarily at the high dose (Fig. 6C and D). ... while increasing these measures in brown adipocytes. Our data establish 3-HIB as a novel adipocyte-derived regulator of ... 4C), brown adipocytes showed considerably higher mRNA expression levels of key BCAA catabolic enzymes, with two- to fivefold ... 5A and B), decreased lipid accumulation by 25-40% in both white and brown adipocytes (Fig. 5C), concomitant with 45-50% reduced ...
Thus, loss of TAK1 in adipocytes reduces the total number of adipocytes, increases browning of white adipose tissue, and may be ... Mice with adipocyte-specific TAK1 deficiency have reduced adipocyte numbers and are resistant to obesity induced by a high-fat ... in adipocytes results in an increased rate of apoptotic adipocyte death and increased numbers of M2 macrophages in white ... In addition, adipocyte-specific TAK1-deficient mice under a high-fat diet showed increased energy expenditure, which was ...
  • The adipocyte-derived hormone leptin e.g. which regulates energy intake and appetite was reportedly found at elevated levels in the bloodstream of obese subjects and is positively correlated with BMI [ 6 ]. (biomedcentral.com)
  • ABA stimulates glucose uptake by myocytes and pre-adipocytes in vitro and oral ABA improves glycemic control in rats and in healthy subjects. (sigmaaldrich.com)
  • We have identified in vitro inductive conditions in which mesenchymal cells isolated from the embryonic chicken limb bud differentiate into avian brown adipocyte-like cells (ABALCs) with the morphological and many of the biochemical properties of terminally differentiated brown adipocytes. (biomedcentral.com)
  • Researchers have developed a number of in vitro cell culture models to elucidate the details of differential gene regulation, and this approach has been used to characterize adipocytes-cells that store energy in the form of fat-for close to two decades. (elifesciences.org)
  • CD34 being also expressed on endothelial cells, we measured CD31, another endothelial marker, and expressed the brown adipocyte progenitors, as the CD34/CD31 mRNA ratio. (ed.ac.uk)
  • It has been suggested that this "transdifferentiation" could be an inherent property of white adipocytes and may not be due to a distinct cell type with this predisposition [ 16 ]. (biomedcentral.com)
  • Bone marrow adipocytes support AML survival. (bloodjournal.org)
  • Here, we present a reliable and straightforward two-dimensional (2D) coculture system for studying the interaction between tumor cells and bone marrow adipocytes, which reveals a dual effect of melanoma cell-derived factors on the bone marrow adipocytes differentiation and also poses a classic method for the mechanistic study of bone metastasis. (jove.com)
  • Utilizing multiple mouse models capable of genetically labeling different cellular populations, as well as single-cell RNA sequencing and 3D tissue profiling, we discovered a brown adipocyte subpopulation with low thermogenic activity coexisting with the classical high-thermogenic brown adipocytes within the BAT. (jci.org)