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.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.Lipoproteins: Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.Lipoproteins, LDL: A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.Lipoproteins, VLDL: A class of lipoproteins of very light (0.93-1.006 g/ml) large size (30-80 nm) particles with a core composed mainly of TRIGLYCERIDES and a surface monolayer of PHOSPHOLIPIDS and CHOLESTEROL into which are imbedded the apolipoproteins B, E, and C. VLDL facilitates the transport of endogenously made triglycerides to extrahepatic tissues. As triglycerides and Apo C are removed, VLDL is converted to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LOW-DENSITY LIPOPROTEINS from which cholesterol is delivered to the extrahepatic tissues.Lipoproteins, HDL: A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases.Hyperlipoproteinemia Type I: An inherited condition due to a deficiency of either LIPOPROTEIN LIPASE or APOLIPOPROTEIN C-II (a lipase-activating protein). The lack of lipase activities results in inability to remove CHYLOMICRONS and TRIGLYCERIDES from the blood which has a creamy top layer after standing.TriglyceridesApolipoprotein C-II: A 9-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS. It contains a cofactor for LIPOPROTEIN LIPASE and activates several triacylglycerol lipases. The association of Apo C-II with plasma CHYLOMICRONS; VLDL, and HIGH-DENSITY LIPOPROTEINS is reversible and changes rapidly as a function of triglyceride metabolism. Clinically, Apo C-II deficiency is similar to lipoprotein lipase deficiency (HYPERLIPOPROTEINEMIA TYPE I) and is therefore called hyperlipoproteinemia type IB.Lipoprotein(a): A lipoprotein that resembles the LOW-DENSITY LIPOPROTEINS but with an extra protein moiety, APOPROTEIN (A) also known as APOLIPOPROTEIN (A), linked to APOLIPOPROTEIN B-100 on the LDL by one or two disulfide bonds. High plasma level of lipoprotein (a) is associated with increased risk of atherosclerotic cardiovascular disease.Chylomicrons: A class of lipoproteins that carry dietary CHOLESTEROL and TRIGLYCERIDES from the SMALL INTESTINE to the tissues. Their density (0.93-1.006 g/ml) is the same as that of VERY-LOW-DENSITY LIPOPROTEINS.Triolein: (Z)-9-Octadecenoic acid 1,2,3-propanetriyl ester.Heparin: A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.Apolipoproteins C: A group of apolipoproteins that can readily exchange among the various classes of lipoproteins (HDL; VLDL; CHYLOMICRONS). After lipolysis of TRIGLYCERIDES on VLDL and chylomicrons, Apo-C proteins are normally transferred to HDL. The subtypes can modulate remnant binding to receptors, LECITHIN CHOLESTEROL ACYLTRANSFERASE, or LIPOPROTEIN LIPASE.Apolipoproteins: Protein components on the surface of LIPOPROTEINS. They form a layer surrounding the hydrophobic lipid core. There are several classes of apolipoproteins with each playing a different role in lipid transport and LIPID METABOLISM. These proteins are synthesized mainly in the LIVER and the INTESTINES.Receptors, Lipoprotein: Cell surface proteins that bind lipoproteins with high affinity. Lipoprotein receptors in the liver and peripheral tissues mediate the regulation of plasma and cellular cholesterol metabolism and concentration. The receptors generally recognize the apolipoproteins of the lipoprotein complex, and binding is often a trigger for endocytosis.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.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.Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.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)Hypertriglyceridemia: A condition of elevated levels of TRIGLYCERIDES in the blood.Apolipoproteins B: Major structural proteins of triacylglycerol-rich LIPOPROTEINS. There are two forms, apolipoprotein B-100 and apolipoprotein B-48, both derived from a single gene. ApoB-100 expressed in the liver is found in low-density lipoproteins (LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL). ApoB-48 expressed in the intestine is found in CHYLOMICRONS. They are important in the biosynthesis, transport, and metabolism of triacylglycerol-rich lipoproteins. Plasma Apo-B levels are high in atherosclerotic patients but non-detectable in ABETALIPOPROTEINEMIA.Receptors, LDL: Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.Cholesterol, HDL: Cholesterol which is contained in or bound to high-density lipoproteins (HDL), including CHOLESTEROL ESTERS and free cholesterol.Lipoproteins, IDL: A mixture of very-low-density lipoproteins (VLDL), particularly the triglyceride-poor VLDL, with slow diffuse electrophoretic mobilities in the beta and alpha2 regions which are similar to that of beta-lipoproteins (LDL) or alpha-lipoproteins (HDL). They can be intermediate (remnant) lipoproteins in the de-lipidation process, or remnants of mutant CHYLOMICRONS and VERY-LOW-DENSITY LIPOPROTEINS which cannot be metabolized completely as seen in FAMILIAL DYSBETALIPOPROTEINEMIA.Lipoprotein Lipase Activators: Compounds that increase the enzymatic activity of LIPOPROTEIN LIPASE. Lipoprotein lipase activators have a potential role in the treatment of OBESITY by increasing LIPID METABOLISM. Note that substances that increase the synthesis of lipoprotein lipase are not included here.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Apolipoproteins E: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Lipoproteins, HDL2: Low-density subclass of the high-density lipoproteins, with particle sizes between 8 to 13 nm.Lipoproteins, HDL3: Intermediate-density subclass of the high-density lipoproteins, with particle sizes between 7 to 8 nm. As the larger lighter HDL2 lipoprotein, HDL3 lipoprotein is lipid-rich.Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.Hyperlipoproteinemias: Conditions with abnormally elevated levels of LIPOPROTEINS in the blood. They may be inherited, acquired, primary, or secondary. Hyperlipoproteinemias are classified according to the pattern of lipoproteins on electrophoresis or ultracentrifugation.Sterol Esterase: An enzyme that catalyzes the hydrolysis of CHOLESTEROL ESTERS and some other sterol esters, to liberate cholesterol plus a fatty acid anion.Angiopoietins: A family of structurally-related angiogenic proteins of approximately 70 kDa in size. They have high specificity for members of the TIE RECEPTOR FAMILY.Low Density Lipoprotein Receptor-Related Protein-1: A LDL-receptor related protein involved in clearance of chylomicron remnants and of activated ALPHA-MACROGLOBULINS from plasma.Cholesterol, LDL: Cholesterol which is contained in or bound to low density lipoproteins (LDL), including CHOLESTEROL ESTERS and free cholesterol.Monoacylglycerol Lipases: An enzyme that catalyzes the hydrolysis of glycerol monoesters of long-chain fatty acids EC 3.1.1.23.Hyperlipidemias: Conditions with excess LIPIDS in the blood.Apolipoprotein C-III: A 9-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS and CHYLOMICRON REMNANTS. Apo C-III, synthesized in the liver, is an inhibitor of LIPOPROTEIN LIPASE. Apo C-III modulates the binding of chylomicron remnants and VLDL to receptors (RECEPTORS, LDL) thus decreases the uptake of triglyceride-rich particles by the liver cells and subsequent degradation. The normal Apo C-III is glycosylated. There are several polymorphic forms with varying amounts of SIALIC ACID (Apo C-III-0, Apo C-III-1, and Apo C-III-2).Apolipoproteins A: Structural proteins of the alpha-lipoproteins (HIGH DENSITY LIPOPROTEINS), including APOLIPOPROTEIN A-I and APOLIPOPROTEIN A-II. They can modulate the activity of LECITHIN CHOLESTEROL ACYLTRANSFERASE. These apolipoproteins are low in atherosclerotic patients. They are either absent or present in extremely low plasma concentration in TANGIER DISEASE.Milk: The white liquid secreted by the mammary glands. It contains proteins, sugar, lipids, vitamins, and minerals.Fatty Acids, Nonesterified: FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form.Cholesterol, VLDL: Cholesterol which is contained in or bound to very low density lipoproteins (VLDL). High circulating levels of VLDL cholesterol are found in HYPERLIPOPROTEINEMIA TYPE IIB. The cholesterol on the VLDL is eventually delivered by LOW-DENSITY LIPOPROTEINS to the tissues after the catabolism of VLDL to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LDL.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.Apolipoprotein B-100: A 513-kDa protein synthesized in the LIVER. It serves as the major structural protein of low-density lipoproteins (LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL). It is the ligand for the LDL receptor (RECEPTORS, LDL) that promotes cellular binding and internalization of LDL particles.Heparin Lyase: An enzyme of the isomerase class that catalyzes the eliminative cleavage of polysaccharides containing 1,4-linked D-glucuronate or L-iduronate residues and 1,4-alpha-linked 2-sulfoamino-2-deoxy-6-sulfo-D-glucose residues to give oligosaccharides with terminal 4-deoxy-alpha-D-gluc-4-enuronosyl groups at their non-reducing ends. (From Enzyme Nomenclature, 1992) EC 4.2.2.7.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)Kinetics: The rate dynamics in chemical or physical systems.Fasting: Abstaining from all food.Arteriosclerosis: Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries.Hyperlipoproteinemia Type IV: A hypertriglyceridemia disorder, often with autosomal dominant inheritance. It is characterized by the persistent elevations of plasma TRIGLYCERIDES, endogenously synthesized and contained predominantly in VERY-LOW-DENSITY LIPOPROTEINS (pre-beta lipoproteins). In contrast, the plasma CHOLESTEROL and PHOSPHOLIPIDS usually remain within normal limits.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.Emulsions: Colloids formed by the combination of two immiscible liquids such as oil and water. Lipid-in-water emulsions are usually liquid, like milk or lotion. Water-in-lipid emulsions tend to be creams. The formation of emulsions may be aided by amphiphatic molecules that surround one component of the system to form MICELLES.Hyperlipidemia, Familial Combined: A type of familial lipid metabolism disorder characterized by a variable pattern of elevated plasma CHOLESTEROL and/or TRIGLYCERIDES. Multiple genes on different chromosomes may be involved, such as the major late transcription factor (UPSTREAM STIMULATORY FACTORS) on CHROMOSOME 1.Apolipoprotein A-II: The second most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. It has a high lipid affinity and is known to displace APOLIPOPROTEIN A-I from HDL particles and generates a stable HDL complex. ApoA-II can modulate the activation of LECITHIN CHOLESTEROL ACYLTRANSFERASE in the presence of APOLIPOPROTEIN A-I, thus affecting HDL metabolism.Fat Emulsions, Intravenous: Emulsions of fats or lipids used primarily in parenteral feeding.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.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.Apolipoprotein B-48: A 241-kDa protein synthesized only in the INTESTINES. It serves as a structural protein of CHYLOMICRONS. Its exclusive association with chylomicron particles provides an indicator of intestinally derived lipoproteins in circulation. Apo B-48 is a shortened form of apo B-100 and lacks the LDL-receptor region.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Cholesterol Ester Transfer Proteins: Proteins that bind to and transfer CHOLESTEROL ESTERS between LIPOPROTEINS such as LOW-DENSITY LIPOPROTEINS and HIGH-DENSITY LIPOPROTEINS.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Colipases: Colipase I and II, consisting of 94-95 and 84-85 amino acid residues, respectively, have been isolated from porcine pancreas. Their role is to prevent the inhibitory effect of bile salts on the lipase-catalyzed intraduodenal hydrolysis of dietary long-chain triglycerides.Ultracentrifugation: Centrifugation with a centrifuge that develops centrifugal fields of more than 100,000 times gravity. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)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).Hypercholesterolemia: A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.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.Hyperlipoproteinemia Type III: An autosomal recessively inherited disorder characterized by the accumulation of intermediate-density lipoprotein (IDL or broad-beta-lipoprotein). IDL has a CHOLESTEROL to TRIGLYCERIDES ratio greater than that of VERY-LOW-DENSITY LIPOPROTEINS. This disorder is due to mutation of APOLIPOPROTEINS E, a receptor-binding component of VLDL and CHYLOMICRONS, resulting in their reduced clearance and high plasma levels of both cholesterol and triglycerides.Phosphatidylcholine-Sterol O-Acyltransferase: An enzyme secreted from the liver into the plasma of many mammalian species. It catalyzes the esterification of the hydroxyl group of lipoprotein cholesterol by the transfer of a fatty acid from the C-2 position of lecithin. In familial lecithin:cholesterol acyltransferase deficiency disease, the absence of the enzyme results in an excess of unesterified cholesterol in plasma. EC 2.3.1.43.Cholesterol, Dietary: Cholesterol present in food, especially in animal products.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Hyperlipoproteinemia Type V: A severe type of hyperlipidemia, sometimes familial, that is characterized by the elevation of both plasma CHYLOMICRONS and TRIGLYCERIDES contained in VERY-LOW-DENSITY LIPOPROTEINS. Type V hyperlipoproteinemia is often associated with DIABETES MELLITUS and is not caused by reduced LIPOPROTEIN LIPASE activity as in HYPERLIPOPROTEINEMIA TYPE I .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.Lymph: The interstitial fluid that is in the LYMPHATIC SYSTEM.Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes.Polysaccharide-Lyases: A group of carbon-oxygen lyases. These enzymes catalyze the breakage of a carbon-oxygen bond in polysaccharides leading to an unsaturated product and the elimination of an alcohol. EC 4.2.2.Hyperlipoproteinemia Type II: A group of familial disorders characterized by elevated circulating cholesterol contained in either LOW-DENSITY LIPOPROTEINS alone or also in VERY-LOW-DENSITY LIPOPROTEINS (pre-beta lipoproteins).Hypolipidemic Agents: Substances that lower the levels of certain LIPIDS in the BLOOD. They are used to treat HYPERLIPIDEMIAS.Postprandial Period: The time frame after a meal or FOOD INTAKE.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Apolipoprotein E2: One of three major isoforms of apolipoprotein E. In humans, Apo E2 differs from APOLIPOPROTEIN E3 at one residue 158 where arginine is replaced by cysteine (R158--C). In contrast to Apo E3, Apo E2 displays extremely low binding affinity for LDL receptors (RECEPTORS, LDL) which mediate the internalization and catabolism of lipoprotein particles in liver cells. ApoE2 allelic homozygosity is associated with HYPERLIPOPROTEINEMIA TYPE III.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.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)Particle Size: Relating to the size of solids.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Glycerides: GLYCEROL esterified with FATTY ACIDS.Oleic Acids: A group of fatty acids that contain 18 carbon atoms and a double bond at the omega 9 carbon.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)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.LDL-Receptor Related Protein-Associated Protein: A membrane protein found in the rough endoplasm reticulum (ENDOPLASMIC RETICULUM, ROUGH) that binds to LDL-RECEPTOR RELATED PROTEINS. It may function to prevent ligand binding of receptors during protein processing events within endosomal compartments.Pancreas: A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.Deoxyribonuclease HindIII: One of the Type II site-specific deoxyribonucleases (EC 3.1.21.4). It recognizes and cleaves the sequence A/AGCTT at the slash. HindIII is from Haemophilus influenzae R(d). Numerous isoschizomers have been identified. EC 3.1.21.-.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells.Homozygote: An individual in which both alleles at a given locus are identical.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Cell Line: Established cell cultures that have the potential to propagate indefinitely.Atherosclerosis: A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.Heparan Sulfate Proteoglycans: Ubiquitous macromolecules associated with the cell surface and extracellular matrix of a wide range of cells of vertebrate and invertebrate tissues. They are essential cofactors in cell-matrix adhesion processes, in cell-cell recognition systems, and in receptor-growth factor interactions. (From Cancer Metastasis Rev 1996; 15(2): 177-86; Hepatology 1996; 24(3): 524-32)Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Carboxylic Ester Hydrolases: Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.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.Blood Glucose: Glucose in blood.Apoproteins: The protein components of a number of complexes, such as enzymes (APOENZYMES), ferritin (APOFERRITINS), or lipoproteins (APOLIPOPROTEINS).Chromatography, Agarose: A method of gel filtration chromatography using agarose, the non-ionic component of agar, for the separation of compounds with molecular weights up to several million.alpha-Macroglobulins: Glycoproteins with a molecular weight of approximately 620,000 to 680,000. Precipitation by electrophoresis is in the alpha region. They include alpha 1-macroglobulins and alpha 2-macroglobulins. These proteins exhibit trypsin-, chymotrypsin-, thrombin-, and plasmin-binding activity and function as hormonal transporters.Scavenger Receptors, Class B: A family of scavenger receptors that are predominately localized to CAVEOLAE of the PLASMA MEMBRANE and bind HIGH DENSITY LIPOPROTEINS.Hypolipoproteinemias: Conditions with abnormally low levels of LIPOPROTEINS in the blood. This may involve any of the lipoprotein subclasses, including ALPHA-LIPOPROTEINS (high-density lipoproteins); BETA-LIPOPROTEINS (low-density lipoproteins); and PREBETA-LIPOPROTEINS (very-low-density lipoproteins).Plant Oils: Oils derived from plants or plant products.Protamines: A group of simple proteins that yield basic amino acids on hydrolysis and that occur combined with nucleic acid in the sperm of fish. Protamines contain very few kinds of amino acids. Protamine sulfate combines with heparin to form a stable inactive complex; it is used to neutralize the anticoagulant action of heparin in the treatment of heparin overdose. (From Merck Index, 11th ed; Martindale, The Extra Pharmacopoeia, 30th ed, p692)Heparitin Sulfate: A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Antigens, CD36: Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.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.Molecular Weight: The sum of the weight of all the atoms in a molecule.Apolipoprotein C-I: A 6.6-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS; INTERMEDIATE-DENSITY LIPOPROTEINS; and HIGH-DENSITY LIPOPROTEINS. Apo C-I displaces APO E from lipoproteins, modulate their binding to receptors (RECEPTORS, LDL), and thereby decrease their clearance from plasma. Elevated Apo C-I levels are associated with HYPERLIPOPROTEINEMIA and ATHEROSCLEROSIS.EsterasesSodium Chloride: A ubiquitous sodium salt that is commonly used to season food.Mice, Inbred C57BLRabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.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).IndolizinesGlycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.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.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Aorta: The main trunk of the systemic arteries.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Apolipoprotein E3: A 34-kDa glycosylated protein. A major and most common isoform of apolipoprotein E. Therefore, it is also known as apolipoprotein E (ApoE). In human, Apo E3 is a 299-amino acid protein with a cysteine at the 112 and an arginine at the 158 position. It is involved with the transport of TRIGLYCERIDES; PHOSPHOLIPIDS; CHOLESTEROL; and CHOLESTERYL ESTERS in and out of the cells.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.Receptors, Scavenger: A large group of structurally diverse cell surface receptors that mediate endocytic uptake of modified LIPOPROTEINS. Scavenger receptors are expressed by MYELOID CELLS and some ENDOTHELIAL CELLS, and were originally characterized based on their ability to bind acetylated LOW-DENSITY LIPOPROTEINS. They can also bind a variety of other polyanionic ligand. Certain scavenger receptors can internalize micro-organisms as well as apoptotic cells.SepharoseMice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Diet, Atherogenic: A diet that contributes to the development and acceleration of ATHEROGENESIS.Rhizopus: A genus of zygomycetous fungi of the family Mucoraceae, order MUCORALES, a common saprophyte and facultative parasite of mature fruits and vegetables. It may cause cerebral mycoses in diabetes and cutaneous infection in severely burned patients.Phosphatidylcholines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a choline moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and choline and 2 moles of fatty acids.Apoprotein(a): A large and highly glycosylated protein constituent of LIPOPROTEIN (A). It has very little affinity for lipids but forms disulfide-linkage to APOLIPOPROTEIN B-100. Apoprotein(a) has SERINE PROTEINASE activity and can be of varying sizes from 400- to 800-kDa. It is homologous to PLASMINOGEN and is known to modulate THROMBOSIS and FIBRINOLYSIS.Dyslipidemias: Abnormalities in the serum levels of LIPIDS, including overproduction or deficiency. Abnormal serum lipid profiles may include high total CHOLESTEROL, high TRIGLYCERIDES, low HIGH DENSITY LIPOPROTEIN CHOLESTEROL, and elevated LOW DENSITY LIPOPROTEIN CHOLESTEROL.Lactones: Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.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.Sulfur Oxides: Inorganic oxides of sulfur.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Phospholipid Transfer Proteins: A ubiquitous family of proteins that transport PHOSPHOLIPIDS such as PHOSPHATIDYLINOSITOL and PHOSPHATIDYLCHOLINE between membranes. They play an important role in phospholipid metabolism during vesicular transport and SIGNAL TRANSDUCTION.Coronary Disease: An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels.LDL-Receptor Related Proteins: A family of proteins that share sequence similarity with the low density lipoprotein receptor (RECEPTORS, LDL).Sterol O-Acyltransferase: An enzyme that catalyzes the formation of cholesterol esters by the direct transfer of the fatty acid group from a fatty acyl CoA derivative. This enzyme has been found in the adrenal gland, gonads, liver, intestinal mucosa, and aorta of many mammalian species. EC 2.3.1.26.Food: Any substances taken in by the body that provide nourishment.Lipid Metabolism, Inborn Errors: Errors in the metabolism of LIPIDS resulting from inborn genetic MUTATIONS that are heritable.Geotrichum: A mitosporic Saccharomycetales fungal genus, various species of which have been isolated from pulmonary lesions. Teleomorphs include Dipodascus and Galactomyces.Starvation: Lengthy and continuous deprivation of food. (Stedman, 25th ed)Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.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.Hydroxymethylglutaryl CoA Reductases: Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.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.Electrophoresis, Agar Gel: Electrophoresis in which agar or agarose gel is used as the diffusion medium.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.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.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.Eating: The consumption of edible substances.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.
Caloric restriction leads to regional specialisation of adipocyte function in the rat. (1/1971)
The study analysed the responses of three metabolic parameters in five distinct adipose tissue depots to caloric restriction (4 weeks) in the rat. The aims were to evaluate whether specific adipose tissue depots were recruited for triacylglycerol (TAG) storage and/or mobilisation, and to determine to what extent specific adipose tissue depots exhibited preferences for the source of fatty acid (FA) for TAG storage. Caloric restriction led to a general enhancement of the response of lipoprotein lipase (LPL), FA synthesis and glucose utilisation to a meal. Effects were particularly marked in the parametrial, perirenal and interscapular depots compared with mesenteric and subcutaneous depots. There was no evidence that individual depots selectively expressed a preference for the pathways concerned with the generation of FA for storage (the exogenous (LPL) and the endogenous (synthesis) pathway). However, the temporal sequence of activation of these pathways differed in a manner consistent with a switch from preponderant use of FA produced via de novo synthesis during the very early phase of feeding towards later use of FA derived from circulating TAG. The overall excursions in insulin levels observed in the calorie-restricted rats were comparable to those found in free-feeding rats, but the magnitude and the rapidity of the individual metabolic responses of the adipocyte were augmented. The data are consistent with a general enhancement of insulin sensitivity and responsiveness in adipose tissue of calorie-restricted rats, together with adaptive regional specialisation of adipocyte function. These adaptations would be predicted to facilitate the immediate conservation of dietary nutrients by promoting their storage as the FA or glycerol moieties of adipose tissue TAG and thereby to ensure the regulated release of FA and glycerol from adipose tissue in accordance with the requirement for glucose conservation and/or production. (+info)Binding of beta-VLDL to heparan sulfate proteoglycans requires lipoprotein lipase, whereas ApoE only modulates binding affinity. (2/1971)
The binding of beta-VLDL to heparan sulfate proteoglycans (HSPG) has been reported to be stimulated by both apoE and lipoprotein lipase (LPL). In the present study we investigated the effect of the isoform and the amount of apoE per particle, as well as the role of LPL on the binding of beta-VLDL to HSPG. Therefore, we isolated beta-VLDL from transgenic mice, expressing either APOE*2(Arg158-->Cys) or APOE*3-Leiden (E2-VLDL and E3Leiden-VLDL, respectively), as well as from apoE-deficient mice containing no apoE at all (Enull-VLDL). In the absence of LPL, the binding affinity and maximal binding capacity of all beta-VLDL samples for HSPG-coated microtiter plates was very low. Addition of LPL to this cell-free system resulted in a 12- to 55-fold increase in the binding affinity and a 7- to 15-fold increase in the maximal binding capacity (Bmax). In the presence of LPL, the association constant (Ka) tended to increase in the order Enull-VLDLInduced mutant mouse lines that express lipoprotein lipase in cardiac muscle, but not in skeletal muscle and adipose tissue, have normal plasma triglyceride and high-density lipoprotein-cholesterol levels. (3/1971)
The tissue-specific expression of lipoprotein lipase (LPL) in adipose tissue (AT), skeletal muscle (SM), and cardiac muscle (CM) is rate-limiting for the uptake of triglyceride (TG)-derived free fatty acids and decisive in the regulation of energy balance and lipoprotein metabolism. To investigate the tissue-specific metabolic effects of LPL, three independent transgenic mouse lines were established that expressed a human LPL (hLPL) minigene predominantly in CM. Through cross-breeding with heterozygous LPL knockout mice, animals were generated that produced hLPL mRNA and enzyme activity in CM but lacked the enzyme in SM and AT because of the absence of the endogenous mouse LPL gene (L0-hLPL). LPL activity in CM and postheparin plasma of L0-hLPL mice was reduced by 34% and 60%, respectively, compared with control mice. This reduced LPL expression was sufficient to rescue LPL knockout mice from neonatal death. L0-hLPL animals developed normally with regard to body weight and body-mass composition. Plasma TG levels in L0-hLPL animals were increased up to 10-fold during the suckling period but normalized after weaning and decreased in adult animals. L0-hLPL mice had normal plasma high-density lipoprotein (HDL)-cholesterol levels, indicating that LPL expression in CM alone was sufficient to allow for normal HDL production. The absence of LPL in SM and AT did not cause detectable morphological or histopathological changes in these tissues. However, the lipid composition in AT and SM exhibited a marked decrease in polyunsaturated fatty acids. From this genetic model of LPL deficiency in SM and AT, it can be concluded that CM-specific LPL expression is a major determinant in the regulation of plasma TG and HDL-cholesterol levels. (+info)Response of adipose tissue lipoprotein lipase to the cephalic phase of insulin secretion. (4/1971)
Modulation of lipoprotein lipase (LPL) allows a tissue-specific partitioning of triglyceride-derived fatty acids, and insulin is a major modulator of its activity. The present studies were aimed to assess in rats the contribution of insulin to the response of adipose tissue and muscle LPL to food intake. Epididymal and retroperitoneal adipose LPL rose 65% above fasting values as early as 1 h after the onset of a 30-min high-carbohydrate meal, with a second activity peak 1 h later that was maintained for an additional 2 h. Soleus muscle LPL was decreased by 25% between 0.5 and 4 h after meal intake. The essential contribution of insulin to the LPL response to food intake was determined by preventing the full insulin response to meal intake by administration of diazoxide (150 mg/kg body wt, in the meal). The usual postprandial changes in adipose and muscle LPL did not occur in the absence of an increase in insulinemia. However, the early (60 min) increase in adipose tissue LPL was not prevented by the drug, likely because of the maintenance of the early centrally mediated phase of insulin secretion. In a subsequent study, rats chronically implanted with a gastric cannula were used to demonstrate that the postprandial rise in adipose LPL is independent of nutrient absorption and can be elicited by the cephalic (preabsorptive) phase of insulin secretion. Obese Zucker rats were used because of their strong cephalic insulin response. After an 8-h fast, rats were fed a liquid diet ad libitum (orally, cannula closed), sham fed (orally, cannula opened), or fed directly into the stomach via the cannula during 4 h. Insulinemia increased 10-fold over fasting levels in ad libitum- and intragastric-fed rats and threefold in sham-fed rats. Changes in adipose tissue LPL were proportional to the elevation in plasma insulin levels, demonstrating that the cephalic-mediated rise in insulinemia, in the absence of nutrient absorption, stimulates adipose LPL. These results demonstrate the central role of insulin in the postprandial response of tissue LPL, and they show that cephalically mediated insulin secretion is able to stimulate adipose LPL. (+info)Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase. (5/1971)
Lipoprotein lipase and the receptor-associated protein (RAP) bind to overlapping sites on the low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor (LRP). We have investigated if lipoprotein lipase interacts with the RAP binding but structurally distinct receptor sortilin/neurotensin receptor-3. We show, by chemical cross-linking and surface plasmon resonance analysis, that soluble sortilin binds lipoprotein lipase with an affinity similar to that of LRP. The binding was inhibited by heparin and RAP and by the newly discovered sortilin ligand neurotensin. In 35S-labeled 3T3-L1 adipocytes treated with the cross-linker dithiobis(succinimidyl propionate), lipoprotein lipase-containing complexes were isolated by anti-sortilin antibodies. To elucidate function in cells, sortilin-negative Chinese hamster ovary cells were transfected with full-length sortilin and shown to express about 8% of the receptors on the cell surface. These cells degraded 125I-labeled lipoprotein lipase much faster than the wild-type cells. The degradation was inhibited by unlabeled lipoprotein lipase, indicating a saturable pathway, and by RAP and heparin. Moreover, inhibition by the weak base chloroquine suggested that degradation occurs in an acidic vesicle compartment. The results demonstrate that sortilin is a multifunctional receptor that binds lipoprotein lipase and, when expressed on the cell surface, mediates its endocytosis and degradation. (+info)Role of protein kinase C in the translational regulation of lipoprotein lipase in adipocytes. (6/1971)
The hypertriglyceridemia of diabetes is accompanied by decreased lipoprotein lipase (LPL) activity in adipocytes. Although the mechanism for decreased LPL is not known, elevated glucose is known to increase diacylglycerol, which activates protein kinase C (PKC). To determine whether PKC is involved in the regulation of LPL, we studied the effect of 12-O-tetradecanoyl phorbol 13-acetate (TPA) on adipocytes. LPL activity was inhibited when TPA was added to cultures of 3T3-F442A and rat primary adipocytes. The inhibitory effect of TPA on LPL activity was observed after 6 h of treatment, and was observed at a concentration of 6 nM. 100 nM TPA yielded maximal (80%) inhibition of LPL. No stimulation of LPL occurred after short term addition of TPA to cultures. To determine whether TPA treatment of adipocytes decreased LPL synthesis, cells were labeled with [35S]methionine and LPL protein was immunoprecipitated. LPL synthetic rate decreased after 6 h of TPA treatment. Western blot analysis of cell lysates indicated a decrease in LPL mass after TPA treatment. Despite this decrease in LPL synthesis, there was no change in LPL mRNA in the TPA-treated cells. Long term treatment of cells with TPA is known to down-regulate PKC. To assess the involvement of the different PKC isoforms, Western blotting was performed. TPA treatment of 3T3-F442A adipocytes decreased PKC alpha, beta, delta, and epsilon isoforms, whereas PKC lambda, theta, zeta, micro, iota, and gamma remained unchanged or decreased minimally. To directly assess the effect of PKC inhibition, PKC inhibitors (calphostin C and staurosporine) were added to cultures. The PKC inhibitors inhibited LPL activity rapidly (within 60 min). Thus, activation of PKC did not increase LPL, but inhibition of PKC resulted in decreased LPL synthesis by inhibition of translation, indicating a constitutive role of PKC in LPL gene expression. (+info)Association of lipoprotein lipase gene polymorphisms with coronary artery disease. (7/1971)
OBJECTIVES: The purpose of this study was to test whether the HindIII (+) and PvuII (-) or (+) restriction enzyme-defined alleles are associated with angiographic coronary artery disease (CAD). BACKGROUND: Lipoprotein lipase (LPL) plays a central role in lipid metabolism, hydrolyzing triglyceride in chylomicrons and very low density lipoproteins. Polymorphic variants of the LPL gene are common and might affect risk of CAD. METHODS: Blood was drawn from 725 patients undergoing coronary angiography. Leukocyte deoxyribonucleic acid segments containing the genomic sites were amplified by the polymerase chain reaction and digested, and polymorphisms were identified after electrophoresis in 1.5% agarose gel. RESULTS: In no-CAD control subjects (n = 168), HindIII (-) and (+) allelic frequencies were 28.6% and 71.4%, and (-) and (+) alleles were carried by 44.0% and 86.9% of subjects, respectively. Control PvuII (-) and (+) allelic frequencies were 41.7% and 58.3%, and (-) and (+) alleles were carried by 64.3% and 81.0%, respectively. In CAD patients (>60% stenosis; n = 483), HindIII (+) allelic carriage was increased (93.8% of patients, odds ratio [OR] = 2.28, confidence interval [CI] 1.27 to 4.00). Also, PvuII (-) allelic carriage tended to be more frequent in CAD patients (OR = 1.33, CI 0.92 to 1.93). Adjusted for six CAD risk factors and the other polymorphism, HindIII (+) carriage was associated with an OR = 2.86, CI 1.50 to 5.42, p = 0.0014, and PvulI (-) carriage, OR = 1.42, CI 0.95 to 2.12, p = 0.09. The two polymorphisms were in strong linkage disequilibrium, and a haplotype association was suggested. CONCLUSIONS: The common LPL polymorphic allele, HindIII (+), is moderately associated with CAD, and the PvuII (-) allele is modestly associated (trend). Genetic variants of LPL deserve further evaluation as risk factors for CAD. (+info)Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins. (8/1971)
Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG-rich lipoproteins in the formation of HDL particles. As both these lipoproteins play an important role in the pathogenesis of atherosclerotic vascular disease, we sought to assess the relationship between post-heparin LPL (PH-LPL) activity and lipids and lipoproteins in a large, well-defined cohort of Dutch males with coronary artery disease (CAD). These subjects were drawn from the REGRESS study, totaled 730 in number and were evaluated against 75 healthy, normolipidemic male controls. Fasting mean PH-LPL activity in the CAD subjects was 108 46 mU/ml, compared to 138 44 mU/ml in controls (P < 0.0001). When these patients were divided into activity quartiles, those in the lowest versus the highest quartile had higher levels of TG (P < 0.001), VLDLc and VLDL-TG (P = 0.001). Conversely, levels of TC, LDL, and HDLc were lower in these patients (P = 0.001, P = 0.02, and P = 0.001, respectively). Also, in this cohort PH-LPL relationships with lipids and lipoproteins were not altered by apoE genotypes. The frequency of common mutations in the LPL gene associated with partial LPL deficiency (N291S and D9N carriers) in the lowest quartile for LPL activity was more than double the frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contrast, the frequency of the S447X LPL variant rose from 11.5% in the lowest to 18.3% (P = 0.006) in the highest quartile. This study, in a large cohort of CAD patients, has shown that PH-LPL activity is decreased (22%; P = 0.001) when compared to controls; that the D9N and N291S, and S447X LPL variants are genetic determinants, respectively, in CAD patients of low and high LPL PH-LPL activities; and that PH-LPL activity is strongly associated with changes in lipids and lipoproteins. (+info)
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TriglyceridesDeficiencyGeneLipidsHepaticInsulinProteinVLDLPostheparin plasmaChylomicronsFatty acidsEndothelial cellsActivityMiceGlycosylphosphatidylinositolPlasmaAdipose tissue lipoprotein lipase activityCholesterolMutationsParticlesAntibodyProcessing of triglyceride-rich lipoproteinsRegulationUptakeGeneticSkeletalPancreatic lipaseHumansActivity Assay KitHydrolysis of TG-rich lipoproteinsAtherosclerosisHyperlipoproteinemiaCardiovascular diseaseCatabolismMediatesTriglyceride lipase activitiesRegulatesMonoclonal
Triglycerides5
- Lipoprotein lipase then provides essential assistance for the transfer of triglycerides from the lipoproteins in your blood to your fatty tissues, heart and muscles. (sfgate.com)
- Lipoprotein lipase is an enzyme that is important for the transfer of triglycerides from your blood lipoproteins into your tissues. (sfgate.com)
- Lipoprotein lipase breaks down the triglycerides in the lipoproteins to smaller fatty acids and monoglycerides that are transported into your tissues and either burned for fuel or re-assembled into triglycerides for storage. (sfgate.com)
- January 7th, 2010 - Lipoprotein lipase (LPL) is an enzyme that breaks apart fat (triglycerides) into their fatty acid components for transport and use inside cells. (wordpress.com)
- Lipoprotein lipase is the principal enzyme that hydrolyzes circulating triglycerides and liberates free fatty acids that can be used as energy by cardiac muscle. (jci.org)
Deficiency3
- Also searched for Hyperlipoproteinemia Type I , Lipoprotein lipase deficiency , and Familial Chylomicronemias . (clinicaltrials.gov)
- DAG oil was evaluated in healthy cats and in a feline model of hypertriglyceridemia as a result of lipoprotein lipase (LPL) deficiency. (umsystem.edu)
- Objective - To assess effects of deficiency of lipoprotein lipase (LPL) on body condition scores and lean and fat body masses of adult cats. (elsevier.com)
Gene1
- An Asn291Ser mutation in exon 6 of the lipoprotein lipase gene (LPL) frequently occurs in Caucasians (2-4%) and results in a partial catalytic defect. (elsevier.com)
Lipids1
- The objectives of this investigation were to establish appropriate working conditions for the postheparin plasma lipoprotein lipase (LPL) assay and to study relationships between fat deposition and plasma lipids, very low density lipoprotein (VLDL) lipids, VLDL-subfractions and postheparin plasma LPL activity in growing pigs. (ajas.info)
Hepatic1
- Postheparin plasma preincubated with SDS (20-50 mM) at 26 C for 45 minutes inhibited hepatic lipase activity. (ajas.info)
Insulin5
- Insulin and lipoprotein lipase work together in your body to use extra calories from carbohydrates in your diet to make and store fats. (sfgate.com)
- Insulin stimulates lipoprotein lipase production, especially in your fatty tissues. (sfgate.com)
- http://healthyeating.sfgate.com/lipoprotein-lipase-insulin-6065.html. (sfgate.com)
- Lipoprotein Lipase & Insulin" last modified December 27, 2018. (sfgate.com)
- 1. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men. (wordpress.com)
Protein1
VLDL2
- The fats made in your liver from extra carbohydrates in your diet are packaged into blood transporters called very low-density lipoproteins, or VLDL, which are shipped into your blood. (sfgate.com)
- Lipoprotein lipase can bind with your blood lipoproteins, including VLDL from your liver and chylomicrons from your small intestine, after a meal. (sfgate.com)
Postheparin plasma1
- Hearts, but not postheparin plasma, of these mice contained human lipoprotein lipase activity. (jci.org)
Chylomicrons1
- Lipoprotein lipase is a digestive enzyme that helps the body break down structures called chylomicrons. (gonerd.me)
Fatty acids1
- An increase in lipoprotein lipase activity means an increase in the flow of fatty acids into the cell. (wordpress.com)
Endothelial cells1
- Although lipoprotein lipase is expressed by and is found on the surface of cardiomyocytes, its transfer to the luminal surface of endothelial cells is thought to be required for lipoprotein lipase actions. (jci.org)
Activity3
- Skeletal muscle lipoprotein lipase activity in CON, EX-DEF and EX-BAL. (biomedcentral.com)
- Lipoprotein lipase activity in the fat cells of the abdominal region is greater in men than in women, and reduced testosterone levels only increases activity. (wordpress.com)
- The Increase Activity of Lipoprotein Lipase (LPL) Enzyme and Histophatological Changes of Liver of Hypercholesterolemic Rat (Rattus norvegicus) Induced by Ethanolic Extract of Ant Plant (Myrmecodia sp. (crossref.org)
Mice1
- Adenovirus-mediated rescue of lipoprotein lipase-deficient mice. (elsevier.com)
Glycosylphosphatidylinositol1
- To study whether nontransferable lipoprotein lipase has physiological actions, we placed an α-myosin heavy-chain promoter upstream of a human lipoprotein lipase minigene construct with a glycosylphosphatidylinositol anchoring sequence on the carboxyl terminal region. (jci.org)
Plasma2
- Selective measurement of two lipase activities in post heparin plasma from normal subjects and patients with hyperlipoproteinemia. (nii.ac.jp)
- Rat Lpl ELISA Kit is a Sandwich ELISA KIT detecting the concentration of Lipoprotein lipase in Rat serum, plasma, tissue homogenates and other biological fluids. (lifescience-market.com)
Adipose tissue lipoprotein lipase activity4
- 1. Alloxan-diabetic rats showed raised plasma triglyceride levels and low adipose tissue lipoprotein lipase activity compared with controls. (clinsci.org)
- Obese subjects have elevated adipose tissue lipoprotein lipase activity per fat cell when compared with lean control subjects. (natrilha.info)
- 0.05) was obtained between the adipose tissue lipoprotein lipase activity and the level of physical activity. (bisp-surf.de)
- Our data suggest that even moderate inter-group differences in the physical training activity are reflected as measureable alterations in the adipose tissue lipoprotein lipase activity in man. (bisp-surf.de)
Cholesterol18
- It is also involved in promoting the cellular uptake of chylomicron remnants, cholesterol-rich lipoproteins, and free fatty acids. (wikipedia.org)
- it has a higher affinity for large triacylglyceride-rich lipoproteins than cholesterol-rich lipoproteins. (wikipedia.org)
- These mutations occur at high frequencies in the general population (up to 5%) and are associated with elevated TGs, decreased high-density lipoprotein (HDL) cholesterol levels, and concomitantly with a higher incidence of cardiovascular disease (CVD), 6-13 compared with noncarriers. (ahajournals.org)
- In the CAD group, those with the Msp M1 allele had higher levels of total cholesterol (TC) (p = 0026) and low-density lipoprotein cholesterol (LDL-C) than those with the Msp M2 allele. (wiley.com)
- In the control group, CETP, the Msp M2 allele was associated with a higher level of high-density lipoprotein cholesterol (HDL-C) (p = 0.012) than the Msp M1 allele. (wiley.com)
- I had Fasting test Cholesterol 158/triglyceride 45/ HDL 77 / LDL calculated 72 \cholesterol high density lipoprotein 2.1 /cholesterol nonHDL81 Normal? (healthtap.com)
- This was associated with a marked down-regulation of cholesterol 7α-hydroxylase in the liver and a severe reduction of lipoprotein lipase abundance in skeletal muscle and adipose tissue. (aspetjournals.org)
- The former abnormality can contribute to hypercholesterolemia by limiting cholesterol catabolism, whereas the latter may contribute to hypertriglyceridemia and VLDL accumulation by limiting triglyceride-rich lipoprotein clearance in CsA-treated animals. (aspetjournals.org)
- The plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, and phospholipids in the HL/EL-dko mice were markedly higher than those in the single-knockout mice. (ahajournals.org)
- HDL from all 3 lipase knockout models had an increased cholesterol efflux capacity but reduced clearance of HDL cholesteryl esters versus control mice. (ahajournals.org)
- lipoprotein - n. one of a group of compounds, found in blood plasma and lymph, each consisting of a protein (see apolipoprotein) combined with a lipid (which may be cholesterol, a triglyceride, or a phospholipid). (enacademic.com)
- Lipase is absolutely key to proper fat digestion, which affects so many bodily functions as well as health st Heart Rate Zone For Fat Burn - Weight Loss Clinic Opelousas La Best Heart Rate Zone For Fat Burn Hdl High Density Lipoprotein Cholesterol Weight Loss Management In Flint Mi. (natrilha.info)
- A review of low- density lipoprotein cholesterol its impact on cardiovascular disease morbidity , treatment strategies mortality. (natrilha.info)
- The study has broad- ranging implications relative to increased free radical damage , although carried out on pigs loss of mitochondria productionThis is a st Heart Rate Zone For Fat Burn - Weight Loss Clinic Opelousas La Best Heart Rate Zone For Fat Burn Hdl High Density Lipoprotein Cholesterol Weight Loss Management In. (natrilha.info)
- Body fat decreases in total low- density lipoprotein cholesterol were greater in women whose adipose tissue LPL activity decreased with weight loss. (natrilha.info)
- This process influences the production of high-density lipoprotein (HDL), which takes up tissue cholesterol for transport to the liver for excretion. (edu.au)
- To help clarify this issue, we investigated 144 outwardly healthy male Mediterranean migrants (from Italy and Greece), age between 40 and 70 years and resident in Australia, for associations between two common LPL restriction site polymorphisms and the following lipid and lipoprotein phenotypes: total plasma cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triacylglycerides. (edu.au)
- T) and cholesteryl ester transfer protein (CETP I405V) genes affect high-density lipoprotein cholesterol (HDL-c) levels, but their relationship with cardiovascular disease and their combined effect is unclear. (cdc.gov)
Mutations3
- In this instance besides LPL also other loss-of-function mutations in genes that regulate catabolism of triglyceride-rich lipoproteins (like e.g. (wikipedia.org)
- LPL promoter mutations are not rare and may contribute to the lipoprotein phenotype of FCH, at least in the subset of patients who show reduced postheparin plasma LPL activity. (renalandurologynews.com)
- T polymorphism can not explain the observed linkage of lipoprotein size phenotypes to the LIPC region and, therefore, that there are one or more additional functional mutations in or near LIPC influencing HDL, and potentially LDL, size variation. (ahajournals.org)
Particles7
- tg rich lipoprotein particles. (healthtap.com)
- A major portion of available fatty acids for adipocyte uptake is derived from lipoprotein lipase (LPL)-mediated hydrolysis of circulating lipoprotein particles. (biomedcentral.com)
- Mediates margination of triglyceride-rich lipoprotein particles in capillaries (PubMed:24726386). (sdsc.edu)
- Associates with lipoprotein particles in blood plasma (PubMed:11342582, PubMed:11893776). (sdsc.edu)
- Despite this, intermediate density particles accumulated to a level 2.4-times normal because their subsequent conversion to low density lipoprotein has been almost totally inhibited. (ox.ac.uk)
- Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules around the body within the water outside cells. (natrilha.info)
- Adipose tissue lipoprotein lipase (LPL) hydrolyzes triglyceride from these lipoprotein particles to facilitate their entry into adipocytes for storage. (elsevier.com)
Antibody3
- Lipoprotein Lipase/LPL Monoclonal antibody specifically detects Lipoprotein Lipase/LPL in Human samples. (fishersci.com)
- There are currently no images for Lipoprotein Lipase/LPL Antibody Pair (H00004023-PW1). (novusbio.com)
- Western blot analysis of Lipoprotein lipase on human placenta tissue lysate using anti-Lipoprotein lipase antibody at 1/1,000 dilution. (huabio.com)
Processing of triglyceride-rich lipoproteins1
- Lipoprotein lipase (LPL) is responsible for the intravascular processing of triglyceride-rich lipoproteins. (pnas.org)
Regulation1
- This investigation considers the regulation of LPL by lipoproteins and LVPs, and their roles in the LPL-mediated anti-HCV function. (bmj.com)
Uptake6
- LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. (wikipedia.org)
- Thus, lipoprotein lipase expressed on the surface of cardiomyocytes can increase lipid uptake and produce cardiomyopathy. (jci.org)
- Lipoprotein lipase (LPL), the primary enzyme responsible for tissue uptake of triglyceride fatty acids, may strongly influence both maternal milk fat secretion and pup blubber deposition. (springer.com)
- Lipoprotein lipase (LPL) serves as a central factor in hydrolysis of triacylglycerol and uptake of free fatty acids from the plasma. (mdpi.com)
- The objective of this study was to determine whether fatty acid composition of adipose tissue from LPL-deficient subjects reflects maintenance of lipid stores through increased lipogenesis or through alternate mechanisms of lipoprotein uptake. (elsevier.com)
- In this renewal we propose to study the pathways required for uptake of both FFAs and lipoprotein-derived fatty acids by altering expression of both LpL and CD36. (grantome.com)
Genetic1
- 5. We conclude that genetic variants at the lipoprotein lipase locus occur commonly in subjects with this syndrome (four out of 18 subjects with probably functional mutants) and may affect the individual's response to obesity and diabetes mellitus for the development of lipaemia. (clinsci.org)
Skeletal4
- Unusual metabolic characteristics in skeletal muscles of transgenic rabbits for human lipoprotein lipase. (biomedsearch.com)
- Skeletal muscle lipoprotein lipase activity in CON, EX-DEF and EX-BAL. (biomedcentral.com)
- Lipoprotein-lipase activity of human skeletal muscle and adipose tissue after intensive physical exercise by: Lithell, Hans, et al. (bisp-surf.de)
- Some factors determining the lipoprotein-lipase activity of skeletal muscle during heavy exercise by: Lithell, Hans, et al. (bisp-surf.de)
Pancreatic lipase1
- Yes research has suggested that fluorinated water may be responsible for the decreased activity of both pancreatic lipase protease. (natrilha.info)
Humans3
- Little is known about the fate of the lipolytic products produced by the action of lipoprotein lipase (LPL) on circulating triglyceride-rich lipoproteins in humans. (elsevier.com)
- These results indicate that there is escape, or spillover, of the lipolytic products of LPL action on triglyceride-rich lipoproteins in humans. (elsevier.com)
- Zheng, C.et al : Lipoprotein lipase bound to apoB lipoproteins accelerates clearance of postprandial lipoproteins in humans. (immuquest.com)
Activity Assay Kit1
- The Lipoprotein Lipase ( LPL ) Activity Assay Kit is a simple, fluorometric assay that quantitatively measures LPL activity in plasma, serum, and lysates in a 96-well microtiter plate format. (cellbiolabs.com)
Hydrolysis of TG-rich lipoproteins1
- Major functions of LPL include the hydrolysis of TG-rich lipoproteins and release of non-esterified fatty acid (NEFA), which are taken up and used for metabolic energy in peripheral tissue such as muscle, or are re-esterified into TG and stored in adipose tissue. (omicsonline.org)
Atherosclerosis3
- R. J. Brown and D. J. Rader, "Lipases as modulators of atherosclerosis in murine models," Current Drug Targets , vol. 8, no. 12, pp. 1307-1319, 2007. (hindawi.com)
- Lipoprotein lipase for treating Atherosclerosis. (edoctoronline.com)
- Atherosclerosis is a disease process due to increased fat level in blood called as lipoproteins resulting deposition of these fat in the wall of the blood vessels causing narrowing/obstruction of the lumen of the blood vessels, as a result of which blood flow is compromised to the various organs of the body. (edoctoronline.com)
Hyperlipoproteinemia1
- Selective measurement of two lipase activities in post heparin plasma from normal subjects and patients with hyperlipoproteinemia. (nii.ac.jp)
Cardiovascular disease1
- Genest J, Libby P. Lipoprotein disorders and cardiovascular disease. (baptistjax.com)
Catabolism1
- Adipose triglyceride lipase and the lipolytic catabolism of cellular fat. (natrilha.info)
Mediates1
- It furthermore mediates the clearance of atherogenic remnant lipoproteins from the circulation. (ahajournals.org)
Triglyceride lipase activities1
- Although it has both phospholipase and triglyceride lipase activities it is primarily a triglyceride lipase with low but detectable phospholipase activity (PubMed:7592706, PubMed:12032167). (sdsc.edu)
Regulates2
- Tyrosine nitration after lipopolysaccharide (LPS) challenge down-regulates the lipase activity. (abcam.com)
- A celltype called as mast cells are present in the connective tissue layer which secrets/activates one enzyme called as lipoprotein lipase which regulates lipid entry/deposition/utilization into the walls of the blood vessels. (edoctoronline.com)
Monoclonal1
- Peterson, J.et al: Human lipoprotein lipase: relationship of activity, heparin affinity, and conformation as studied with monoclonal antibodies. (immuquest.com)