Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.79 (hormone-sensitive lipase)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colchicine injection was used as a tool to potentiate the increase in intracellular lipoprotein lipase (type L hormone-sensitive lipase) activity normally seen with fasting to determine if elevation of enzyme activity by this method produced a reduction in endogenous triacylglycerol (TG) in rat heart. Both fasting and fasting+colchicine treatment increased total lipoprotein lipase (LPL) activity from a control value of 80 units/g to approx. 144 units/g. The initial control value was obtained at 08:00 h after overnight feeding and the final values were obtained at 17:00 h, after 9 h of fasting. Fasting alone increased activity in both the capillary-bound LPL and type L hormone-sensitive lipase (HSL) fractions of cardiac muscle. In contrast, colchicine treatment, by blocking the export of enzyme from the cell as a result of microtubular disruption, restricted the increase in enzyme activity to the intracellular fraction of the heart. There was a highly significant (P less than 0.001) negative relationship (r = -0.73) between type L HSL activity and TG content in hearts of fasting and fasting+colchicine-treated rats. At a time when type L HSL activity was increased and TG content decreased, the cyclic AMP concentration of heart remained unchanged, ruling out the possibility that cyclic AMP might be activating any one of the identified cardiac TG lipases. These data provided indirect evidence that type L HSL is 'seeing the intracellular TG droplet' and that this enzyme may play a role in the regulation of myocardial lipolysis.
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PMID:Relationship between type L hormone-sensitive lipase activity and endogenous triacylglycerol in the hearts of colchicine-treated rats. 609 67

Adipocyte triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are intracellular lipases that mobilize triglycerides, the main energy source in mammals. Deletion of genes encoding ATGL (Pnpla2) or HSL (Lipe) in mice results in striking phenotypic differences, suggesting distinct roles for these lipases. The goal of the present study was to identify the biological processes that are modulated in the metabolic tissues of ATGL- and HSL-deficient mice. DNA microarrays were employed to provide full genome coverage concerning the types of genes that are differentially expressed in wild-type and mutant mice. For both mouse models, transcript signatures were identified in white adipose tissue, brown adipose tissue (BAT), skeletal muscle (SM), cardiac muscle (CM), and liver. Genetic ablation of ATGL and HSL alters the transcript levels of a large number of genes in metabolic tissues. The genes affected in the two models are, however, largely different ones. Indeed, only one biological process was modulated in the same way in both mouse models, namely the down-regulation of fatty acid metabolism in BAT. The most pronounced modulation of biological processes was observed in ATGL-/- CM, in which a concerted down-regulation of transcripts associated with oxidative pathways was observed. In HSL-/- mice, in contrast, the most marked changes were seen in SM, namely, alterations in transcript levels reflecting a change of energy source from lipid to carbohydrate. The transcript signatures also provided novel insights into the metabolic derangements that are characteristic of ATGL-/- mice. Our findings suggest that ATGL and HSL differentially modulate biological processes in metabolic tissues. We hypothesize that the intermediary metabolites of the lipolytic pathways are signaling molecules and activators of a wide range of biochemical and cellular processes in mammals.
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PMID:Differential transcriptional modulation of biological processes in adipocyte triglyceride lipase and hormone-sensitive lipase-deficient mice. 1857

Fatty acids (FAs) are essential components of all lipid classes and pivotal substrates for energy production in all vertebrates. Additionally, they act directly or indirectly as signaling molecules and, when bonded to amino acid side chains of peptides, anchor proteins in biological membranes. In vertebrates, FAs are predominantly stored in the form of triacylglycerol (TG) within lipid droplets of white adipose tissue. Lipid droplet-associated TGs are also found in most nonadipose tissues, including liver, cardiac muscle, and skeletal muscle. The mobilization of FAs from all fat depots depends on the activity of TG hydrolases. Currently, three enzymes are known to hydrolyze TG, the well-studied hormone-sensitive lipase (HSL) and monoglyceride lipase (MGL), discovered more than 40 years ago, as well as the relatively recently identified adipose triglyceride lipase (ATGL). The phenotype of HSL- and ATGL-deficient mice, as well as the disease pattern of patients with defective ATGL activity (due to mutation in ATGL or in the enzyme's activator, CGI-58), suggest that the consecutive action of ATGL, HSL, and MGL is responsible for the complete hydrolysis of a TG molecule. The complex regulation of these enzymes by numerous, partially uncharacterized effectors creates the "lipolysome," a complex metabolic network that contributes to the control of lipid and energy homeostasis. This review focuses on the structure, function, and regulation of lipolytic enzymes with a special emphasis on ATGL.
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PMID:Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. 1895 73

Neutral lipid storage disease is caused by mutations in the CGI-58 or the PNPLA2 genes. Lipid storage can be detected in various cell types including blood granulocytes. While CGI-58 mutations are associated with Chanarin-Dorfman syndrome, a condition characterized by lipid storage and skin involvement (ichthyosis), mutations in the patatin-like phospholipase domain-containing protein 2 gene (PNPLA2) were reported with skeletal and cardiac muscle disease only. We describe clinical, myopathological, magnetic resonance imaging (MRI), and genetic findings of six patients carrying different recessive PNPLA2 mutations. Pulse-chase labeling of control and patient cells with supplementation of clenbuterol, salmeterol, and dexamethasone was performed in vitro. The patients share a recognizable phenotype with prominent shoulder girdle weakness and mild pelvic girdle and distal muscle weakness, with highly elevated creatine kinase (CK) and cardiomyopathy developing at later stages. Muscle histology invariably reveals massive accumulation of lipid droplets. New muscle or whole-body MRI techniques may assist diagnosis and may become a useful tool to quantify intramuscular lipid storage. Four novel and two previously reported mutations were detected, affecting different parts of the PNPLA2 gene. Activation of hormone-sensitive lipase by beta-adrenergic substances such as clenbuterol appears to bypass the enzymatic block in PNPLA2-deficient patient cells in vitro. PNPLA2 deficiency is a slowly progressive myopathy with onset around the third decade. Cardiac involvement is relatively common at a later stage. Muscle MRI may detect increased lipid in a characteristic distribution, which could be used for monitoring disease progression. Beta-adrenergic agents may be beneficial in improving triacylglycerol breakdown in patients with PNPLA2 mutations.
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PMID:The phenotypic spectrum of neutral lipid storage myopathy due to mutations in the PNPLA2 gene. 2154 67

Leptin is a hormone secreted primarily by adipose tissue and its blood levels depend on the amount of fat stored in adipocytes. Leptin has a wide range of physiological effects. Acting directly or through the sympathetic nervous system it participates in the regulation of energy metabolism. Leptin inhibits synthesis of triacylglycerols in the liver, adipose tissue and skeletal muscles, thus reducing the intracellular lipid content in these tissues. In adipocytes, leptin down-regulates the expression of genes encoding fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), the major enzymes of fatty acid synthesis, while it up-regulates the expression of the hormone-sensitive lipase (HSL) encoding gene, thus stimulating hydrolysis of triacylglycerols in adipose tissue. Moreover, leptin enhances fatty acid oxidation in adipocytes, and skeletal and cardiac muscle by increasing the expression of genes encoding key enzymes involved in this process, carnitine palmitoyltransferase 1 (CPT1) and medium chain acyl-CoA dehydrogenase (MCAD). It has also been demonstrated that this hormone improves insulin sensitivity and glucose tolerance by stimulating glucose transport and metabolism in many tissues. It is known that leptin is involved in the long-term regulation of food intake. However, increasing evidence suggests that it may also influence energy substrate utilization in peripheral tissues. Therefore, leptin can effectively control whole-body energy homeostasis by altering lipid and carbohydrate metabolism, especially in adipose tissue and muscles.
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PMID:[Role of leptin in the regulation of lipid and carbohydrate metabolism]. 2167 50

Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL and its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 expression increases cellular TG content and Plin5-deficient mice exhibit reduced cardiac TG levels. In this study we show that mice with cardiac muscle-specific overexpression of perilipin 5 (CM-Plin5) massively accumulate TG in CM, which is accompanied by moderately reduced fatty acid (FA) oxidizing gene expression levels. Cardiac lipid droplet (LD) preparations from CM of CM-Plin5 mice showed reduced ATGL- and hormone-sensitive lipase-mediated TG mobilization implying that Plin5 overexpression restricts cardiac lipolysis via the formation of a lipolytic barrier. To test this hypothesis, we analyzed TG hydrolytic activities in preparations of Plin5-, ATGL-, and CGI-58-transfected cells. In vitro ATGL-mediated TG hydrolysis of an artificial micellar TG substrate was not inhibited by the presence of Plin5, whereas Plin5-coated LDs were resistant toward ATGL-mediated TG catabolism. These findings strongly suggest that Plin5 functions as a lipolytic barrier to protect the cardiac TG pool from uncontrolled TG mobilization and the excessive release of free FAs.
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PMID:Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier. 2341 37