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

The purpose of the present study was to examine the utilization of fatty acids (FA) and muscle substrates by skeletal muscle in young, middle-aged, and old adult rats under conditions of euglycemia with low insulin levels. Male Fischer 344 x Brown Norway rats aged 5, 15, or 24 mo underwent hindlimb perfusion with a medium of 8 mM glucose, 1 mM palmitate, 25 microU/ml insulin, [1-(14)C]palmitate, and [3-(3)H]glucose. Glucose and palmitate uptake were similar among age groups. The percent and total palmitate oxidized (nmol.min(-1).g(-1)) were 30-36 and 41-49% lower (P < 0.05) in 15-mo- and 24-mo-old than in 5-mo-old animals. Compared with 5-mo- and 15-mo-old animals, pre- and postperfusion muscle triglyceride (TG) levels were significantly (P < 0.05) elevated 91-305% in red and 118-219% in white muscles of 24-mo-old animals. Fatty acid-binding protein content was 40-64% higher (P < 0.05) in 24-mo- than in 5-mo- or 15-mo-old animals. In red muscle, hormone-sensitive lipase (HSL) content was 28% lower (P < 0.05) in 24-mo- than in 5-mo-old animals. These results indicate that, under euglycemic conditions in the presence of low insulin levels, the reduction in FA disposal to oxidation and the decrease in HSL content may contribute to the accumulation of TG in muscle of old animals.
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PMID:Impaired fatty acid oxidation in muscle of aging rats perfused under basal conditions. 1193 76

Adipose tissue is considered as the body's largest storage organ for energy in the form of triacylglycerols, which are mobilized through lipolysis process, to provide fuel to other organs and to deliver substrates to liver for gluconeogenesis (glycerol) and lipoprotein synthesis (free fatty acids). The release of glycerol and free fatty acids from human adipose tissue is mainly dependent on hormone-sensitive lipase which is intensively regulated by hormones and agents, such as insulin (inhibition of lipolysis) and catecholamines (stimulation of lipolysis). A special attention is paid to the recently discovered perilipins which could regulate the activity of the lipase hormono-sensible. Most of the plasma triacylglycerols are provided by dietary lipids, secreted from the intestine in the form of chylomicron or from the liver in the form of VLDL. Released into circulation as non-esterified fatty acids by lipoprotein lipase, those are taken up by adipose tissue via specific plasma fatty acid transporters (CD36, FATP, FABPpm) and used for triacylglycerol synthesis. A small part of triacylglycerols is synthesized into adipocytes from carbohydrates (lipogenesis) but its regulation is still debated in human. Physiological factors such as dieting/fasting regulate all these metabolic pathways, which are also modified in pathological conditions e.g. obesity.
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PMID:Metabolism of lipids in human white adipocyte. 1552 72

Uncoupling protein 3 (UCP3) expression is directly correlated to fatty acid oxidation in skeletal muscle. UCP3 has been hypothesized to facilitate high rates of fatty acid oxidation, but evidence thus far is lacking. Our aim was to investigate the effects of UCP3 overexpression and ablation on fatty acid uptake and metabolism in muscle of mice having congenic backgrounds. In mice constitutively expressing the UCP3 protein (human form) at levels just over twofold higher than normal (230% of wild-type levels), indirect calorimetry demonstrated no differences in total energy expenditure (VO2), but a shift toward increased fat oxidation compared with wild-type (WT) mice. Metabolic efficiency (gram weight gain/kcal ingested) was similar between Ucp3 overexpressors, WT and Ucp3 (-/-) mice. In muscle of Ucp3-tg mice, plasma membrane fatty acid binding protein (FABPpm) content was increased compared with WT mice. Although hormone-sensitive lipase activity was unchanged across the genotypes, there were increases in carnitine palmitoyltransferase I, beta-hydroxyacylCoA dehydrogenase, and citrate synthase activities and decreases in intramuscular triacylglycerol in muscle of Ucp3-tg mice. There were no differences in muscle mitochondrial content. High-energy phosphates and total muscle carnitine and CoA were also greater in Ucp3-tg compared with WT mice. Taken together, the findings demonstrate an increased capacity for fat oxidation in the absence of significant increases in thermogenesis in Ucp3-tg mice. Findings from Ucp3 (-/-) mice revealed few differences compared with WT mice, consistent with the possibility of compensatory mechanisms. In conjunction with our observed increases in CoA and carnitine in muscle of Ucp3 overexpressors, the findings support the hypothesized role for Ucp3 in facilitating fatty acid oxidation in muscle.
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PMID:Constitutive UCP3 overexpression at physiological levels increases mouse skeletal muscle capacity for fatty acid transport and oxidation. 1581 7

Fatty acid-binding proteins (FABPs) facilitate the diffusion of fatty acids within cellular cytoplasm. Compared with C57Bl/6J mice maintained on a high-fat diet, adipose-FABP (A-FABP) null mice exhibit increased fat mass, decreased lipolysis, increased muscle glucose oxidation, and attenuated insulin resistance, whereas overexpression of epithelial-FABP (E-FABP) in adipose tissue results in decreased fat mass, increased lipolysis, and potentiated insulin resistance. To identify the mechanisms that underlie these processes, real-time PCR analyses indicate that the expression of hormone-sensitive lipase is reduced, while perilipin A is increased in A-FABP/aP2 null mice relative to E-FABP overexpressing mice. In contrast, de novo lipogenesis and expression of genes encoding lipoprotein lipase, CD36, long-chain acyl-CoA synthetase 5, and diacylglycerol acyltransferase are increased in A-FABP/aP2 null mice relative to E-FABP transgenic animals. Consistent with an increase in de novo lipogenesis, there was an increase in adipose C16:0 and C16:1 acyl-CoA pools. There were no changes in serum free fatty acids between genotypes. Serum levels of resistin were decreased in the E-FABP transgenic mice, whereas serum and tissue adiponectin were increased in A-FABP/aP2 null mice and decreased in E-FABP transgenic animals; leptin expression was unaffected. These results suggest that the balance between lipolysis and lipogenesis in adipocytes is remodeled in the FABP null and transgenic mice and is accompanied by the reprogramming of adipokine expression in fat cells and overall changes in plasma adipokines.
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PMID:Lipid metabolism and adipokine levels in fatty acid-binding protein null and transgenic mice. 1630 44

PGC-1alpha overexpression in skeletal muscle, in vivo, has yielded disappointing and unexpected effects, including disrupted cellular integrity and insulin resistance. These unanticipated results may stem from an excessive PGC-1alpha overexpression in transgenic animals. Therefore, we examined the effects of a modest PGC-1alpha overexpression in a single rat muscle, in vivo, on fuel-handling proteins and insulin sensitivity. We also examined whether modest PGC-1alpha overexpression selectively targeted subsarcolemmal (SS) mitochondrial proteins and fatty acid oxidation, because SS mitochondria are metabolically more plastic than intermyofibrillar (IMF) mitochondria. Among metabolically heterogeneous rat hindlimb muscles, PGC-1alpha was highly correlated with their oxidative fiber content and with substrate transport proteins (GLUT4, FABPpm, and FAT/CD36) and mitochondrial proteins (COXIV and mTFA) but not with insulin-signaling proteins (phosphatidylinositol 3-kinase, IRS-1, and Akt2), nor with 5'-AMP-activated protein kinase, alpha2 subunit, and HSL. Transfection of PGC-1alpha into the red (RTA) and white tibialis anterior (WTA) compartments of the tibialis anterior muscle increased PGC-1alpha protein by 23-25%. This also induced the up-regulation of transport proteins (FAT/CD36, 35-195%; GLUT4, 20-32%) and 5'-AMP-activated protein kinase, alpha2 subunit (37-48%), but not other proteins (FABPpm, IRS-1, phosphatidylinositol 3-kinase, Akt2, and HSL). SS and IMF mitochondrial proteins were also up-regulated, including COXIV (15-75%), FAT/CD36 (17-30%), and mTFA (15-85%). PGC-1alpha overexpression also increased palmitate oxidation in SS (RTA, +116%; WTA, +40%) but not in IMF mitochondria, and increased insulin-stimulated phosphorylation of AKT2 (28-43%) and rates of glucose transport (RTA, +20%; WTA, +38%). Thus, in skeletal muscle in vivo, a modest PGC-1alpha overexpression up-regulated selected plasmalemmal and mitochondrial fuel-handling proteins, increased SS (not IMF) mitochondrial fatty acid oxidation, and improved insulin sensitivity.
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PMID:Modest PGC-1alpha overexpression in muscle in vivo is sufficient to increase insulin sensitivity and palmitate oxidation in subsarcolemmal, not intermyofibrillar, mitochondria. 1807 23