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)

Adipocytes hold the body's major energy reserve as triacylglycerols packaged in large lipid droplets. Perilipins, the most abundant proteins on these lipid droplets, play a critical role in facilitating both triacylglycerol storage and hydrolysis. The stimulation of lipolysis by beta-adrenergic agonists triggers rapid phosphorylation of perilipin and translocation of hormone-sensitive lipase to the surfaces of lipid droplets and more gradual fragmentation and dispersion of micro-lipid droplets. Because few lipid droplet-associated proteins have been identified in adipocytes, we isolated lipid droplets from basal and lipolytically stimulated 3T3-L1 adipocytes and identified the component proteins by mass spectrometry. Structural proteins identified in both preparations include perilipin, S3-12, vimentin, and TIP47; in contrast, adipophilin, caveolin-1, and tubulin selectively localized to droplets in lipolytically stimulated cells. Lipid metabolic enzymes identified in both preparations include hormone-sensitive lipase, lanosterol synthase, NAD(P)-dependent steroid dehydrogenase-like protein, acyl-CoA synthetase, long chain family member (ACSL) 1, and CGI-58. 17-beta-Hydroxysteroid dehydrogenase, type 7, was identified only in basal preparations, whereas ACSL3 and 4 and two short-chain reductase/dehydrogenases were identified on droplets from lipolytically stimulated cells. Additionally, both preparations contained FSP27, ribophorin I, EHD2, diaphorase I, and ancient ubiquitous protein. Basal preparations contained CGI-49, whereas lipid droplets from lipolytically stimulated cells contained several Rab GTPases and tumor protein D54. A close association of mitochondria with lipid droplets was suggested by the identification of pyruvate carboxylase, prohibitin, and a subunit of ATP synthase in the preparations. Thus, adipocyte lipid droplets contain specific structural proteins as well as lipid metabolic enzymes; the structural reorganization of lipid droplets in response to the hormonal stimulation of lipolysis is accompanied by increases in the relative mass of several proteins and the recruitment of additional proteins.
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PMID:Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes. 1533 53

The renin-angiotensin system is a key regulator of metabolism with beneficial effects of the angiotensin 1-7 (Ang 1-7) peptide. We hypothesized that the antiobesity effect of Ang 1-7 was related to the stimulation of brown adipose tissue (BAT). We administered Ang 1-7 (0.54 mg kg-1 day-1) for 28 days via implanted micro-osmotic pumps to mice with high-fat diet (HFD)-induced obesity. Ang 1-7 treatment reduced body weight, upregulated thermogenesis, and ameliorated impaired glucose homeostasis without affecting food consumption. Furthermore, Ang 1-7 treatment enlarged BAT and the increased expression of UCP1, PRDM16, and prohibitin. Alterations in PRDM16 expression correlated with increased AMPK and phosphorylation of mTOR. Ang 1-7 treatment elevated thermogenesis in subcutaneous white adipose tissue without altering UCP1 expression. These changes occurred in the context of decreased lipid accumulation in BAT from HFD-fed mice, preserved insulin signaling concomitant with phosphorylation of hormone-sensitive lipase and decreased expression of perilipin. These data suggest that Ang 1-7 induces brown adipocyte differentiation leading to upregulation of thermogenesis and improved metabolic profile in diet-induced obesity. Enhancing Ang 1-7 action represents a promising therapy to increase BAT and to reduce the metabolic complications associated with diet-induced obesity.
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PMID:Angiotensin 1-7 stimulates brown adipose tissue and reduces diet-induced obesity. 2906 63