Disease relevance of Lipe

• The increased body weight of OVX rat was paralleled by a greater retroperitoneal adipose tissue mass (P <.01), which was in turn associated with a marked rise in LPL activity (P <.005) and a slight decrease in HSL activity (P <.05) compared to intact animals [1].
• The level of adipose tissue lipoprotein lipase was decreased by hepatoma implantation and LPS injection, while the hormone-sensitive lipase activity was increased by the same treatments [2].
• Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxella TA144, an antarctic bacterium [3].
• The activity of adipose tissue hormone-sensitive lipase in animals with hyperinsulinemia has been reported to be increased compared with that in control animals [4].
• The results suggest that HSL is involved in the beta-cell responses to hyperglycemia and also in generating the lipid signal that is needed in stimulus-secretion coupling [5].

High impact information on Lipe

• Hormone-sensitive lipase, a key enzyme in fatty acid mobilization, overall energy homeostasis, and possibly steroidogenesis, is acutely controlled through reversible phosphorylation by catecholamines and insulin [6].
• The human hormone-sensitive lipase gene mapped to chromosome 19 cent-q13.3 [6].
• Insulin-mediated glucose and FFA uptake were reduced by 33% and 36%, respectively, whereas the activity of the catabolic enzyme hormone-sensitive lipase increased by 51% [7].
• Besides the catalytic site motif (Gly-Xaa-Ser-Xaa-Gly) found in most lipases, HSL shows no homology with other known lipases or proteins, except for a recently reported unexpected homology between the region surrounding its catalytic site and that of the lipase 2 of Moraxella TA144, an antarctic psychrotrophic bacterium [3].
• Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormone-sensitive lipase to the lipid storage droplet [8].

Chemical compound and disease context of Lipe

• Inhibition of HSL also reduced hyperglycemia in streptozotocin-induced diabetic rats [9].

Biological context of Lipe

• RESULTS: Exposure to rosiglitazone for 24 h induced ucp-1, lpl and hsl gene expression and when rosiglitazone was combined with insulin a synergistic effect on lpl and ucp-3 mRNA expression was produced [10].
• Hormone-sensitive lipase (HSL) is a rate-limiting enzyme in lipolysis that displays broad substrate specificity [11].
• HSL function is regulated by reversible phosphorylation that occurs within a 150 aa "regulatory module" of the protein [11].
• The current studies used mutational analysis to dissect the contribution of the "regulatory module" in HSL activity and substrate specificity [11].
• The HSL-to-LPL mRNA and activity ratios were enhanced from days 15 and 19 of pregnancy, respectively, and remained so even during lactation, mainly because of the marked lowering of the LPL values [12].

Anatomical context of Lipe

• Rosiglitazone up-regulates lipoprotein lipase, hormone-sensitive lipase and uncoupling protein-1, and down-regulates insulin-induced fatty acid synthase gene expression in brown adipocytes of Wistar rats [10].
• Lipoprotein lipase and hormone-sensitive lipase activity and mRNA in rat adipose tissue during pregnancy [12].
• Fasting alone increased activity in both the capillary-bound LPL and type L hormone-sensitive lipase (HSL) fractions of cardiac muscle [13].
• Exercise activates type L HSL in heart and skeletal muscle with a concomitant decrease in muscle TG stores [14].
• OVX-DHEA rats, compared to untreated OVX animals, had a smaller retroperitoneal fat depot, which correlated with a decrease in LPL activity (P <.005) and moderate increase in both HSL activity and beta3-AR density (P <.05) [1].

Associations of Lipe with chemical compounds

• Through its action, HSL is involved in regulating intracellular cholesterol metabolism and making unesterified cholesterol available for steroid hormone production [15].
• In the current studies we demonstrate a direct interaction of HSL with StAR using in vitro glutathione S-transferase pull-down experiments [15].
• These effects were consistent with increased LPL and HSL activities as well as respiration rates, mainly in response to exogenous palmitate [10].
• 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 [13].
• Relationship between type L hormone-sensitive lipase activity and endogenous triacylglycerol in the hearts of colchicine-treated rats [13].

Regulatory relationships of Lipe

• Growth hormone treatment combined with restricted high-fat feeding reduced the activity of both lipases in adipose tissue and stimulated hormone-sensitive lipase in muscle [16].

Other interactions of Lipe

• In contrast, neither turnover nor synthesis of imcTG in soleus was affected by fatty acid infusion (p>0.05). imcTG content and the activities of diglyceride acyltransferase and hormone sensitive lipase were not affected by fatty acid infusion [17].
• Chronic ethanol feeding also decreased beta-adrenergic receptor-stimulated protein kinase A activation and phosphorylation of its downstream proteins, perilipin A and hormone-sensitive lipase, the primary lipase-mediating lipolysis [18].
• A bolus infusion of 1 microg/rat leptin into the third cerebroventricle increased the expression of mRNA for hormone-sensitive lipase (HSL), an indicator of lipolysis, in white adipose tissue (WAT) [19].
• Two model substrates, rac-1-(3-phenoxy-[ring-14C]benzoyl)-2,3-dipalmitoyl glycerol (1(3PBA)DPG) and sn-2-(3-phenoxy-[ring-14C]benzoyl)-1,3-dipalmitoyl glycerol (2(3PBA)DPG), were compared with tri[1-14C]palmitoylglycerol or tri[9,10(n)-3H]oleoylglycerol as substrates for pancreatic lipase, lipoprotein lipase, and hormone-sensitive lipase [20].
• Hepatic acetyl-CoA carboxylase, beta-hydroxyacyl-CoA dehydrogenase, and adipose hormone-sensitive lipase activities were not affected by capsaicin feeding [21].

Analytical, diagnostic and therapeutic context of Lipe

• In this study, we used site-directed mutagenesis and two-dimensional phosphopeptide mapping to show that phosphorylation sites other than the previously identified Ser-563 are phosphorylated in HSL in response to isoproterenol stimulation of 32P-labeled rat adipocytes [22].
• Conglomerates of HSL molecules are in close association with the secretory granules of the beta-cell, as determined by immunoelectron microscopy with antibodies targeting two separate regions of HSL [23].
• Immunocytochemistry localized HSL to elongating spermatids and spermatozoa; HSL was not detected in interstitial cells [24].
• Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase [24].
• Perfusion with high concentrations of agent stimulate type L HSL activity, while perfusion with relatively low concentrations of agent inhibit enzyme activity [25].

References