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)

We established a cell-free system in which epinephrine and other lipolytic agents stimulated lipolysis of endogenous lipid droplets from fat cells by hormone-sensitive lipase. The endogenous lipid droplets were prepared by hypotonic treatment of fat cells and their successive washing with buffer containing 0.025% Triton X-100. In the cell-free system, propranolol inhibited lipolysis induced by various lipolytic agents such as norepinephrine, theophylline and cyclic AMP (cAMP), whereas phenoxybenzamine did not inhibit lipolysis. The binding of these lipolytic agents to endogenous lipid droplets was inhibited by propranolol, but not by phenoxybenzamine. The "propranolol-sensitive" binding of these lipolytic agents to the droplets may be involved in lipolysis. Treatment of the droplets with phospholipase C, but not phospholipase D, inhibited the propranolol-sensitive binding of these lipolytic agents to the droplets. These results suggest that the phosphate group of phospholipid in the droplets may be the site of propranolol-sensitive of binding of theophylline, and cAMP in addition to norepinephrine.
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PMID:Propranolol-sensitive binding of lipolytic agents to lipid droplets from adipocytes. 165 19

The amount of fatty acid release by a fat cell homogenate without pretreatment with epinephrine was found to be slightly more than that released from fat cells by epinephrine, suggesting that fat cells contain high lipolytic activity even in the absence of lipolytic agents. Fat cells contain high hormone-sensitive lipase activity (1383 mumole free fatty acids/g/hr) in the absence of epinephrine, and addition of epinephrine to the cells did not increase the activity, significantly. Like epinephrine, DBcAMP and/or theophylline also elicited marked release of glycerol from fat cells without activating the hormone-sensitive lipase activity. However, although fat cells contain a large amount of hormone-sensitive lipase, lipolysis was negligible in the absence of these lipolytic agents. These results suggest that lipolytic agents such as epinephrine, DBcAMP, and theophylline induce lipolysis in fat cells through some mechanism other than activation of hormone-sensitive lipase and that in the absence of lipolytic agents, some system in fat cells inhibits lipolysis of endogenous lipid droplets by hormone-sensitive lipase. The lipid droplets in fat cells consist mainly of triglyceride with phospholipids, cholesterol, carbohydrate, and protein as minor constituents. The phospholipid fraction was found to consist of 75% phosphatidylcholine and 25% phosphatidylethanolamine. Of the minor constituents of endogenous lipid droplets, only phosphatidylcholine strongly inhibited hormone-sensitive lipase activity in a [3H]triolein emulsion. These results suggest that phosphatidylcholine in endogenous lipid droplets may be responsible for inhibition of hormone-sensitive lipase. Then, a cell-free system was established in which epinephrine, DBcAMP, and theophylline stimulated lipolysis of endogenous lipid droplets from fat cells by lipase solution. In this system, these lipolytic agents did not induce lipolysis in the absence of added lipase. Lipolysis in the mixture of the endogenous lipid droplets and lipase solution was accelerated by phospholipase C with concomitant loss of epinephrine-induced lipolysis. After pretreatment of the endogenous lipid droplets with phospholipase C, these lipolytic agents no longer induced lipolysis. Pretreatment of the endogenous lipid droplets with phospholipase C reduced their phospholipid content with the formation of phosphorylcholine, but did not affect their triglyceride and cholesterol contents. Treatment of the endogenous lipid droplets with phospholipase D did not affect lipolysis in the cell-free system. These results suggest that phosphatidylcholine in the endogenous lipid droplets may inhibit their lipolysis by hormone-sensitive lipase in fat cells and also be involved in the mechanisms of the stimulatory effects of epinephrine, DBcAMP, and theophylline on lipolysis.
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PMID:Biomodulator-mediated susceptibility of endogenous lipid droplets from rat adipocytes to hormone-sensitive lipase. 216 Dec 47

The lipolytic action of theophylline was examined using both intact fat cells and a fat globule system. Theophylline had similar lipolytic actions in both systems. However theophylline did not activate hormone-sensitive lipase in the fat globule system as measured with added Ediol. Pretreatment of the fat globules with phospholipase C suppressed theophylline-induced lipolysis, but phospholipase D had no effect. A theophylline-sensitive system was reconstituted from endogenous fat and a lipase fraction. Inhibitors of theophylline-induced lipolysis such as quinine and propranolol inhibited theophylline binding to artificial lipid micelles. Purine nucleosides such as adenosine, inosine and guanosine inhibited theophylline-induced lipolysis in the fat globule system. These results suggest that theophylline has a lipolytic action similar to that of adrenaline. Both share a lipolytic mechanism additional to that involving the activation of hormone sensitive lipase through the cyclic-AMP dependent protein kinase. Phospholipids play an important role in this additional mechanism.
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PMID:The mechanism of the lipolytic action of theophylline in fat cells. 724 46