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Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2005 Dec; Vol. 289 (6), pp. E1085-92. Date of Electronic Publication: 2005 Aug 09. - Publication Year :
- 2005
-
Abstract
- Intracellular lipolysis is a major pathway of lipid metabolism that has roles, not only in the provision of free fatty acids as energy substrate, but also in intracellular signal transduction. The latter is likely to be particularly important in the regulation of insulin secretion from islet beta-cells. The mechanisms by which lipolysis is regulated in different tissues is, therefore, of considerable interest. Here, the effects of long-chain acyl-CoA esters (LC-CoA) on lipase activity in islets and adipocytes were compared. Palmitoyl-CoA (Pal-CoA, 1-10 microM) stimulated lipase activity in islets from both normal and hormone-sensitive lipase (HSL)-null mice and in phosphatase-treated islets, indicating that the stimulatory effect was neither on HSL nor phosphorylation dependent. In contrast, we reproduced the previously published observations showing inhibition of HSL activity by LC-CoA in adipocytes. The inhibitory effect of LC-CoA on adipocyte HSL was dependent on phosphorylation and enhanced by acyl-CoA-binding protein (ACBP). In contrast, the stimulatory effect on islet lipase activity was blocked by ACBP, presumably due to binding and sequestration of LC-CoA. These data suggest the following intertissue relationship between islets and adipocytes with respect to fatty acid metabolism, LC-CoA signaling, and lipolysis. Elevated LC-CoA in islets stimulates lipolysis to generate a signal to increase insulin secretion, whereas elevated LC-CoA in adipocytes inhibits lipolysis. Together, these opposite actions of LC-CoA lower circulating fat by inhibiting its release from adipocytes and promoting fat storage via insulin action.
- Subjects :
- Animals
Cytosol enzymology
Diazepam Binding Inhibitor pharmacology
Enzyme Inhibitors pharmacology
Fatty Acids, Nonesterified metabolism
Insulin metabolism
Insulin Secretion
Lipase antagonists & inhibitors
Mice
Mice, Inbred C57BL
Mice, Knockout
Palmitoyl Coenzyme A pharmacology
Phosphorylation
Rats
Rats, Sprague-Dawley
Signal Transduction
Sterol Esterase antagonists & inhibitors
Sterol Esterase deficiency
Sterol Esterase metabolism
Triglycerides metabolism
Acyl Coenzyme A pharmacology
Adipocytes enzymology
Islets of Langerhans enzymology
Lipase metabolism
Lipolysis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0193-1849
- Volume :
- 289
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 16091387
- Full Text :
- https://doi.org/10.1152/ajpendo.00210.2005