title: Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes.
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.
authors.affiliation: Obesity Research Center, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Hu
authors.forename: Jude T
authors.initials: JT
authors.lastname: Deeney
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nolan
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Peyot
authors.forename: Ada
authors.initials: A
authors.lastname: Ao
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Richard
authors.forename: Esthere
authors.initials: E
authors.lastname: Luc
authors.forename: Nils J
authors.initials: NJ
authors.lastname: Faergeman
authors.forename: Jens
authors.initials: J
authors.lastname: Knudsen
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.forename: Maria
authors.initials: M
authors.lastname: Sorhede-Winzell
authors.forename: Marc
authors.initials: M
authors.lastname: Prentki
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Corkey
mesh_terms: D000214:Acyl Coenzyme A / Q000494:pharmacology*; D017667:Adipocytes / Q000201:enzymology*; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D026261:Diazepam Binding Inhibitor / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology*; D008049:Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D002787:Sterol Esterase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D026261:Diazepam Binding Inhibitor; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D010171:Palmitoyl Coenzyme A; D002787:Sterol Esterase; D008049:Lipase