31 Hu, L. Deeney, J. T. Nolan, C. J. Peyot, M. L. Ao, A. Richard, A. M. Luc, E. Faergeman, N. J. Knudsen, J. Guo, W. Sorhede-Winzell, M. Prentki, M. Corkey, B. E. 2005 Am J Physiol Endocrinol Metab 289 6 E1085-92 Dec 0193-1849 (Print) 16091387 Islets of Langerhans/*enzymology Insulin/secretion Fatty Acids, Nonesterified/metabolism Enzyme Inhibitors/pharmacology Diazepam Binding Inhibitor/pharmacology Cytosol/enzymology Animals Adipocytes/*enzymology Acyl Coenzyme A/*pharmacology Triglycerides/metabolism Sterol Esterase/antagonists & inhibitors/deficiency/metabolism Signal Transduction Rats, Sprague-Dawley Rats Phosphorylation Palmitoyl Coenzyme A/pharmacology Mice, Knockout Mice, Inbred C57BL Mice Lipolysis/*drug effects Lipase/antagonists & inhibitors/*metabolism Fatty Acids Nonesterified/metabolism Sprague-Dawley Knockout Inbred C57BL 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. DK 35914/DK/NIDDK NIH HHS/United StatesDK 42600/DK/NIDDK NIH HHS/United StatesDK 56690/DK/NIDDK NIH HHS/United StatesDK 63356/DK/NIDDK NIH HHS/United StatesComparative StudyJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tUnited States http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16091387