Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes

• Published in: American journal of physiology: endocrinology and metabolism 2005-12, Vol.289 (6), p.E1085-E1092
• Main Authors: Hu, Liping, Deeney, Jude T, Nolan, Christopher J, Peyot, Marie-Line, Ao, Ada, Richard, Ann Marie, Luc, Esthere, Faergeman, Nils J, Knudsen, Jens, Guo, Wen, Sorhede-Winzell, Maria, Prentki, Marc, Corkey, Barbara E
• Format: Article
• Language: English
• Subjects: Acyl Coenzyme A - pharmacology; acyl-coenzyme A-binding protein; Adipocytes - enzymology; Animals; Basic Medicine; Cytosol - enzymology; Diazepam Binding Inhibitor - pharmacology; Enzyme Inhibitors - pharmacology; Fatty Acids, Nonesterified - metabolism; free fatty acid; Fysiologi; hormone-sensitive; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - enzymology; lipase; Lipase - antagonists & inhibitors; Lipase - metabolism; lipid signaling; Lipolysis - drug effects; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Inbred C57BL; Mice, Knockout; Palmitoyl Coenzyme A - pharmacology; Phosphorylation; Physiology; Rats; Rats, Sprague-Dawley; Signal Transduction; Sterol Esterase - antagonists & inhibitors; Sterol Esterase - deficiency; Sterol Esterase - metabolism; Triglycerides - metabolism
• ISSN: 0193-1849; 1522-1555; 1522-1555
• DOI: 10.1152/ajpendo.00210.2005

1 Obesity Research Center, Boston University School of Medicine, Boston, Massachusetts; 2 Molecular Nutrition Unit, Department of Nutrition, University of Montreal, Centre de Recherche du Centre Hospitalier de l’Université Montreál, and the Montreal Diabetes Research Center, Montreal, Quebec, Canada; 3 Department of Endocrinology and Diabetes, The Canberra Hospital, and the Australian National University Medical School, Canberra, ACT, Australia; 4 Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark; and 5 Department of Medicine, Lund University, Lund, Sweden Submitted 10 May 2005 ; accepted in final form 3 August 2005 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 -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 µM) 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. acyl-coenzyme A-binding protein; free fatty acid; hormone-sensitive lipase; lipid signaling Address for reprint requests and other correspondence: B. E. Corkey, Obesity Research Cen