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

Hu, LP; Deeney, JT; Nolan, CJ; Peyot, ML; Ao, A; Richard, AM; Luc, E; Faergeman, NJ; Knudsen, J and Guo, W, et al. (2005) In American Journal of Physiology: Endocrinology and Metabolism 289(6). p.1085-1092
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 mu M) 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... (More)
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 mu M) 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. (Less)
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keywords
acyl-coenzyme A-binding protein, hormone-sensitive, lipid signaling, lipase, free fatty acid
in
American Journal of Physiology: Endocrinology and Metabolism
volume
289
issue
6
pages
1085 - 1092
publisher
American Physiological Society
external identifiers
  • pmid:16091387
  • wos:000233558100021
  • scopus:33644676992
ISSN
1522-1555
DOI
10.1152/ajpendo.00210.2005
language
English
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yes
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4c235b48-cdab-4294-891b-93e11a6210c3 (old id 212384)
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2007-08-23 16:17:20
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2017-10-22 04:48:51
@article{4c235b48-cdab-4294-891b-93e11a6210c3,
  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 mu M) 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.},
  author       = {Hu, LP and Deeney, JT and Nolan, CJ and Peyot, ML and Ao, A and Richard, AM and Luc, E and Faergeman, NJ and Knudsen, J and Guo, W and Sörhede Winzell, Maria and Prentki, M and Corkey, BE},
  issn         = {1522-1555},
  keyword      = {acyl-coenzyme A-binding protein,hormone-sensitive,lipid signaling,lipase,free fatty acid},
  language     = {eng},
  number       = {6},
  pages        = {1085--1092},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Endocrinology and Metabolism},
  title        = {Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes},
  url          = {http://dx.doi.org/10.1152/ajpendo.00210.2005},
  volume       = {289},
  year         = {2005},
}