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This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/E923    most recent 00555.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by González-Yanes, C. Articles by Sánchez-Margalet, V. Search for Related Content PubMed PubMed Citation Articles by González-Yanes, C. Articles by Sánchez-Margalet, V.

Oleylethanolamide impairs glucose tolerance and inhibits insulin-stimulated glucose uptake in rat adipocytes through p38 and JNK MAPK pathways

¹Department of Medical Biochemistry and Molecular Biology, School of Medicine, Investigation Unit, Virgen Macarena University Hospital, Seville, Spain; and ²Investigation Unit, Mediterranean Institute for the Advancement of Biotechnology and Sanitary Research, Hospital Carlos Haya, Malaga, Spain

Submitted 19 November 2004 ; accepted in final form 28 April 2005

Oleylethanolamide (OEA) is a lipid mediator that inhibits food intake and body weight gain and also exhibits hypolipemiant actions. OEA exerts its anorectic effects peripherally through the stimulation of C-fibers. OEA is synthesized in the intestine in response to feeding, increasing its levels in portal blood after the meal. Moreover, OEA is produced by adipose tissue, and a lipolytic effect has been found. In this work, we have examined the effect of OEA on glucose metabolism in rats in vivo and in isolated adipocytes. In vivo studies showed that acute administration (30 min and 6 h) of OEA produced glucose intolerance without decreasing insulin levels. Ex vivo, we found that 10 min of preincubation with OEA inhibited 30% insulin-stimulated glucose uptake in isolated adipocytes. Maximal effect was achieved at 1 µM OEA. The related compounds palmitylethanolamide and oleic acid had no effect, suggesting a specific mechanism. Insulin-stimulated GLUT4 translocation was not affected, but OEA promoted Ser/Thr phosphorylation of GLUT4, which may impair transport activity. This phosphorylation may be partly mediated by p38 and JNK kinases, since specific inhibitors (SB-203580 and SP-600125) partly reverted the inhibitory effect of OEA on insulin-stimulated glucose uptake. These results suggest that the lipid mediator OEA inhibits insulin action in the adipocyte, impairing glucose uptake via p38 and JNK kinases, and these effects may at least in part explain the glucose intolerance produced in rats in vivo. These effects of OEA may contribute to the anorectic effects induced by this mediator, and they might be also relevant for insulin resistance in adipose tissue.

lipid mediators; fatty acid ethaloamides; insulin action; signaling; c-Jun amino-terminal kinase; mitogen-activated protein kinase