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This Article Full Text Full Text (PDF) All Versions of this Article: 292/4/E1223    most recent 00446.2006v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Le Foll, C. Articles by Delarue, J. Search for Related Content PubMed PubMed Citation Articles by Le Foll, C. Articles by Delarue, J.

Long-chain n-3 polyunsaturated fatty acids dissociate phosphorylation of Akt from phosphatidylinositol 3'-kinase activity in rats

¹Equipe d'Accueil "Oxylipides", Faculté de Médecine, Brest; ²Département Génie Alimentaire, Ifremer, Nantes; and ³Equipe d'Accueil "Oxylipides" & Laboratoire Régional de Nutrition Humaine, Faculté de Médecine, Centre Hospitalo-Universitaire, Brest, France

Submitted 24 August 2006 ; accepted in final form 11 December 2006

We examined whether a low amount of dietary long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) modulated phosphatidylinositol 3'-kinase (PI 3-kinase) activity and downstream Akt phosphorylation differently in normal or insulin-resistant rats. Rats were fed for 28 days with either a control diet containing 14.6% of metabolizable energy (ME) as peanut-rape oil (PR) or an n-3 diet where 4.9% of ME as PR was replaced by fish oil. Over the last 5 days, rats received 9 NaCl or dexamethasone (1 mg/kg). Insulin stimulation of both PI 3-kinase activity and Akt serine⁴⁷³ phosphorylation and modulation of GLUT4 content were studied in liver, muscle, and adipose tissue (AT). Glucose tolerance and insulin sensitivity were determined by an oral glucose challenge. In muscle and AT, LC n-3 PUFA abolished insulin-stimulated PI 3-kinase activity. These effects were not paralleled by defects in Akt serine⁴⁷³ phosphorylation, which was even increased in AT. Dexamethasone abolished insulin-stimulated PI 3-kinase activity in all tissues, whereas Akt serine⁴⁷³ phosphorylation was markedly reduced in muscle but unaltered in liver and AT. Such tissue-specific dissociating effects of LC n-3 PUFA on PI 3-kinase/Akt activation took place without alteration of glucose metabolism. Maintenance of a normal glucose metabolism by the n-3 diet despite abolition of PI 3-kinase activation was likely explained by a compensatory downstream Akt serine⁴⁷³ phosphorylation. The inability of LC n-3 PUFA to prevent insulin resistance by dexamethasone could result from the lack of such a dissociation.

eicosapentaenoic acid; docosahexaenoic acid; insulin resistance; dexamethasone

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