Differential regulation of adipocytokine mRNAs by rosiglitazone in db/db mice

The precise mechanism by which PPAR gamma activation by thiazolidinediones (TZDs) improves insulin sensitivity is still unclear. Recent studies have f ocused on the role of adipocytokines, in metabolic control and their regula tion by TZDs. In this study, we compared the chronic effects of antihypergl ycemic doses of the TZD rosiglitazone, the beta3-adrenoceptor agonist BRL-3 5135, and the PPAR alpha agonist Wy-14,643 on the m-RNA expression of adipo cytokines in WAT of db/db mice. Rosiglitazone treatment decreased adiponect in and resistin mRNA levels by 57 and 72%, respectively (P<0.001), with no effect on the level of TNF<alpha> or RELM alpha transcripts. In comparison, Wy-14,643 reduced adiponectin transcript levels by 31% (P=0.015) while BRL -35135 increased RELM alpha mRNA expression by 245% (P<0.001) without effec t on the other transcripts. Our results indicate that although a reduction in adiponectin and resistin mRNA levels in WAT by rosiglitazone treatment o f diabetic mice may contribute to the antidiabetic effects, an alteration i n TNF<alpha>, adiponectin, resistin, or RELMa mRNA expression is not absolu tely required for the regulation of blood glucose concentration in the db/d b mouse. (C) 2001 Academic Press.