Stimulation by eicosapentaenoic acids of leptin mRNA expression and its secretion in mouse 3T3-L1 adipocytes in vitro

Recent evidence indicates that both leptin and eicosapentaenoic acids (EPA) improve insulin sensitivity. In the present study, we examined the effect of EPA on endogenous leptin expression in 3T3-L1 adipocytes to clarify whet her the EPA's effect is exerted through leptin expression. EPA caused a tim e- and dose-dependent increase of leptin mRNA levels in 3T3-L1 adipocytes. Leptin mRNA expression was significantly increased up to 309.4 +/- 17.0% of the control by 24 h (P < 0.01; n = 6), Leptin secretion was also significa ntly increased up to 193.3 +/- 12.1% of the control by 24 h (P < 0.01; n = 6). EPA is a ligand for peroxisome proliferator-activated receptors (PPARs) with the highest affinity to PPAR alpha. We examined the effect on leptin expression of clofibrate, a ligand for PPAR alpha, bezafibrate, for PPAR be ta, or troglitazone, for PPAR gamma, to clarify whether these ligands for P PARs could mimic EPA-induced stimulation of leptin expression. Neither clof ibrate nor bezafibrate affected leptin mRNA expression, whereas troglitazon e significantly suppressed leptin mRNA expression. On the other hand, inhib ition by 6-diazo-5-oxo-L-norleucine of the rate-limiting enzyme in hexosami ne biosynthesis blunted EPA-induced stimulation of leptin mRNA expression a nd its secretion. These data suggest that EPA upregulates leptin gene expre ssion and its secretion probably through a hexosamine biosynthetic pathway. (C) 2000 Academic Press.