Eicosapentaenoic Acid and Rosiglitazone Increase Adiponectin in an Additive and PPARgamma-Dependent Manner in Human Adipocytes.

Obesity (Silver Spring). 2010 Sep 2. [Epub ahead of print]

Eicosapentaenoic Acid and Rosiglitazone Increase Adiponectin in an Additive and PPARgamma-Dependent Manner in Human Adipocytes.
Tishinsky JM, Ma DW, Robinson LE.

Department of Human Health and Nutritional Sciences, Animal Science and Nutrition Building, University of Guelph, Guelph, Ontario, Canada.

Abstract
Adiponectin, an anti-inflammatory and insulin-sensitizing protein secreted from adipose tissue, may be modulated by dietary fatty acids, although the mechanism is not fully known. Our objective was to investigate the effect of long-chain n-3 polyunsaturated fatty acids (PUFAs) on adiponectin in cultured human adipocytes, and to elucidate the role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in this regulation. Isolated human adipocytes were cultured for 48 h with 100 micromol/l eicosapentaenoic acid (C20:5n-3, EPA), docosahexaenoic acid (C22:6n-3, DHA), palmitic acid (C16:0), 100 micromol/l EPA plus 100 micromol/l DHA, or bovine serum albumin (control). Additionally, adipocytes were treated for 48 h with a PPARgamma antagonist (BADGE) or agonist (rosiglitazone) in isolation or in conjunction with either EPA or DHA. At 48 h, EPA and DHA increased (P < 0.05) adiponectin secretion by 88 and 47%, respectively, while EPA, but not DHA, also increased (136%, P < 0.001) cellular adiponectin protein. Interestingly, PPARgamma antagonism completely abolished the DHA-mediated increase in secreted adiponectin, but only partially attenuated the EPA-mediated response. Thus, EPA's effects on adiponectin do not appear to be entirely PPARgamma mediated. Rosiglitazone increased (P < 0.001) the secreted and cellular adiponectin protein (90 and 582%, respectively). Finally, the effects of EPA and rosiglitazone on adiponectin secretion were additive (+230% at 48 h combined, compared to 121 and 124% by EPA or rosiglitazone alone, respectively). Overall, our findings emphasize the therapeutic importance of long-chain n-3 PUFA alone, or in combination with a PPARgamma agonist, as a stimulator of adiponectin, a key adipokine involved in obesity and related diseases.