Omega-3-polyunsaturated fatty acids (ω-3-PUFAs) have well-documented protective effects that are attributed not only to eicosanoid inhibition but also to the formation of novel biologically active lipid mediators ( i.e. , resolvins and protectins). In this study, we examined their effects on ob/ob mice, an obesity model of insulin resistance and fatty liver disease. Dietary intake of ω-3-PUFAs had insulin-sensitizing actions in adipose tissue and liver and improved insulin tolerance in obese mice. Genes involved in insulin sensitivity (PPARγ), glucose transport (GLUT-2/GLUT-4), and insulin receptor signaling (IRS-1/IRS-2) were up-regulated by ω-3-PUFAs. Moreover, ω-3-PUFAs increased adiponectin, an anti-inflammatory and insulin-sensitizing adipokine, and induced AMPK phosphorylation, a fuel-sensing enzyme and a gatekeeper of the energy balance. Concomitantly, hepatic steatosis was alleviated by ω-3-PUFAs. A lipidomic analysis with liquid chromatography/mass spectrometry/mass spectrometry revealed that ω-3-PUFAs inhibited the formation of ω-6-PUFA-derived eicosanoids, while triggering the formation of ω-3-PUFA-derived resolvins and protectins. Moreover, representative members of these lipid mediators, namely resolvin E1 and protectin D1, mimicked the insulin-sensitizing and antisteatotic effects of ω-3-PUFAs and induced adiponectin expression to a similar extent that of rosiglitazone, a member of the thiazolidinedione family of antidiabetic drugs. Taken together, these findings uncover beneficial actions of ω-3-PUFAs and their bioactive lipid autacoids in preventing obesity-induced insulin resistance and hepatic steatosis.—González-Périz, A., Horrillo, R., Ferré, N., Gronert, K., Dong, B., Morán-Salvador, E., Titos, E., Martínez-Clemente, M., López-Parra, M., Arroyo, V., Clària, J. Obesity-induced insulin resistance and hepatic steatosis are alleviated by ω-3 fatty acids: a role for resolvins and protectins.
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Obesity-induced insulin resistance and hepatic steatosis are alleviated by ω-3 fatty acids: a role for resolvins and protectins
González-Périz, Ana; Horrillo, Raquel; Ferré, Natàlia; Gronert, Karsten; Dong, Baiyan; Morán-Salvador, Eva; Titos, Esther; Martínez-Clemente, Marcos; López-Parra, Marta; Arroyo, Vicente; Clària, Joan
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, Volume 23 (6): 1946
Fed of American Socs for Experimental Biology – Jun 1, 2009
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