Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins.

Abstract

Omega-3-polyunsaturated fatty acids (omega-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 omega-3-PUFAs had insulin-sensitizing actions in adipose tissue and liver and improved insulin tolerance in obese mice. Genes involved in insulin sensitivity (PPARgamma), glucose transport (GLUT-2/GLUT-4), and insulin receptor signaling (IRS-1/IRS-2) were up-regulated by omega-3-PUFAs. Moreover, omega-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 omega-3-PUFAs. A lipidomic analysis with liquid chromatography/mass spectrometry/mass spectrometry revealed that omega-3-PUFAs inhibited the formation of omega-6-PUFA-derived eicosanoids, while triggering the formation of omega-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 omega-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 omega-3-PUFAs and their bioactive lipid autacoids in preventing obesity-induced insulin resistance and hepatic steatosis.

• Authors: Ana González-Périz, Raquel Horrillo, Natàlia Ferré, Karsten Gronert, Baiyan Dong, Eva Morán-Salvador, Esther Titos, Marcos Martínez-Clemente, Marta López-Parra, Vicente Arroyo, Joan Clària
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 23 Issue 6 Pg. 1946-57 (Jun 2009) ISSN: 1530-6860 [Electronic] United States
• PMID: 19211925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Chemokine CCL2
• Dietary Fats
• Fatty Acids, Omega-3
• Glucose Transporter Type 4
• Hypoglycemic Agents
• Insulin Receptor Substrate Proteins
• Irs1 protein, mouse
• PPAR gamma
• Resistin
• Slc2a4 protein, mouse
• Thiazolidinediones
• protectin D1
• Rosiglitazone
• Docosahexaenoic Acids
• Eicosapentaenoic Acid
• AMP-Activated Protein Kinases
• 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid

Topics

• AMP-Activated Protein Kinases (metabolism)
• Adiponectin (genetics, metabolism)
• Adipose Tissue (cytology, metabolism)
• Animals
• Chemokine CCL2 (genetics, metabolism)
• Diet
• Dietary Fats (metabolism)
• Docosahexaenoic Acids (metabolism)
• Eicosapentaenoic Acid (analogs & derivatives, metabolism)
• Fatty Acids, Omega-3 (chemistry, metabolism, therapeutic use)
• Fatty Liver (diet therapy, metabolism, pathology)
• Glucose Transporter Type 4 (genetics, metabolism)
• Hypoglycemic Agents (metabolism)
• Insulin Receptor Substrate Proteins (genetics, metabolism)
• Insulin Resistance
• Male
• Mice
• Mice, Obese
• Muscle, Skeletal (metabolism)
• Obesity (metabolism, pathology)
• PPAR gamma (genetics, metabolism)
• Resistin (genetics, metabolism)
• Rosiglitazone
• Thiazolidinediones (metabolism)