Omega-3 fatty acids protect from diet-induced obesity, glucose intolerance, and adipose tissue inflammation through PPAR gamma-dependent and PPAR gamma-independent actions

Scope: We tested herein the hypothesis that peroxisome proliferator activated receptor gamma (PPAR) is a major mediator of omega-3 (n-3) protective actions against high-fat diet (HFD) induced obesity, glucose intolerance, and adipose tissue inflammation. Methods and results: C57BL6 wild-type and fat-1 transgenic (fat-1) mice were fed a low-fat diet (LFD) or HFD, treated or not with PPAR gamma antagonist, and evaluated for energy balance, adiposity, glucose tolerance, and adipose tissue inflammation. Fat-1 mice were protected from obesity, fasting hyperglycemia, glucose intolerance, and adipose tissue inflammation. PPAR gamma inhibition completely abolished fat-1 protection against HFD-induced glucose intolerance, but not obesity or adipose tissue inflammation. To investigate the role of myeloid cell as mediator of n-3 beneficialmetabolic actions, mice with deletion (LyzM-PPAR gamma(KO)) or nondeletion (LyzM-PPAR gamma(WT)) of PPAR gamma in myeloid cells were fed either LFD or HFD (lard) or an HFD rich in n-3 (fish oil). Our findings indicate that myeloid cell associated PPAR gamma is not involved in the attenuation of HFD-induced glucose intolerance and adipose tissue inflammation induced by n-3. Conclusion: High endogenous n-3 fatty acid levels protect from HFD obesity, glucose intolerance, and adipose tissue inflammation. Among these, only protection against glucose intolerance is mediated by non-myeloid cell PPAR gamma. (AU)