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

• Published in: Molecular nutrition & food research Vol. 59; no. 5; pp. 957 - 967
• Main Authors: Belchior, Thiago, Paschoal, Vivian A, Magdalon, Juliana, Chimin, Patricia, Farias, Talita M, Chaves‐Filho, Adriano B, Gorjão, Renata, St.‐Pierre, Philippe, Miyamoto, Sayuri, Kang, Jing X, Deshaies, Yves, Marette, André, Festuccia, William
• Format: Journal Article
• Language: English
• Published: Germany Wiley-VCH 01-05-2015; Blackwell Publishing Ltd
• Subjects: adipose tissue; Adipose Tissue - pathology; Adiposity; Animals; antagonists; Blood Glucose - analysis; Diet, High-Fat; energy balance; fasting; Fatty Acids, Omega-3 - administration & dosage; fish oils; genetically modified organisms; glucose; Glucose metabolism; glucose tolerance; Glucose Tolerance Test; high fat diet; hyperglycemia; Inflammation; lard; low fat diet; Male; Mice; Mice, Inbred C57BL; obesity; Obesity - prevention & control; omega-3 fatty acids; Omega-3 polyunsaturated fatty acids; PPAR gamma - physiology; PPARγ antagonism; Glucose metabolism; Inflammation; PPARγ antagonism; Adiposity; Omega-3 polyunsaturated fatty acids
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201400914

SCOPE: We tested herein the hypothesis that peroxisome proliferator activated receptor γ (PPARγ) 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 PPARγ 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. PPARγ 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 beneficial metabolic actions, mice with deletion (LyzM‐PPARγᴷᴼ) or nondeletion (LyzM‐PPARγᵂᵀ) of PPARγ 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 PPARγ 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 PPARγ.