Omega-3 fatty acids protect from diet-induced obesity, glucose intolerance, and adipose tissue inflammation through PPARγ-dependent and PPARγ-independent actions.
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-PPARγ(KO)) or nondeletion (LyzM-PPARγ(WT)) 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.
['Belchior|Thiago|T|', 'Paschoal|Vivian A|VA|', 'Magdalon|Juliana|J|', 'Chimin|Patricia|P|', 'Farias|Talita M|TM|', 'Chaves-Filho|Adriano B|AB|', 'Gorjão|Renata|R|', 'St-Pierre|Philippe|P|', 'Miyamoto|Sayuri|S|', 'Kang|Jing X|JX|', 'Deshaies|Yves|Y|', 'Marette|André|A|', 'Festuccia|William|W|']
D000273:Adipose Tissue D000818:Animals D001786:Blood Glucose D059305:Diet, High-Fat D015525:Fatty Acids, Omega-3 D005951:Glucose Tolerance Test D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D009765:Obesity D047495:PPAR gamma
Adiposity Inflammation Glucose metabolism Omega-3 polyunsaturated fatty acids PPARγ antagonism