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Lipoatrophy‐associated insulin resistance and hepatic steatosis are attenuated by intake of diet rich in omega 3 fatty acids.
Author(s) -
Festuccia William T.,
Moustaid-Moussa Naima,
Moreira Rafael
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05121
Subject(s) - medicine , lipogenesis , steatosis , endocrinology , nonalcoholic fatty liver disease , glucose homeostasis , insulin resistance , fatty liver , biology , polyunsaturated fatty acid , lipid metabolism , insulin , fatty acid , biochemistry , disease
We evaluated in this study glucose homeostasis and progression of nonalcoholic fatty liver disease (NAFLD) and hepatomegaly in severe lipoatrophic mice and their modulation by intake of a diet rich in omega 3 (n‐3) fatty acids. Severe lipoatrophic mice induced by adipocyte‐specific PPARγ deletion (A‐PPARγ KO) and littermate controls (A‐PPARγ WT) were evaluated for glucose homeostasis and liver mass, proteomics, lipidomics, inflammation and fibrosis after intake of a chow diet. Lipoatrophic mice were heavier than controls due to increased food intake and energy efficiency, severely glucose intolerant and hyperinsulinemic, and developed NAFLD characterized by increased liver glycogen, triacylglycerol and diacylglycerol contents, DNA and mitotic index, apoptosis, inflammation, steatosis score and fibrosis. This was associated with activation of de novo lipogenesis and liver enrichment with monounsaturated in detriment of polyunsaturated fatty acids including n‐3 fatty acids. Administration of a high‐fat diet rich in n‐3 fatty acids (HFO) inhibited de novo lipogenesis, enriched liver with n‐3 fatty acids, reduced hepatic steatosis, apoptosis, inflammation and steatosis and improved glucose homeostasis in lipoatrophic mice. In conclusion, diet enrichment with n‐3 fatty acids is an effective strategy to improve glucose homeostasis and reduce liver steatosis and inflammation without affecting hepatomegaly in severe lipoatrophic mice. Support or Funding Information Funded by FAPESP (2015/19530‐5).