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Diet‐induced obesity and insulin resistance are associated with brown fat degeneration in SIRT 1‐deficient mice
Author(s) -
Xu Fen,
Zheng Xiaobin,
Lin Beisi,
Liang Hua,
Cai Mengyin,
Cao Huanyi,
Ye Jianping,
Weng Jianping
Publication year - 2016
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21393
Subject(s) - insulin resistance , endocrinology , medicine , adipose tissue , thermogenesis , brown adipose tissue , obesity , insulin , white adipose tissue , biology , inflammation
Objective Recent studies have revealed that SIRT1 gain‐of‐function could promote adipose tissue browning for the adaptive thermogenesis under normal diet. This study investigated the role of SIRT1 loss‐of‐function in diet‐induced obesity and insulin resistance and the mechanism involved in adipose tissue thermogenesis. Methods Male SIRT1 +/− and wild‐type (WT) mice were fed with a high‐fat diet (HFD) for 16 weeks to induce obesity and insulin resistance, while mice on a chow diet were used as lean controls. The phenotype data were collected, and different adipose tissue depots were used for mechanism research. Results Compared with WT mice, SIRT1 +/− mice exhibited increased adiposity and more severe insulin resistance with less thermogenesis under HFD challenge. Strikingly, SIRT1 +/− mice displayed an exacerbated brown adipose tissue (BAT) degeneration phenotype, which was characterized by lower thermogenic activity, aggravated mitochondrial dysfunction, and more mitochondrial loss. In addition, SIRT1 +/− mice showed aggravated inflammation and dysfunction in epididymal adipose tissue after HFD intervention, which also contributed to the systemic insulin resistance. Conclusions Diet‐induced obesity and insulin resistance are associated with BAT degeneration in SIRT1‐deficient mice, which further underlined the beneficial role of SIRT1 in obesity‐associated metabolic disorders.