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. 2016 Mar;24(3):634-42.
doi: 10.1002/oby.21393.

Diet-induced Obesity and Insulin Resistance Are Associated With Brown Fat Degeneration in SIRT1-deficient Mice

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Diet-induced Obesity and Insulin Resistance Are Associated With Brown Fat Degeneration in SIRT1-deficient Mice

Fen Xu et al. Obesity (Silver Spring). .
Free article

Abstract

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.

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