title: Diet-induced obesity and insulin resistance are associated with brown fat degeneration in SIRT1-deficient mice.
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.
authors.affiliation: Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China.
authors.forename: Beisi
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China.
authors.forename: Mengyin
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China.
authors.forename: Huanyi
authors.initials: H
authors.lastname: Cao
authors.affiliation: Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.|Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Weng
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D009765:Obesity / Q000378:metabolism*; D056565:Sirtuin 2 / Q000378:metabolism*; D022722:Thermogenesis
chemical_list: D056565:Sirtuin 2