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Inhibition of Mitochondrial Calcium Overload by SIRT3 Prevents Obesity- or Age-Related Whitening of Brown Adipose Tissue.
Gao, Peng; Jiang, Yanli; Wu, Hao; Sun, Fang; Li, Yaohong; He, Hongbo; Wang, Bin; Lu, Zongshi; Hu, Yingru; Wei, Xiao; Cui, Yuanting; He, Chengkang; Wang, Lijuan; Zheng, Hongting; Yang, Gangyi; Liu, Daoyan; Yan, Zhencheng; Zhu, Zhiming.
Affiliation
  • Gao P; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Jiang Y; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Wu H; Department of Endocrinology, Menghai People's Hospital, Xishuangbanna, Yunnan, China.
  • Sun F; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Li Y; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • He H; Department of Endocrinology, Menghai People's Hospital, Xishuangbanna, Yunnan, China.
  • Wang B; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Lu Z; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Hu Y; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Wei X; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Cui Y; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • He C; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Wang L; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Zheng H; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Yang G; Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
  • Liu D; Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, and Chongqing Clinical Research Center for Geriatrics, Chongqing, China.
  • Yan Z; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
  • Zhu Z; Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, and Chongqing Institute of Hypertension, Chongqing, China zhenchengyan@sina.com zhuzm@yahoo.com.
Diabetes ; 69(2): 165-180, 2020 02.
Article in En | MEDLINE | ID: mdl-31712319
ABSTRACT
The whitening and loss of brown adipose tissue (BAT) during obesity and aging promote metabolic disorders and related diseases. The imbalance of Ca2+ homeostasis accounts for the dysfunction and clearance of mitochondria during BAT whitening. Capsaicin, a dietary factor activating TRPV1, can inhibit obesity induced by high-fat diet (HFD), but whether capsaicin inhibits BAT loss and the underlying mechanism remain unclear. In this study, we determined that the inhibitory effects of capsaicin on HFD-induced obesity and BAT whitening were dependent on the participation of SIRT3, a critical mitochondrial deacetylase. SIRT3 also mediated all of the beneficial effects of capsaicin on alleviating reactive oxygen species generation, elevating mitochondrial activity, and restricting mitochondrial calcium overload induced by HFD. Mechanistically, SIRT3 inhibits mitochondrial calcium uniporter (MCU)-mediated mitochondrial calcium overload by reducing the H3K27ac level on the MCU promoter in an AMPK-dependent manner. In addition, HFD also inhibits AMPK activity to reduce SIRT3 expression, which could be reversed by capsaicin. Capsaicin intervention also inhibited aging-induced BAT whitening through this mechanism. In conclusion, this study emphasizes a critical role of the AMPK/SIRT3 pathway in the maintenance of BAT morphology and function and suggests that intervention in this pathway may be an effective target for preventing obesity- or age-related metabolic diseases.
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Full text: 1 Database: MEDLINE Main subject: Aging / Calcium / Sirtuin 3 / Mitochondria / Obesity Limits: Animals Language: En Year: 2020 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Aging / Calcium / Sirtuin 3 / Mitochondria / Obesity Limits: Animals Language: En Year: 2020 Type: Article