Clusterin is involved in mediating the metabolic function of adipose SIRT1

iScience

Yu Wang¹  Alok Mitra²  Aimin Xu²  Daniels Konja²  Jae-Han Jeon²  Yiwei Zhang³  Pengcheng Zhang³  In-Kyu Lee³  Ghader Bashiri³ 

[1] Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China;Department of Pharmacology and Pharmacy, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China;The State Key Laboratory of Pharmaceutical Biotechnology, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China;

关键词: Biological sciences;    Molecular physiology;    Cell biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: SIRT1 is a metabolic sensor regulating energy homeostasis. The present study revealed that mice with selective overexpression of human SIRT1 in adipose tissue (Adipo-SIRT1) were protected from high-fat diet (HFD)-induced metabolic abnormalities. Adipose SIRT1 was enriched at mitochondria-ER contacts (MERCs) to trigger mitohormesis and unfolded protein response (UPRmt), in turn preventing ER stress. As a downstream target of UPRmt, clusterin was significantly upregulated and acted together with SIRT1 to regulate the protein and lipid compositions at MERCs of adipose tissue. In mice lacking clusterin, HFD-induced metabolic abnormalities were significantly enhanced and could not be prevented by overexpression of SIRT1 in adipose tissue. Treatment with ER stress inhibitors restored adipose SIRT1-mediated beneficial effects on systemic energy metabolism. In summary, adipose SIRT1 facilitated the dynamic interactions and communications between mitochondria and ER, via MERCs, in turn triggering a mild mitochondrial stress to instigate the defense responses against dietary obesity-induced metabolic dysfunctions.

【 授权许可】

Unknown