iScience | |
Clusterin is involved in mediating the metabolic function of adipose SIRT1 | |
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