Clusterin is involved in mediating the metabolic function of adipose SIRT1.

ABSTRACT: 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 (UPR^mt), in turn preventing ER stress. As a downstream target of UPR^mt, 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 inhibitor

SUBMITTER: Zhang P 

PROVIDER: S-EPMC8762396 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature