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标题：Clusterin is involved in mediating the metabolic function of adipose SIRT1
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作者：Pengcheng Zhang ; Daniels Konja ; Yiwei Zhang 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：1
页码：1-26
DOI：10.1016/j.isci.2021.103709
语种：English
出版社：Elsevier
摘要：SummarySIRT1 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.Graphical abstractDisplay OmittedHighlights•Adipose SIRT1 triggers mitohormesis and UPRmt, in turn upregulating clusterin•Adipose SIRT1 and clusterin regulate the protein and lipid compositions at MERCs•Adipose SIRT1 and clusterin reinforce UPRmt-mediated anti-ER stress signaling•Adipose SIRT1 dysfunction causes obesity and associated metabolic abnormalitiesBiological sciences; Molecular physiology; Cell biology