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Adipocyte SIRT 1 controls systemic insulin sensitivity by modulating macrophages in adipose tissue
Author(s) -
Hui Xiaoyan,
Zhang Mingliang,
Gu Ping,
Li Kuai,
Gao Yuan,
Wu Donghai,
Wang Yu,
Xu Aimin
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201643184
Subject(s) - adipose tissue , adipocyte , medicine , endocrinology , adipose tissue macrophages , insulin resistance , nfat , biology , inflammation , adipokine , macrophage polarization , adiponectin , microbiology and biotechnology , white adipose tissue , transcription factor , insulin , phenotype , immunology , biochemistry , gene
Adipose tissue inflammation, characterized by augmented infiltration and altered polarization of macrophages, contributes to insulin resistance and its associated metabolic diseases. The NAD + ‐dependent deacetylase SIRT 1 serves as a guardian against metabolic disorders in multiple tissues. To dissect the roles of SIRT 1 in adipose tissues, metabolic phenotypes of mice with selective ablation of SIRT 1 in adipocytes and myeloid cells were monitored. Compared to myeloid‐specific SIRT 1 depletion, mice with adipocyte‐selective deletion of SIRT 1 are more susceptible to diet‐induced insulin resistance. The phenotypic changes in adipocyte‐selective SIRT 1 knockout mice are associated with an increased number of adipose‐resident macrophages and their polarization toward the pro‐inflammatory M1 subtype. Mechanistically, SIRT 1 in adipocytes modulates expression and secretion of several adipokines, including adiponectin, MCP ‐1, and interleukin 4, which in turn alters recruitment and polarization of the macrophages in adipose tissues. In adipocytes, SIRT 1 deacetylates the transcription factor NFAT c1 and thereby enhances the binding of NFAT c1 to the Il4 gene promoter. These findings suggest that adipocyte SIRT 1 controls systemic glucose homeostasis and insulin sensitivity via the cross talk with adipose‐resident macrophages.