title: Adipocyte SIRT1 controls systemic insulin sensitivity by modulating macrophages in adipose tissue.
abstract: 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 SIRT1 serves as a guardian against metabolic disorders in multiple tissues. To dissect the roles of SIRT1 in adipose tissues, metabolic phenotypes of mice with selective ablation of SIRT1 in adipocytes and myeloid cells were monitored. Compared to myeloid-specific SIRT1 depletion, mice with adipocyte-selective deletion of SIRT1 are more susceptible to diet-induced insulin resistance. The phenotypic changes in adipocyte-selective SIRT1 knockout mice are associated with an increased number of adipose-resident macrophages and their polarization toward the pro-inflammatory M1 subtype. Mechanistically, SIRT1 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, SIRT1 deacetylates the transcription factor NFATc1 and thereby enhances the binding of NFATc1 to theIl4gene promoter. These findings suggest that adipocyte SIRT1 controls systemic glucose homeostasis and insulin sensitivity via the cross talk with adipose-resident macrophages.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.|Department of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Xiaoyan
authors.identifier: 0000-0002-7525-5812
authors.initials: X
authors.lastname: Hui
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.|Department of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Endocrinology, School of Medicine, Nanjing University Nanjing General Hospital of Nanjing Military Command, Nanjing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gu
authors.affiliation: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.|CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
authors.forename: Kuai
authors.initials: K
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.|Department of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.|CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China yuwanghk@hku.hk amxu@hku.hk.|Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.
authors.forename: Yu
authors.identifier: 0000-0001-8697-2940
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China yuwanghk@hku.hk amxu@hku.hk.|Department of Medicine, The University of Hong Kong, Hong Kong, China.|Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.
authors.forename: Aimin
authors.identifier: 0000-0002-0668-033X
authors.initials: A
authors.lastname: Xu
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000818:Animals; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D059305:Diet, High-Fat; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D051057:Proto-Oncogene Proteins c-akt; D056564:Sirtuin 1; D005947:Glucose
keywords: SIRT1; insulin resistance; macrophage infiltration and polarization; metabolic inflammation; obesity