title: Adiponectin Enhances Cold-Induced Browning of Subcutaneous Adipose Tissue via Promoting M2 Macrophage Proliferation.
abstract: Adiponectin is an abundant adipokine with pleiotropic protective effects against a cluster of obesity-related cardiometabolic disorders. However, its role in adaptive thermogenesis has scarcely been explored. Here we showed that chronic cold exposure led to a markedly elevated production of adiponectin in adipocytes of subcutaneous white adipose tissue (scWAT), which in turn bound to M2 macrophages in the stromal vascular fraction. Chronic cold exposure-induced accumulation of M2 macrophages, activation of beige cells, and thermogenic program were markedly impaired in scWAT of adiponectin knockout (ADN KO) mice, whereas these impairments were reversed by replenishment with adiponectin. Mechanistically, adiponectin was recruited to the cell surface of M2 macrophages via its binding partner T-cadherin and promoted the cell proliferation by activation of Akt, consequently leading to beige cell activation. These findings uncover adiponectin as a key efferent signal for cold-induced adaptive thermogenesis by mediating the crosstalk between adipocytes and M2 macrophages in scWAT.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong 999077, China; Department of Medicine, The University of Hong Kong, Hong Kong 999077, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Hui
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong 999077, China; Department of Medicine, The University of Hong Kong, Hong Kong 999077, China; Department of Endocrinology, Jinling Hospital/Nanjing General Hospital of Nanjing Military Command, Nanjing University School of Medicine, Nanjing 210093, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong 999077, China; Department of Medicine, The University of Hong Kong, Hong Kong 999077, China.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong 999077, China; Department of Medicine, The University of Hong Kong, Hong Kong 999077, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Pan
authors.affiliation: The Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, 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 999077, China; Department of Medicine, The University of Hong Kong, Hong Kong 999077, China.
authors.forename: Tianshi
authors.initials: T
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong 999077, China; Department of Medicine, The University of Hong Kong, Hong Kong 999077, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong 999077, China; Department of Medicine, The University of Hong Kong, Hong Kong 999077, China; Department of Pharmacy and Pharmacology, The University of Hong Kong, Hong Kong 999077, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong 999077, China; Department of Medicine, The University of Hong Kong, Hong Kong 999077, China.
authors.forename: Karen S L
authors.initials: KS
authors.lastname: Lam
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong 999077, China; Department of Medicine, The University of Hong Kong, Hong Kong 999077, China; Department of Pharmacy and Pharmacology, The University of Hong Kong, Hong Kong 999077, China. Electronic address: amxu@hku.hk.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003080:Cold Temperature; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism*; D022722:Thermogenesis / Q000502:physiology
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D015820:Cadherins; C099972:H-cadherin; D051057:Proto-Oncogene Proteins c-akt