title: CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages.
abstract: Obesity-associated inflammation is accompanied by the accumulation of adipose tissue macrophages (ATMs), which is believed to predispose obese individuals to insulin resistance. CD11b (integrin αM) is highly expressed on monocytes and macrophages and is critical for their migration and function. We found here that high-fat diet-induced insulin resistance was significantly reduced in CD11b-deficient mice. Interestingly, the recruitment of monocytes to adipose tissue is impaired when CD11b is deficient, although the cellularity of ATMs in CD11b-deficient mice is higher than that in wild-type mice. We further found that the increase in ATMs is caused mainly by their vigorous proliferation in the absence of CD11b. Moreover, the proliferation and alternative activation of ATMs are regulated by the IL-4/STAT6 axis, which is inhibited by CD11b through the activity of phosphatase SHP-1. Thus, CD11b plays a critical role in obesity-induced insulin resistance by limiting the proliferation and alternative activation of ATMs.
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Chunxing
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Chunliang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Peishun
authors.identifier: http://orcid.org/0000-0001-7685-7471
authors.initials: P
authors.lastname: Shou
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Jianchang
authors.initials: J
authors.lastname: Cao
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Menghui
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Gang
authors.initials: G
authors.lastname: Cao
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Fengying
authors.initials: F
authors.lastname: Li
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China;
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: The First Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou 215006, China;
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Vascular and Inflammatory Diseases, Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China; The First Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou 215006, China; Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ 08901 yufangshi@sibs.ac.cn yingwang@sibs.ac.cn.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China; yufangshi@sibs.ac.cn yingwang@sibs.ac.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D039481:CD11b Antigen / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D005434:Flow Cytometry; D015870:Gene Expression; D015151:Immunoblotting; D007333:Insulin Resistance / Q000235:genetics*; D015847:Interleukin-4 / Q000378:metabolism; D008262:Macrophage Activation / Q000235:genetics; D008264:Macrophages / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse
keywords: alternative activation; insulin resistance; integrin CD11b; macrophage proliferation; obesity