title: Local proliferation initiates macrophage accumulation in adipose tissue during obesity.
abstract: Obesity-associated chronic inflammation is characterized by an accumulation of adipose tissue macrophages (ATMs). It is generally believed that those macrophages are derived from peripheral blood monocytes. However, recent studies suggest that local proliferation of macrophages is responsible for ATM accumulation. In the present study, we revealed that both migration and proliferation contribute to ATM accumulation during obesity development. We show that there is a significant increase in ATMs at the early stage of obesity, which is largely due to an enhanced in situ macrophage proliferation. This result was obtained by employing fat-shielded irradiation and bone marrow reconstitution. Additionally, the production of CCL2, a pivotal chemoattractant of monocytes, was not found to be increased at this stage, corroborating with a critical role of proliferation. Nonetheless, as obesity proceeds, the role of monocyte migration into adipose tissue becomes more significant and those new immigrants further proliferate locally. These proliferating ATMs mainly reside in crown-like structures formed by macrophages surrounding dead adipocytes. We further showed that IL-4/STAT6 is a driving force for ATM proliferation. Therefore, we demonstrated that local proliferation of resident macrophages contributes to ATM accumulation during obesity development and has a key role in obesity-associated inflammation.
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, China.
authors.forename: C
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, China.
authors.forename: Q
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, China.
authors.forename: J
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, China.|Biochemistry IDI-IRCCS Laboratory, Department of Experimental Medicine and Surgery, University of Rom 'Tor Vergata', Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Xie
authors.affiliation: School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
authors.forename: K
authors.initials: K
authors.lastname: Liu
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, China.
authors.forename: P
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, China.
authors.forename: F
authors.initials: F
authors.lastname: Qian
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, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
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, China.|The First Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou, China.|Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000032:analysis / Q000097:blood; D059305:Diet, High-Fat; D005434:Flow Cytometry; D005720:Gamma Rays; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018932:Chemokine CCL2; D019394:Ki-67 Antigen; D054411:Receptors, Leptin; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C515447:leptin receptor, mouse; D015847:Interleukin-4