title: Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation.
abstract: Adipose tissue (AT) of obese mice and humans accumulates immune cells, which secrete cytokines that can promote insulin resistance. AT macrophages (ATMs) are thought to originate from bone-marrow-derived monocytes, which infiltrate the tissue from the circulation. Here, we show that a major fraction of macrophages unexpectedly undergo cell division locally within AT, as detected by Ki67 expression and 5-ethynyl-2'-deoxyuridine incorporation. Macrophages within the visceral AT (VAT), but not those in other tissues (including liver and spleen), displayed increased proliferation in obesity. Importantly, depletion of blood monocytes had no impact on ATM content, whereas their proliferation in situ continued. Treatment with monocyte chemotactic protein 1 (MCP-1) induced macrophage cell division in AT explants, whereas mcp-1 deficiency in vivo decreased ATM proliferation. These results reveal that, in addition to blood monocyte recruitment, in situ proliferation driven by MCP-1 is an important process by which macrophages accumulate in the VAT in obesity.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Shinya U
authors.initials: SU
authors.lastname: Amano
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Cohen
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Pranitha
authors.initials: P
authors.lastname: Vangala
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Michaela
authors.initials: M
authors.lastname: Tencerova
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Nicoloro
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Yawe
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Czech
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Aouadi
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002455:Cell Division; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D019394:Ki-67 Antigen