PMID- 24374218 OWN - NLM STAT- MEDLINE DCOM- 20140612 LR - 20211021 IS - 1932-7420 (Electronic) IS - 1550-4131 (Print) IS - 1550-4131 (Linking) VI - 19 IP - 1 DP - 2014 Jan 7 TI - Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. PG - 162-171 LID - 10.1016/j.cmet.2013.11.017 [doi] AB - 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. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Amano, Shinya U AU - Amano SU AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. FAU - Cohen, Jessica L AU - Cohen JL AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. FAU - Vangala, Pranitha AU - Vangala P AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. FAU - Tencerova, Michaela AU - Tencerova M AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. FAU - Nicoloro, Sarah M AU - Nicoloro SM AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. FAU - Yawe, Joseph C AU - Yawe JC AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. FAU - Shen, Yuefei AU - Shen Y AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. FAU - Czech, Michael P AU - Czech MP AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. FAU - Aouadi, Myriam AU - Aouadi M AD - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. LA - eng GR - DK085753/DK/NIDDK NIH HHS/United States GR - R01 DK085753/DK/NIDDK NIH HHS/United States GR - F32 DK098879/DK/NIDDK NIH HHS/United States GR - P01 AI046629/AI/NIAID NIH HHS/United States GR - F32DK098879/DK/NIDDK NIH HHS/United States GR - AI046629/AI/NIAID NIH HHS/United States GR - DK325220/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20131226 PL - United States TA - Cell Metab JT - Cell metabolism JID - 101233170 RN - 0 (Biomarkers) RN - 0 (Chemokine CCL2) RN - 0 (Ki-67 Antigen) SB - IM MH - Adipose Tissue/*pathology MH - Animals MH - Biomarkers/metabolism MH - Cell Division MH - Cell Proliferation MH - Chemokine CCL2/metabolism MH - Humans MH - Inflammation/*pathology MH - Ki-67 Antigen/metabolism MH - Macrophages/metabolism/*pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Monocytes/metabolism MH - Obesity/metabolism/*pathology PMC - PMC3931314 MID - NIHMS552740 EDAT- 2014/01/01 06:00 MHDA- 2014/06/13 06:00 PMCR- 2015/01/07 CRDT- 2013/12/31 06:00 PHST- 2012/08/22 00:00 [received] PHST- 2013/06/04 00:00 [revised] PHST- 2013/11/15 00:00 [accepted] PHST- 2013/12/31 06:00 [entrez] PHST- 2014/01/01 06:00 [pubmed] PHST- 2014/06/13 06:00 [medline] PHST- 2015/01/07 00:00 [pmc-release] AID - 10.1016/j.cmet.2013.11.017 [doi] PST - ppublish SO - Cell Metab. 2014 Jan 7;19(1):162-171. doi: 10.1016/j.cmet.2013.11.017. Epub 2013 Dec 26.