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Nat Commun. 2017 Aug 18;8(1):286. doi: 10.1038/s41467-017-00231-1.

CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors.

Author information

1
First Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
2
Department of Nutrition, Faculty of Medicine, University of Hasanuddin, Makassar, Kota Makassar, Sulawesi Selatan, 90245, Indonesia.
3
Department of Pathology, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
4
Department of Diagnostic Pathology, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
5
Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
6
Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
7
Department of Immune Regulation, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, 272-8516, Japan.
8
Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
9
JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.
10
Toyama Prefectural Institute for Pharmaceutical Research, 17-1 Nakataikouyama, Imiz-shi, Toyama, 939-0363, Japan.
11
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
12
Department of Molecular Diabetic Medicine, Diabetes Research Center, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan.
13
Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
14
Section of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan.
15
Doctoral Program in Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8574, Japan.
16
Department of Molecular Metabolic Regulation, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
17
Department of Molecular Neuroscience, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
18
Department of Metabolism and Nutrition, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.
19
Department of Disease Control, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
20
First Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan. shihof@med.u-toyama.ac.jp.
21
First Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan. tobe@med.u-toyama.ac.jp.

Abstract

Adipose tissue resident macrophages have important roles in the maintenance of tissue homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or anti-inflammatory cytokines. Here, we show that M2-like macrophages in adipose tissue regulate systemic glucose homeostasis by inhibiting adipocyte progenitor proliferation via the CD206/TGFβ signaling pathway. We show that adipose tissue CD206+ cells are primarily M2-like macrophages, and ablation of CD206+ M2-like macrophages improves systemic insulin sensitivity, which was associated with an increased number of smaller adipocytes. Mice genetically engineered to have reduced numbers of CD206+ M2-like macrophages show a down-regulation of TGFβ signaling in adipose tissue, together with up-regulated proliferation and differentiation of adipocyte progenitors. Our findings indicate that CD206+ M2-like macrophages in adipose tissues create a microenvironment that inhibits growth and differentiation of adipocyte progenitors and, thereby, control adiposity and systemic insulin sensitivity.Adipose tissue contains macrophages that can influence both local and systemic metabolism via the secretion of cytokines. Here, Nawaz et al. report that M2-like macrophages, present in adipose tissue, create a microenvironment that inhibits proliferation of adipocyte progenitors due to the secretion of TGF-β1.

PMID:
28819169
PMCID:
PMC5561263
DOI:
10.1038/s41467-017-00231-1
[Indexed for MEDLINE]
Free PMC Article

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