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

Allah Nawaz; Aminuddin Aminuddin; Tomonobu Kado; Akiko Takikawa; Seiji Yamamoto; Koichi Tsuneyama; Yoshiko Igarashi; Masashi Ikutani; Yasuhiro Nishida; Yoshinori Nagai; Kiyoshi Takatsu; Johji Imura; Masakiyo Sasahara; Yukiko Okazaki; Kohjiro Ueki; Tadashi Okamura; Kumpei Tokuyama; Akira Ando; Michihiro Matsumoto; Hisashi Mori; Takashi Nakagawa; Norihiko Kobayashi; Kumiko Saeki; Isao Usui; Shiho Fujisaka; Kazuyuki Tobe

doi:10.1038/s41467-017-00231-1

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

Allah Nawaz, Aminuddin Aminuddin, Tomonobu Kado, Akiko Takikawa, Seiji Yamamoto, Koichi Tsuneyama, Yoshiko Igarashi, Masashi Ikutani, Yasuhiro Nishida, Yoshinori Nagai, Kiyoshi Takatsu, Johji Imura, Masakiyo Sasahara, Yukiko Okazaki, Kohjiro Ueki, Tadashi Okamura, Kumpei Tokuyama, Akira Ando, Michihiro Matsumoto, Hisashi MoriTakashi Nakagawa, Norihiko Kobayashi, Kumiko Saeki, Isao Usui, Shiho Fujisaka^*, Kazuyuki Tobe

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

196 Scopus citations

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.

Original language	English
Article number	286
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00231-1
State	Published - 2017/12/01

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-017-00231-1

Cite this

Nawaz, A., Aminuddin, A., Kado, T., Takikawa, A., Yamamoto, S., Tsuneyama, K., Igarashi, Y., Ikutani, M., Nishida, Y., Nagai, Y., Takatsu, K., Imura, J., Sasahara, M., Okazaki, Y., Ueki, K., Okamura, T., Tokuyama, K., Ando, A., Matsumoto, M., ... Tobe, K. (2017). CD206⁺ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors. Nature Communications, 8(1), Article 286. https://doi.org/10.1038/s41467-017-00231-1

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title = "CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors",

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.",

author = "Allah Nawaz and Aminuddin Aminuddin and Tomonobu Kado and Akiko Takikawa and Seiji Yamamoto and Koichi Tsuneyama and Yoshiko Igarashi and Masashi Ikutani and Yasuhiro Nishida and Yoshinori Nagai and Kiyoshi Takatsu and Johji Imura and Masakiyo Sasahara and Yukiko Okazaki and Kohjiro Ueki and Tadashi Okamura and Kumpei Tokuyama and Akira Ando and Michihiro Matsumoto and Hisashi Mori and Takashi Nakagawa and Norihiko Kobayashi and Kumiko Saeki and Isao Usui and Shiho Fujisaka and Kazuyuki Tobe",

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doi = "10.1038/s41467-017-00231-1",

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Nawaz, A, Aminuddin, A, Kado, T , Takikawa, A , Yamamoto, S, Tsuneyama, K, Igarashi, Y, Ikutani, M, Nishida, Y, Nagai, Y, Takatsu, K, Imura, J, Sasahara, M, Okazaki, Y, Ueki, K, Okamura, T, Tokuyama, K, Ando, A, Matsumoto, M, Mori, H , Nakagawa, T, Kobayashi, N, Saeki, K, Usui, I, Fujisaka, S & Tobe, K 2017, 'CD206⁺ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors', Nature Communications, vol. 8, no. 1, 286. https://doi.org/10.1038/s41467-017-00231-1

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T1 - CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors

AU - Nawaz, Allah

AU - Aminuddin, Aminuddin

AU - Kado, Tomonobu

AU - Takikawa, Akiko

AU - Yamamoto, Seiji

AU - Tsuneyama, Koichi

AU - Igarashi, Yoshiko

AU - Ikutani, Masashi

AU - Nishida, Yasuhiro

AU - Nagai, Yoshinori

AU - Takatsu, Kiyoshi

AU - Imura, Johji

AU - Sasahara, Masakiyo

AU - Okazaki, Yukiko

AU - Ueki, Kohjiro

AU - Okamura, Tadashi

AU - Tokuyama, Kumpei

AU - Ando, Akira

AU - Matsumoto, Michihiro

AU - Mori, Hisashi

AU - Nakagawa, Takashi

AU - Kobayashi, Norihiko

AU - Saeki, Kumiko

AU - Usui, Isao

AU - Fujisaka, Shiho

AU - Tobe, Kazuyuki

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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AN - SCOPUS:85027855813

SN - 2041-1723

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