CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages

Chunxing Zheng, Qian Yang, Chunliang Xu, Peishun Shou, Jianchang Cao, Menghui Jiang, Qing Chen, Gang Cao, Yanyan Han, Fengying Li, Wei Cao, Liying Zhang, Li Zhang, Yufang Shi, Ying Wang

Research output: Contribution to journalArticle

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Abstract

Obesity-associated inflammation is accompanied by the accumulation of adipose tissue macrophages (ATMs), which is believed to predispose obese individuals to insulin resistance. CD11b (integrin αM) is highly expressed on monocytes and macrophages and is critical for their migration and function. We found here that high-fat diet-induced insulin resistance was significantly reduced in CD11bdeficient mice. Interestingly, the recruitment of monocytes to adipose tissue is impaired when CD11b is deficient, although the cellularity of ATMs in CD11b-deficient mice is higher than that in wild-type mice. We further found that the increase in ATMs is caused mainly by their vigorous proliferation in the absence of CD11b. Moreover, the proliferation and alternative activation of ATMs are regulated by the IL-4/STAT6 axis, which is inhibited by CD11b through the activity of phosphatase SHP-1. Thus, CD11b plays a critical role in obesity-induced insulin resistance by limiting the proliferation and alternative activation of ATMs.

Original languageEnglish (US)
Pages (from-to)E7239-E7248
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number52
DOIs
StatePublished - Dec 29 2015
Externally publishedYes

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Insulin Resistance
Adipose Tissue
Obesity
Macrophages
Monocytes
Non-Receptor Type 6 Protein Tyrosine Phosphatase
High Fat Diet
Integrins
Interleukin-4
Inflammation

Keywords

  • Alternative activation
  • Insulin resistance
  • Integrin CD11b
  • Macrophage proliferation
  • Obesity

ASJC Scopus subject areas

  • General

Cite this

CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages. / Zheng, Chunxing; Yang, Qian; Xu, Chunliang; Shou, Peishun; Cao, Jianchang; Jiang, Menghui; Chen, Qing; Cao, Gang; Han, Yanyan; Li, Fengying; Cao, Wei; Zhang, Liying; Zhang, Li; Shi, Yufang; Wang, Ying.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 52, 29.12.2015, p. E7239-E7248.

Research output: Contribution to journalArticle

Zheng, Chunxing ; Yang, Qian ; Xu, Chunliang ; Shou, Peishun ; Cao, Jianchang ; Jiang, Menghui ; Chen, Qing ; Cao, Gang ; Han, Yanyan ; Li, Fengying ; Cao, Wei ; Zhang, Liying ; Zhang, Li ; Shi, Yufang ; Wang, Ying. / CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 52. pp. E7239-E7248.
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AU - Xu, Chunliang

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AU - Cao, Jianchang

AU - Jiang, Menghui

AU - Chen, Qing

AU - Cao, Gang

AU - Han, Yanyan

AU - Li, Fengying

AU - Cao, Wei

AU - Zhang, Liying

AU - Zhang, Li

AU - Shi, Yufang

AU - Wang, Ying

PY - 2015/12/29

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N2 - Obesity-associated inflammation is accompanied by the accumulation of adipose tissue macrophages (ATMs), which is believed to predispose obese individuals to insulin resistance. CD11b (integrin αM) is highly expressed on monocytes and macrophages and is critical for their migration and function. We found here that high-fat diet-induced insulin resistance was significantly reduced in CD11bdeficient mice. Interestingly, the recruitment of monocytes to adipose tissue is impaired when CD11b is deficient, although the cellularity of ATMs in CD11b-deficient mice is higher than that in wild-type mice. We further found that the increase in ATMs is caused mainly by their vigorous proliferation in the absence of CD11b. Moreover, the proliferation and alternative activation of ATMs are regulated by the IL-4/STAT6 axis, which is inhibited by CD11b through the activity of phosphatase SHP-1. Thus, CD11b plays a critical role in obesity-induced insulin resistance by limiting the proliferation and alternative activation of ATMs.

AB - Obesity-associated inflammation is accompanied by the accumulation of adipose tissue macrophages (ATMs), which is believed to predispose obese individuals to insulin resistance. CD11b (integrin αM) is highly expressed on monocytes and macrophages and is critical for their migration and function. We found here that high-fat diet-induced insulin resistance was significantly reduced in CD11bdeficient mice. Interestingly, the recruitment of monocytes to adipose tissue is impaired when CD11b is deficient, although the cellularity of ATMs in CD11b-deficient mice is higher than that in wild-type mice. We further found that the increase in ATMs is caused mainly by their vigorous proliferation in the absence of CD11b. Moreover, the proliferation and alternative activation of ATMs are regulated by the IL-4/STAT6 axis, which is inhibited by CD11b through the activity of phosphatase SHP-1. Thus, CD11b plays a critical role in obesity-induced insulin resistance by limiting the proliferation and alternative activation of ATMs.

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KW - Macrophage proliferation

KW - Obesity

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