Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal Ccl2/Ccr2-Dependent Manner

doi:10.1016/j.cmet.2016.07.009

. 2016 Aug 9;24(2):295-310.

doi: 10.1016/j.cmet.2016.07.009.

Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal Ccl2/Ccr2-Dependent Manner

Affiliations

¹ Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
² Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan. Electronic address: jnakae5330@a7.keio.jp.
³ Department of Human Genetics, National Center for Child Health and Development, Tokyo 157-0074, Japan.
⁴ Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
⁵ Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Department of Endocrinology and Metabolism, Chibune General Hospital, Osaka 555-0011, Japan.
⁶ Animal Resource Development Unit, Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan; Genetic Engineering Team, Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan.
⁷ Genetic Engineering Team, Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan.

PMID: 27508875
DOI: 10.1016/j.cmet.2016.07.009

Free article

Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal Ccl2/Ccr2-Dependent Manner

Yoshinaga Kawano et al. Cell Metab. 2016.

Free article

. 2016 Aug 9;24(2):295-310.

doi: 10.1016/j.cmet.2016.07.009.

Authors

Affiliations

¹ Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
² Division of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan. Electronic address: jnakae5330@a7.keio.jp.
³ Department of Human Genetics, National Center for Child Health and Development, Tokyo 157-0074, Japan.
⁴ Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
⁵ Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Department of Endocrinology and Metabolism, Chibune General Hospital, Osaka 555-0011, Japan.
⁶ Animal Resource Development Unit, Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan; Genetic Engineering Team, Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan.
⁷ Genetic Engineering Team, Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan.

PMID: 27508875
DOI: 10.1016/j.cmet.2016.07.009

Abstract

High-fat diet (HFD) induces low-grade chronic inflammation and insulin resistance. However, little is known about the mechanism underlying HFD-induced chronic inflammation in peripheral insulin-responsive tissues. Here, we show that colonic pro-inflammatory macrophages regulate insulin sensitivity under HFD conditions. To investigate the pathophysiological role of colonic macrophages, we generated macrophage-specific chemokine (C-C Motif) receptor 2 (Ccr2) knockout (M-Ccr2KO) and intestinal epithelial cell-specific tamoxifen-inducible Ccl2 knockout (Vil-Ccl2KO) mice. Both strains exhibited similar body weight to control under HFD. However, they exhibited decreased infiltration of colonic pro-inflammatory macrophages, decreased intestinal permeability, and inactivation of the colonic inflammasome. Interestingly, they showed significantly improved glucose tolerance and insulin sensitivity with decreased chronic inflammation of adipose tissue. Therefore, inhibition of pro-inflammatory macrophage infiltration prevents HFD-induced insulin resistance and could be a novel therapeutic approach for type 2 diabetes.

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Comment in

Colonic Macrophages "Remote Control" Adipose Tissue Inflammation and Insulin Resistance.
Biswas SK, Bonecchi R. Biswas SK, et al. Cell Metab. 2016 Aug 9;24(2):196-8. doi: 10.1016/j.cmet.2016.07.020. Cell Metab. 2016. PMID: 27508866

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Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal Ccl2/Ccr2-Dependent Manner

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Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal Ccl2/Ccr2-Dependent Manner

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