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Adipocyte and Cell Biology

MRP14 enhances the ability of macrophage to recruit T cells and promotes obesity-induced insulin resistance

International Journal of Obesity volume 43, pages 2434–2447 (2019)Cite this article

Subjects

Abstract

Objective

Myeloid-related protein-14 (MRP14) and its binding partner MRP8 play an essential role in innate immune function and have been implicated in a variety of inflammatory diseases. However, the role of MRP14 in obesity-induced inflammation and insulin resistance is not well defined. This study investigated the role of MRP14 in macrophage-mediated adipose tissue inflammation and obesity-induced insulin resistance.

Subjects and results

Wild-type (WT) and Mrp14−/− mice were fed with a high-fat diet or normal chow for 12 weeks. Tissue-resident macrophages in both adipose tissue and liver from obese WT mice expressed higher levels of MRP14 in the visceral adipose fat and liver compared with the lean mice. Mrp14−/− mice demonstrated a significantly improved postprandial insulin sensitivity, as measured by intraperitoneal glucose tolerance test and insulin tolerance testing. Macrophages secreted MRP14 in response to inflammatory stimuli, such as LPS. Extracellular MRP8/14 induced the production of CCL5 and CXCL9. Deficiency of MRP14 did not affect macrophage proliferation, mitochondrial respiration, and glycolytic function, but Mrp14−/− macrophages showed a reduced ability to attract T cells. Depletion of the extracellular MRP14 reduced the T cell attracting ability of WT macrophages to a level similar to Mrp14−/− macrophages.

Conclusion

Our data indicate that MRP14 deficiency decreases obesity-induced insulin resistance and MRP8/14 regulates T-cell recruitment through the induction of T-cell chemoattractant production from macrophages.

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Funding

This work was supported by grants from National Institutes of Health (K01DK105108 and K99ES026241), National Natural Science Foundation of China (81670431, 31870906, 81370942, Y2110580, and 81101247), National Science and Technology Major Project (2016YFC1305803), American Heart Association (17GRNT33670485), American Association of Immunologists (CIIF-8745), and Hubei Regenerative Medicine Research Center.

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Authors and Affiliations

  1. College of Health Science & Nursing, Wuhan Polytechnic University, 430023, Wuhan, Hubei, China

    Chang Xia

  2. Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, 44106, USA

    Chang Xia, Michael Razavi, Yunmei Wang, Daniel I. Simon, Sanjay Rajagopalan & Jixin Zhong

  3. Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR, 97239, USA

    Xiaoquan Rao

  4. Department of Internal Medicine, The Ohio State University, Columbus, OH, 43210, USA

    Zachary Braunstein & Shi Zhao

  5. Department of Endocrinology, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430014, Wuhan, Hubei, China

    Hong Mao

  6. Department of Health Sciences, University of Missouri, Columbia, MO, USA

    Amelia C. Toomey

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  1. Chang Xia
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Contributions

CX and JZ researched data and wrote the paper. XR and ZB researched data. MR, ZB, SZ, DIS, SR, HM, ACT, and XR contributed to discussion. JZ, ZB, MR, ACT, and SZ reviewed and edited the paper. JZ is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Shi Zhao or Jixin Zhong.

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Xia, C., Razavi, M., Rao, X. et al. MRP14 enhances the ability of macrophage to recruit T cells and promotes obesity-induced insulin resistance. Int J Obes 43, 2434–2447 (2019). https://doi.org/10.1038/s41366-019-0366-4

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