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

Chang Xia, Michael Razavi, Xiaoquan Rao, Zachary Braunstein, Hong Mao, Amelia C. Toomey, Yunmei Wang, Daniel I. Simon, Shi Zhao, Sanjay Rajagopalan, Jixin Zhong

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2434-2447
Number of pages14
JournalInternational Journal of Obesity
Volume43
Issue number12
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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    Xia, C., Razavi, M., Rao, X., Braunstein, Z., Mao, H., Toomey, A. C., Wang, Y., Simon, D. I., Zhao, S., Rajagopalan, S., & Zhong, J. (2019). MRP14 enhances the ability of macrophage to recruit T cells and promotes obesity-induced insulin resistance. International Journal of Obesity, 43(12), 2434-2447. https://doi.org/10.1038/s41366-019-0366-4