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

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)
JournalInternational Journal of Obesity
DOIs
StatePublished - Jan 1 2019

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Insulin Resistance
Obesity
Macrophages
T-Lymphocytes
Proteins
Adipose Tissue
Calgranulin B
Inflammation
Obese Mice
Protein Deficiency
Intra-Abdominal Fat
Liver
Chemotactic Factors
High Fat Diet
Glucose Tolerance Test
Respiration
Insulin

ASJC Scopus subject areas

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

Cite this

MRP14 enhances the ability of macrophage to recruit T cells and promotes obesity-induced insulin resistance. / Xia, Chang; Razavi, Michael; Rao, Xiaoquan; Braunstein, Zachary; Mao, Hong; Toomey, Amelia C.; Wang, Yunmei; Simon, Daniel I.; Zhao, Shi; Rajagopalan, Sanjay; Zhong, Jixin.

In: International Journal of Obesity, 01.01.2019.

Research output: Contribution to journalArticle

Xia, Chang ; Razavi, Michael ; Rao, Xiaoquan ; Braunstein, Zachary ; Mao, Hong ; Toomey, Amelia C. ; Wang, Yunmei ; Simon, Daniel I. ; Zhao, Shi ; Rajagopalan, Sanjay ; Zhong, Jixin. / MRP14 enhances the ability of macrophage to recruit T cells and promotes obesity-induced insulin resistance. In: International Journal of Obesity. 2019.
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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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AU - Razavi, Michael

AU - Rao, Xiaoquan

AU - Braunstein, Zachary

AU - Mao, Hong

AU - Toomey, Amelia C.

AU - Wang, Yunmei

AU - Simon, Daniel I.

AU - Zhao, Shi

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