Metabolic effects of CCL5 deficiency in lean and obese mice

Hui Zhou; Xiyan Liao; Qin Zeng; Haowei Zhang; Jianfeng Song; Wanyu Hu; Xiaoxiao Sun; Yujin Ding; Dandan Wang; Yalun Xiao; Tuo Deng

doi:10.3389/fimmu.2022.1059687

Metabolic effects of CCL5 deficiency in lean and obese mice

Front Immunol. 2023 Jan 13:13:1059687. doi: 10.3389/fimmu.2022.1059687. eCollection 2022.

Authors

Hui Zhou^{1

2}, Xiyan Liao^{1

2}, Qin Zeng^{1

2}, Haowei Zhang^{1

2}, Jianfeng Song^{1

2}, Wanyu Hu^{1

2}, Xiaoxiao Sun^{1

2}, Yujin Ding^{1

2}, Dandan Wang^{1

2}, Yalun Xiao^{1

2}, Tuo Deng^{1

2

3}

Affiliations

¹ National Clinical Research Center for Metabolic Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
² Key Laboratory of Diabetes Immunology, Ministry of Education, and Metabolic Syndrome Research Center, The Second Xiangya Hospital of Central South University, Changsha, China.
³ Clinical Immunology Center, The Second Xiangya Hospital of Central South University, Changsha, China.

Abstract

Accumulation and activation of immunocytes in adipose tissues are essential to obesity-induced inflammation and insulin resistance. Chemokines are pivotal for the recruitment of immunocytes in adipose tissue during obesity. Chemokine (C-C motif) ligand 5 (CCL5) plays a vital role in the recruitment of immunocytes to sites of inflammation. CCL5 expression level is increased in obese adipose tissue from humans and mice. However, the role of CCL5 in obesity-induced adipose inflammation remains unclear. Our study found that the CCL5 expression level was increased in the epididymal white adipose tissue (eWAT) of obese mice, particularly in CD8⁺ T cells. CCL5 knockout (KO) mice exhibited better glucose tolerance than wild-type (WT) mice under lean conditions. In contrast, CCL5 KO mice were more insulin resistant and had severe hepatic steatosis than WT mice under obese conditions. Increased T cells in adipose tissue heaven adipose inflammation in obese CCL5 KO mice. The compensatory increased T cell-associated chemokines may account for increased T cell content in the eWAT of obese CCL5 KO mice. These findings imply that CCL5 deficiency exacerbates adipose inflammation and impairs insulin sensitivity in the metabolic tissues of obese mice.

Keywords: CCL5; adipose inflammation; chemokine; insulin resistance; obesity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes* / metabolism
Chemokine CCL5* / genetics
Chemokines
Inflammation / metabolism
Insulin Resistance*
Mice
Mice, Obese
Obesity / metabolism

Substances

Chemokine CCL5
Chemokines
Ccl5 protein, mouse

Grants and funding

This work was supported by the National Key R&D Program of China (2020YFA0803604), the National Natural Science Foundation of China (82130024, 81770868 and 91742103), the Science and Technology Innovation Program of Hunan Province (2020RC4009), the Project of Innovation-Driven Plan of Central South University (2020CX015), the Fundamental Research Funds for the Central Universities of Central South University (No.2022ZZTS0316, No.2022ZZTS0841, No. 2021zzts0364), and Hunan Provincial Innovation Foundation For Postgraduate (No.CX20210366).