National Clinical Research Center for Metabolic Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
Key Laboratory of Diabetes Immunology, Ministry of Education, and Metabolic Syndrome Research Center, The Second Xiangya Hospital of Central South University, Changsha, China.
Front Immunol. 2023 Jan 13;13:1059687. doi: 10.3389/fimmu.2022.1059687. eCollection 2022.
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.
免疫细胞在脂肪组织中的积累和激活对于肥胖引起的炎症和胰岛素抵抗至关重要。趋化因子对于肥胖期间脂肪组织中免疫细胞的募集至关重要。趋化因子 (C-C 基序) 配体 5 (CCL5) 在招募免疫细胞到炎症部位方面起着至关重要的作用。CCL5 的表达水平在肥胖人类和小鼠的脂肪组织中增加。然而，CCL5 在肥胖引起的脂肪炎症中的作用尚不清楚。我们的研究发现，肥胖小鼠附睾白色脂肪组织 (eWAT) 中的 CCL5 表达水平增加，特别是在 CD8 T 细胞中。在瘦条件下，CCL5 敲除 (KO) 小鼠比野生型 (WT) 小鼠具有更好的葡萄糖耐量。相比之下，在肥胖条件下，CCL5 KO 小鼠比 WT 小鼠更容易出现胰岛素抵抗和严重的肝脂肪变性。脂肪组织中 T 细胞的增加导致肥胖 CCL5 KO 小鼠的脂肪炎症。代偿性增加的 T 细胞相关趋化因子可能解释了肥胖 CCL5 KO 小鼠 eWAT 中 T 细胞含量的增加。这些发现表明 CCL5 缺乏会加剧肥胖小鼠代谢组织中的脂肪炎症和损害胰岛素敏感性。
