Obesity-induced inflammation, characterized by augmented infiltration and altered balance of macrophages, is a critical component of systemic insulin resistance. Chemokine-chemokine receptor system plays a vital role in the macrophages accumulation. CC-Chemokine Receptor-like 2 (Ccrl2) is one of the receptors of Chemerin, which is a member of atypical chemokine receptors (ACKR) family, reported taking part in host immune responses and inflammation-related conditions. In our study, we found ccrl2 expression significantly elevated in visceral adipose tissue (VAT) of high fat diet (HFD) induced obese mice and ob/ob mice. Systemic deletion of Ccrl2 gene aggravated HFD induced obesity and insulin resistance and ccrl2^−/− mice showed aggravated VAT inflammation and increased M1/M2 macrophages ratio, which is due to the increase of macrophages chemotaxis in Ccrl2 deficiency mice. Cumulatively, these results indicate that Ccrl2 has a critical function in obesity and obesity-induced insulin resistance via mediating macrophages chemotaxis.

肥胖引起的炎症以增加浸润和改变巨噬细胞平衡为特征，是全身性胰岛素抵抗的关键组成部分。趋化因子-趋化因子受体系统在巨噬细胞的积累中起着至关重要的作用。CC-趋化因子受体样 2 (Ccrl2) 是 Chemerin 的受体之一，它是非典型趋化因子受体 (ACKR) 家族的成员，据报道参与宿主免疫反应和炎症相关疾病。在我们的研究中，我们发现ccrl2表达在高脂肪饮食 (HFD) 诱导的肥胖小鼠和ob/ob小鼠的内脏脂肪组织 (VAT) 中显着升高。Ccrl2基因的全身缺失加重了HFD诱导的肥胖和胰岛素抵抗以及ccrl2 ^-/-小鼠表现出加重的 VAT 炎症和增加的 M1/M2 巨噬细胞比率，这是由于 Ccrl2 缺陷小鼠中巨噬细胞趋化性的增加。累积地，这些结果表明Ccrl2通过介导巨噬细胞趋化性在肥胖和肥胖诱导的胰岛素抵抗中具有关键作用。