Abstract：
Obesity is a major health crisis in the modern society. Studies have shown that the consumption of a high-fat diet (HFD) induces hypothalamic inflammation and leptin resistance, which consequently favours body mass gain. Actin related protein 2/3 complex subunit 1 (ARPC1B), an actin-binding protein, is highly expressed in immune cells. Recent studies have shown that ARPC1B has a certain anti-inflammatory effect. While ARPC1B expression is decreased in the hypothalamus of mice fed a HFD, the role of ARPC1B in HFD-induced obesity remains unclear. Thus, we investigated whether ARPC1B up-regulation in the hypothalamic arcuate nucleus (ARC) could inhibit the development of obesity. Herein, ARPC1B overexpression lentiviral particles were stereotaxically injected into the ARC of male C57BL/6J mice (7 weeks old) fed with HFD. Overexpression of ARPC1B in the hypothalamic ARC attenuated HFD-induced ARC inflammation, reduced body-weight gain and feed efficiency. Furthermore, up-regulation of ARC ARPC1B improved the glucose tolerance and reduced subcutaneous/epididymal fat mass accumulation, which decreased the serum total cholesterol, serum triglyceride and leptin levels. In addition, upon ARPC1B overexpression in the hypothalamic ARC, intraperitoneal injection of leptin increased the phosphorylation level of signal transducer and activator of transcription 3 (STAT3), an important transcription factor for leptin\'s action, in the ARC of obese mice. Accordingly, we suggest that up-regulation of ARPC1B in the hypothalamic ARC may improve the HFD-induced hypothalamic inflammation and leptin resistance. Our findings demonstrate that ARPC1B is a promising target for the treatment of diet-induced obesity.
摘要：
肥胖是现代社会的一大健康危机。研究表明，高脂饮食（HFD）的消费诱导下丘脑炎症和瘦素抵抗，因此有利于增加体重。肌动蛋白相关蛋白2/3复合物亚基1(ARPC1B),一种肌动蛋白结合蛋白，在免疫细胞中高度表达。最近的研究表明ARPC1B具有一定的抗炎作用。虽然ARPC1B表达在HFD喂养的小鼠的下丘脑中降低,ARPC1B在HFD诱导的肥胖中的作用尚不清楚.因此，我们研究了下丘脑弓状核(ARC)ARPC1B上调是否能抑制肥胖的发生.在这里，将ARPC1B过表达慢病毒颗粒立体定向注射到用HFD喂养的雄性C57BL/6J小鼠(7周龄)的ARC中。下丘脑ARC中ARPC1B的过表达减弱了HFD诱导的ARC炎症,降低体重增加和饲料效率。此外，ARCARPC1B的上调改善了葡萄糖耐量并减少了皮下/附睾脂肪量的积累，降低了血清总胆固醇，血清甘油三酯和瘦素水平。此外,在下丘脑ARC中ARPC1B过表达时，腹腔注射瘦素可增加信号转导和转录激活因子3(STAT3)的磷酸化水平,瘦素作用的重要转录因子，在肥胖小鼠的ARC中。因此，我们提示,下丘脑ARC中ARPC1B的上调可能会改善HFD诱导的下丘脑炎症和瘦素抵抗.我们的发现表明，ARPC1B是治疗饮食诱导的肥胖的有希望的靶标。
