EphA3 deficiency in the hypothalamus promotes high-fat diet-induced obesity in mice.
EphA3 deficiency in the hypothalamus promotes high-fat diet-induced obesity in mice.
复制标题
DOI：
10.7555/jbr.36.20220168
复制
发表时间：
2022-11-28
影响因子：
2.3
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Zhang J;Chen Y;Yan L;Zhang X;Zheng X;Qi J;Yang F;Li J
促红细胞生成素产生型肝细胞癌A3 （EphA3）是酪氨酸激酶受体- eph受体最大亚家族的成员。先前的研究表明EphA3与组织发育有关。最近，我们发现饮食性肥胖（DIO）小鼠下丘脑中EphA3的表达升高。然而，EphA3在下丘脑控制的能量代谢中的作用尚不清楚。在目前的研究中，我们证明了通过CRISPR/ cas9介导的基因编辑缺失下丘脑的EphA3会促进高脂肪饮食喂养的雄性小鼠的肥胖，而不是正常鼠粮喂养的雄性小鼠。此外，下丘脑EphA3的缺失通过增加食物摄入和减少能量消耗来促进高脂肪DIO。EphA3的敲低导致GT1-7细胞内囊泡变小。目前的研究表明，下丘脑EphA3在促进DIO中起重要作用。
Erythropoietin-producing hepatocellular carcinoma A3 (EphA3) is a member of the largest subfamily of tyrosine kinase receptors—Eph receptors. Previous studies have shown that EphA3 is associated with tissue development. Recently, we have found that the expression of EphA3 is elevated in the hypothalamus of mice with diet-induced obesity (DIO). However, the role of EphA3 in hypothalamic-controlled energy metabolism remains unclear. In the current study, we demonstrated that the deletion of EphA3 in the hypothalamus by CRISPR/Cas9-mediated gene editing promotes obesity in male mice with high-fat diet feeding rather than those with normal chow diet feeding. Moreover, the deletion of hypothalamic EphA3 promotes high-fat DIO by increasing food intake and reducing energy expenditure. Knockdown of EphA3 leads to smaller intracellular vesicles in GT1-7 cells. The current study reveals that hypothalamic EphA3 plays important roles in promoting DIO.