Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.
Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.
Biomed Pharmacother. 2019 Dec;120:109503. doi: 10.1016/j.biopha.2019.109503. Epub 2019 Oct 4.
Nonalcoholic fatty liver disease (NAFLD) is a common and complex metabolic disorder. Despite the widespread concern, there are still few effective treatments except lifestyle interventions. Nuclear receptor subfamily 2 group E member 1 (Nr2e1) is a transcription factor which regulates many biological processes, including development, growth, and differentiation of nerve cells. However, its specific function in hepatocyte is still unknown. In the present study, we found that the expression of Nr2e1 decreased in the livers of high-fat diet-fed mice. We generated Nr2e1 knockout (KO) mice and studied whether Nr2e1 ablation was related to NAFLD. We found that typical pathological features of NAFLD, including insulin resistance, hepatic steatosis, and inflammation, were present in Nr2e1-KO mice or high-fat diet-induced mice models. In conclusion, Nr2e1 ablation promotes liver steatosis and systemic insulin resistance. Nr2e1 may play a protective role in the formation of NAFLD and may serve as a worthy therapeutic target for NAFLD.
非酒精性脂肪性肝病 (NAFLD) 是一种常见且复杂的代谢性疾病。尽管人们普遍关注，但除了生活方式干预外，目前仍缺乏有效的治疗方法。核受体亚家族 2 组 E 成员 1 (Nr2e1) 是一种转录因子，可调节许多生物学过程，包括神经细胞的发育、生长和分化。然而，其在肝细胞中的具体功能尚不清楚。在本研究中，我们发现 Nr2e1 的表达在高脂肪饮食喂养的小鼠肝脏中降低。我们生成了 Nr2e1 敲除 (KO) 小鼠，并研究了 Nr2e1 缺失是否与 NAFLD 有关。我们发现 Nr2e1-KO 小鼠或高脂肪饮食诱导的小鼠模型存在 NAFLD 的典型病理特征，包括胰岛素抵抗、肝脂肪变性和炎症。总之，Nr2e1 缺失促进肝脏脂肪变性和全身胰岛素抵抗。Nr2e1 可能在 NAFLD 的形成中发挥保护作用，可能成为 NAFLD 的一个有价值的治疗靶点。
