Department of Animal Science, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Department of Biomedicine, Future Agriculture Institute, Northwest A&F University, Yangling, Shaanxi, China.
Cell Rep. 2023 Jul 25;42(7):112697. doi: 10.1016/j.celrep.2023.112697. Epub 2023 Jun 24.
The therapeutic administration of recombinant proteins is utilized in a multitude of research studies for treating various diseases. In this study, we investigate the therapeutic potential of Orosomucoid 2 (Orm2), an acute phase protein predominantly secreted by hepatocytes, for treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Our results show that high Orm2 expression prevents high-fat-diet (HFD)-induced obesity in mice. Pharmacological administration of recombinant ORM2 protein ameliorates hepatic steatosis, inflammation, hepatocyte injury, and fibrosis in mouse livers afflicted by NAFLD and NASH under dietary stress. Orm2 knockout mice develop spontaneous obesity under a regular diet and exacerbate HFD-induced steatosis, steatohepatitis, and fibrosis. Mechanistically, Orm2 deletion activates the Erk1/2-PPARγ-Cd36 signaling pathway, increasing fatty acid uptake and absorption in hepatocytes and mice. Overall, our findings underscore the critical role of Orm2 in preventing NASH and associated NAFLD in the context of obesity.
重组蛋白的治疗性给药在许多研究中被用于治疗各种疾病。在这项研究中，我们研究了急性期蛋白 Orosomucoid 2（Orm2）的治疗潜力，它主要由肝细胞分泌，用于治疗非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）。我们的结果表明，高表达 Orm2 可预防高脂肪饮食（HFD）诱导的肥胖。在饮食应激下，重组 ORM2 蛋白的药理学给药可改善 NAFLD 和 NASH 小鼠肝脏的脂肪变性、炎症、肝细胞损伤和纤维化。Orm2 基因敲除小鼠在正常饮食下自发肥胖，并加重 HFD 诱导的脂肪变性、肝炎和纤维化。从机制上讲，Orm2 缺失激活了 Erk1/2-PPARγ-Cd36 信号通路，增加了肝细胞和小鼠中脂肪酸的摄取和吸收。总之，我们的研究结果强调了 Orm2 在肥胖背景下预防 NASH 和相关 NAFLD 的关键作用。
