脂肪性肝炎
脂肪肝
脂肪变性
CD36
内科学
脂联素
内分泌学
药理学
生物
化学
医学
受体
肥胖
疾病
胰岛素抵抗
作者
Li Li,Haoming Sun,Jionghao Chen,Cong Ding,Xiaojun Yang,Hua Han,Qingzhu Sun
出处
期刊:Cell Reports
[Elsevier]
日期:2023-07-01
卷期号:42 (7): 112697-112697
被引量:3
标识
DOI:10.1016/j.celrep.2023.112697
摘要
Summary
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.
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