Bing Zhou, Yunchen Luo, Nana Ji et al, Orosomucoid 2 maintains hepatic lipid homeostasis through suppression of de novo lipogenesis4808 Accesses, nature metabolism, 2022. (IF: 18.9)

Abstract: This study identifies the hepatokine orosomucoid (ORM) 2 as a crucial regulator of new fat production in the liver. Both liver and plasma ORM2 levels are significantly reduced in obese mice and humans with NAFLD. The research demonstrates that ORM2 is vital for maintaining lipid balance in the liver and throughout the body. Mechanistically, ORM2 interacts with the inositol 1, 4, 5-trisphosphate receptor type 2 to trigger AMP-activated protein kinase signaling, which in turn suppresses the sterol regulatory element binding protein 1c-driven program of lipogenic genes. Importantly, administering recombinant ORM2 protein or a stabilized ORM2–FC fusion protein via intraperitoneal injections significantly alleviated liver fat accumulation, inflammation, and atherosclerosis in mouse models, without negatively impacting body weight or food consumption.

摘要：在这项研究中，我们发现肝源性蛋白口服黏蛋白（ORM）2是肝脏新脂肪生成的关键调节因子。在肥胖的小鼠模型和NAFLD患者中，肝脏和血浆中的ORM2水平显著降低。通过多种功能丧失和功能获得的研究，证明ORM2对于维持肝脏和全身脂质稳态至关重要。在分子机制方面，ORM2与肌醇1,4,5-三磷酸受体2型结合，激活24 CitationsAMP激活蛋白激酶信号通路，从而抑制固醇调节元件结合蛋白1c介导的脂肪生成基因程序。在临床前的小鼠模型中，通过腹腔注射重组ORM2蛋白或稳定的ORM2-FC融合蛋白显著改善了肝脏脂肪变性、肝炎和动脉粥样硬化，且对体重或食物摄入没有不良影响。