Liver is an important organ for regulating glucose and lipid metabolism. Recent studies have shown that bone morphogenetic proteins (BMPs) may play important roles in regulating glucose and lipid metabolism. In our previous studies, we demonstrated that BMP4 significantly inhibits hepatic steatosis and lowers serum triglycerides, playing a protective role against the progression of non-alcoholic fatty liver disease (NAFLD). However, the direct impact of BMP4 on hepatic glucose metabolism is poorly understood. Here, we investigated the regulatory roles of BMP4 in hepatic glucose metabolism. Through a comprehensive analysis of the 14 types of BMPs, we found that BMP4 was one of the most potent BMPs in promoting hepatic glycogen accumulation, reducing the level of glucose in hepatocytes and effecting the expression of genes related to glucose metabolism. Mechanistically, we demonstrated that BMP4 reduced the hepatic glucose levels through the activation of mTORC2 signaling pathway in vitro and in vivo. Collectively, our findings strongly suggest that BMP4 may play an essential role in regulating hepatic glucose metabolism. This knowledge should aid us to understand the molecular pathogenesis of NAFLD, and may lead to the development of novel therapeutics by exploiting the inhibitory effects of BMPs on hepatic glucose and lipid metabolism.

肝脏是调节糖脂代谢的重要器官。最近的研究表明，骨形态发生蛋白（BMPs）可能在调节葡萄糖和脂质代谢中发挥重要作用。在我们之前的研究中，我们证明 BMP4 显着抑制肝脏脂肪变性并降低血清甘油三酯，对非酒精性脂肪肝 (NAFLD) 的进展起到保护作用。然而，BMP4 对肝脏葡萄糖代谢的直接影响知之甚少。在这里，我们研究了 BMP4 在肝脏葡萄糖代谢中的调节作用。通过对14种BMPs的综合分析，我们发现BMP4是促进肝糖原积累最有效的BMPs之一，降低肝细胞中的葡萄糖水平并影响与葡萄糖代谢相关的基因的表达。从机制上讲，我们证明 BMP4 通过激活 mTORC2 信号通路降低肝脏葡萄糖水平体外和体内。总的来说，我们的研究结果强烈表明 BMP4 可能在调节肝脏葡萄糖代谢中发挥重要作用。这些知识应该有助于我们了解 NAFLD 的分子发病机制，并可能通过利用 BMPs 对肝脏葡萄糖和脂质代谢的抑制作用来开发新的治疗方法。