近日，来自美国西南医学中心的研究人员发现降低糖尿病病人和非酒精性脂肪肝病肝脏内一种高浓度的脂质分子可以快速改善胰岛素敏感性。相关研究结果发表在国际学术期刊Cell metabolism上。

　　胰岛素是一种重要的激素，能够帮助机体将糖转化为能量，吸收营养同时将多余的糖转化为脂肪。胰岛素敏感性降低会造成这些生理过程的效率下降，导致糖尿病和脂肪肝的发生。

　　西南医学中心的研究人员发现在高脂饮食小鼠模型中过表达酸性神经酰胺酶能够使小鼠的胰岛素敏感性恢复正常水平。当身体内脂肪酸过多而机体不能及时将其消耗，多余的脂肪酸会转变为神经酰胺，而过多的神经酰胺会影响胰岛素信号，导致胰岛素抵抗，进而发生糖尿病和非酒精性脂肪肝。

　　在高脂饮食小鼠模型的肝脏中过表达酸性神经酰胺酶能够防止脂肪肝的发生，同时促进胰岛素在肝脏和脂肪组织内发挥的作用。在脂肪组织内过表达酸性神经酰胺酶也能够防止脂肪肝的发生，并改善系统性胰岛素敏感性。无论是在肝脏还是在脂肪组织内诱导表达酸性神经酰胺酶都会降低肝脏神经酰胺的浓度，这一过程的发生可以使胰岛素敏感性正常化。

　　研究人员还发现多余的神经酰胺会被转化为鞘氨醇，而这两种脂类物质对代谢信号途径具有不同的影响。太多的神经酰胺会导致胰岛素抵抗和炎症的发生，而鞘氨醇则会导致相反的情况发生。

　　总的来说，这项研究发现肝脏和脂肪组织的鞘氨醇之间存在一种快速的交互作用，这对于调节葡萄糖代谢和肝脏对脂类物质的摄取具有重要影响。同时，这项研究还为糖尿病和脂肪肝的治疗提供了重要线索。

　　doi:10.1016/j.cmet.2015.06.007

　　Targeted Induction of Ceramide Degradation Leads to Improved Systemic Metabolism and Reduced Hepatic Steatosis

　　Jonathan Y. Xia1, 4, William L. Holland1, 4, Christine M. Kusminski1, Kai Sun1, Ankit X. Sharma1, Mackenzie J. Pearson1, Angelica J. Sifuentes1, Jeffrey G. McDonald2, Ruth Gordillo1, Philipp E. Scherer

　　Sphingolipids have garnered attention for their role in insulin resistance and lipotoxic cell death. We have developed transgenic mice inducibly expressing acid ceramidase that display a reduction in ceramides in adult mouse tissues. Hepatic overexpression of acid ceramidase prevents hepatic steatosis and prompts improvements in insulin action in liver and adipose tissue upon exposure to high-fat diet. Conversely, overexpression of acid ceramidase within adipose tissue also prevents hepatic steatosis and systemic insulin resistance. Induction of ceramidase activity in either tissue promotes a lowering of hepatic ceramides and reduced activation of the ceramide-activated protein kinase C isoform PKCζ, though the induction of ceramidase activity in the adipocyte prompts more rapid resolution of hepatic steatosis than overexpression of the enzyme directly in the liver. Collectively, our observations suggest the existence of a rapidly acting "cross-talk" between liver and adipose tissue sphingolipids, critically regulating glucose metabolism and hepatic lipid uptake.