Sympathetic blockage attenuates fasting-induced hepatic steatosis

Although the central nervous system coordinates whole-body metabolism, the neural mechanism for hepatic steatosis remains unclear. This study is aimed to explore the neural mechanism of fasting-induced hepatic steatosis. Mice were pretreated with 6-hydroxydopamine to block sympathetic nerve activity before fasting, and to explore the potential effects of chemical sympathectomy on fasting-induced hepatic steatosis and transcriptional changes. Twenty-four hours fasting led to obvious hepatic steatosis, low-core temperature, and similar effects to cold-induced white adipose lipolysis. The alterations in hepatic mRNA expression revealed that the hepatic lipid accumulation did not result from an increase in hepatic lipogenesis or a decrease in fatty acid oxidation but from enhanced fatty acid uptake as indicated by upregulation of CD36. Blockage of the sympathetic nervous system via chemical sympathectomy attenuated fasting-induced hepatic steatosis and suppressed CD36 upregulation in the liver, but did not obviously alter the expression of genes associated with lipogenesis or fatty acid oxidation. These findings indicate that the sympathetic nervous system orchestrates the mechanism for fasting-induced hepatic steatosis via modulating CD36 expression and adipose fat trafficking into the liver, which provides clues to reveal new targets for fatty liver diseases.