Sympathetic blockage attenuates fasting-induced hepatic steatosis

Abstract

Background and AimAlthough it is clear that 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. MethodsMice were pretreated with 6-hydroxydopamine to block sympathetic nerve activity before fasting, and explored the potential effects of chemical sympathectomy on fasting-induced hepatic steatosis and transcriptional changes. ResultsProlonged 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 the increase of hepatic lipogenesis or the decrease of fatty acid oxidation but from the enhanced fatty acid uptake as indicated by the 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. ConclusionsThese 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. HIGHLIGHTSO_LIProlonged fasting causes obvious hepatic steatosis C_LIO_LISympathectomy attenuates fasting-induced hepatic steatosis C_LIO_LISympathectomy attenuates steatosis via suppressing CD36 upregulation C_LI IN BRIEFProlonged fasting contributes to sympathetic hyperactivity, but its role in the pathogenesis of hepatic steatosis remains unclear. Here, we found prolonged fasting led to obvious hepatic steatosis, low core temperature, and subsequent sympathetic stimulation that promoted white adipose lipolysis, hepatic upregulation of CD36, and adipose fat trafficking into the liver.