Hepatic steatosis caused by
starvation, resulting in
non-alcoholic fatty liver disease (
NAFLD), has been a research topic of human clinical and animal experiments. To understand the molecular mechanisms underlying the triggering of abnormal liver metabolism by
starvation, thus inducing hepatic
lipid accumulation, we used zebrafish larvae to establish a
starvation-induced hepatic steatosis model and conducted comparative transcriptome analysis by
RNA-seq. We demonstrated that the incidence of larvae steatosis is positively correlated with
starvation time. Under
starvation conditions, the
fatty acid transporter (slc27a2a and slc27a6-like) and
fatty acid translocase (cd36) were up-regulated significantly to promote extrahepatic
fatty acid uptake. Meanwhile,
starvation inhibits the hepatic
fatty acid metabolism pathway but activates the de novo lipogenesis pathway to a certain extent. More importantly, we detected that the expression of numerous
apolipoprotein genes was downregulated and the secretion of
very low density lipoprotein (VLDL) was inhibited significantly. These data suggest that
starvation induces hepatic steatosis by promoting extrahepatic
fatty acid uptake and lipogenesis, and inhibits hepatic
fatty acid metabolism and
lipid transport. Furthermore, we found that
starvation-induced hepatic steatosis in zebrafish larvae can be rescued by targeting the knockout cd36 gene. In summary, these findings will help us understand the pathogenesis of
starvation-induced
NAFLD and provide important theoretical evidence that cd36 could serve as a potential target for the treatment of
NAFLD.