(The) role of Hes1 in the regulation of metabolic disease

Abstract

Hes1 is one of the most well-known targets of the Notch signaling pathway which is known as intracellular interaction and plays a role as a transcriptional factor. Although there are previous studies showing that Notch1, a receptor of the Notch signaling pathway, is involved in fat accumulation in the liver, little is known about the molecular mechanism. Increased Hes1 expression level was observed in liver tissues of mice fed with high-fat diet (HFD) and non-alcoholic fatty liver disease (NAFLD) patients. Based on this, in this paper, we performed whether Hes1 regulates NAFLD, a metabolic disease.When comparing the weight and size of the liver by feeding a HFD in mice that specifically inhibited Hes1 in the liver, it was confirmed that the weight and size of liver were decreased compared to the wild-type mice. Accordingly, genes related to the inflammatory response, TNFa, F4/80, and CCL2, and genes related to fat accumulation, such as C/EBPb, FABP4, CD36, SREBP, ACC1, and ACLY, were all decreased. The results were also shown in adipose tissue, and the expression of genes involved in thermogenesis, such as UCP1, was increased. In addition, when Hes1 is specifically inhibited in the liver, AST and ALT, which are indicators of liver toxicity, are decreased, but the overall metabolic rate is improved. It was confirmed that there is a correlation between hepatokine FGF21 and Hes1, and these results suggest that Hes1 might be a new therapeutic target for NAFLD.