Down-Regulating the High Level of 17-Beta-Hydroxysteroid Dehydrogenase 13 Plays a Therapeutic Role for Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and there is no specific drug to treat it. Recent results showed that 17-beta-hydroxysteroid dehydrogenase type 13 (HSD17B13) is associated with liver diseases, but these conclusions are controversial. Here, we showed that HSD17B13 was more highly expressed in the livers of NAFLD patients, and high expression was induced in the livers of murine NAFLD models and cultural hepatocytes treated using various etiologies. The high HSD17B13 expression in the hepatocytes facilitated the progression of NAFLD by directly stabilizing the intracellular lipid drops and by indirectly activating hepatic stellate cells. When HSD17B13 was overexpressed in the liver, it aggravated liver steatosis and fibrosis in mice fed with a high-fat diet, while down-regulated the high expression of HSD17B13 by short hairpin RNAs produced a therapeutic effect in the NAFLD mice. We concluded that high HSD17B13 expression is a good target for the development of drugs to treat NAFLD.