Study on role of PHF2 in the development of non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is caused by excessive fat accumulation in the hepatocytes. Mild steatosis may develop into aggressive forms of Hepatic fibrosis, cirrhosis and carcinoma. Plant homeodomain finger 2 (PHF2), a JmjC histone demethylase, is known as the demethylase of the Histone H3K9 while it binds to H3K4me3 with the PHD domain. PHF2 is known to have associated with metabolism-related transcription factors. In this study, we identified the role of PHF2 in the progression of hepatic steatosis. For in vivo study, WT and PHF2 overexpressed TG mice were fed normal diet or high fat diet for 8 weeks. And then, Liver steatosis and blood chemistry were analyzed. The expression level of protein and genes involved in liver lipid metabolism were measured. For in-vitro study, PHF2 was stably silenced in HepG2, human liver cell line. Overexpression of PHF2 attenuated lipid accumulation in liver and insulin tolerance in mice fed with high fat diet. The expression of lipogenic genes was decreased in TG mice liver. In in vitro study, increased levels of lipogenic genes were confirmed in PHF2 knock-down stable cell. In addition, we found that PHF2 directly interacts with SREBP1c through protein-protein interaction. These results suggest that PHF2 plays a role as a repressor in the progression of hepatic steatosis through the association with SREBP1