HSG4112 ameliorates features of fatty liver in HFD-mice
In the same set of animals, we examined the liver weight, histology, and blood parameters associated with fatty liver, because obesity is often accompanied by and causal to the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), which are characterized by varying degrees of hepatic steatosis, lobular inflammation, cell ballooning, and fibrosis (Bedossa, 2017).
HSG4112 normalized the absolute liver weight and histology of HFD-mice (Figure 3A, B ). In terms of the NAFLD activity score (NAS), HSG4112 fully reduced the steatosis and inflammation score, and the concurrent overall NAS score of HFD-mice, up to Normal group’s level (Figure 3C, D, E ). Fibrosis was not significantly induced in Vehicle group (Figure 3F ), and hepatocyte ballooning was not induced at all in animals of all groups. Together, HSG4112 improved liver histology mainly through resolution of inflammation and steatosis.
In terms of blood parameters, HSG4112 did not significantly reduce serum triglyceride level (Figure 3G ) but significantly reduced and normalized total cholesterol (Figure 3H ) and LDL-cholesterol level (Figure 3I ). HDL-cholesterol level was not significantly influenced (Figure 3I ). Serum ALT level was significantly reduced (Figure 3J ), while AST level showed decreasing trend (Figure 3K ). Serum triglyceride and HDL-cholesterol level in murine models they are difficult to interpret and to apply to fatty liver status (Van Herck, Vonghia and Francque, 2017). In sum, HSG4112 normalized most of the relevant blood parameters, indicating robust amelioration of fatty liver.