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.