HSG4112 fully reverses adiposity in HFD-mice
We searched for HSG4112’s optimal therapeutic dose in HFD-mice. 6-week daily oral administration of HSG4112 at 10, 30, 100 mg·kg-1 dose led to significant dose-dependent weight loss of 4.0g (8.3%), 10g (21%), and 19g (40%), respectively, compared to HFD-mice administered with only vehicle (hereinafter Vehicle group) (Figure 2A ). At 100 mg·kg-1 dose, the body weight of HFD-mice completely normalized to 29.2g, equivalent to that of normal chow-diet fed mice (hereinafter Normal group); a representative image of Normal, Vehicle, and HSG4112-100mg·kg-1·day-1 group is shown in Figure 2B . For all following analysis, 100 mg·kg-1 was set as the optimal dose for HSG4112 in HFD-mice (hereinafter HSG4112 group).
Next, we investigated the effect of HSG4112 on parameters related to obesity. HSG4112 significantly reduced white adipose tissue (WAT) masses and adipocyte size in abdominal fat – periepididymal and perirenal adipose tissue – to a level equivalent to that of Normal group (Figure 2C-G ). HSG4112 retained relative gastrocnemius muscle mass (Figure 2H ), suggesting fat-selective reduction of body weight. In addition, serum leptin, insulin, and glucose concentration significantly decreased to a normal level (Figure 2I-K ), and HOMA-IR (Homeostasis Model Assessment Insulin Resistance) index was normalized (Figure 2L ); these data suggest that leptin and insulin sensitivity and glucose metabolism in obese animals have improved and normalized through HSG4112 administration. In summary, full normalization of adiposity was observed.