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.