Non-
alcoholic steatohepatitis (NASH), a type of
fatty liver disease, is characterized by excessive
inflammation and fat accumulation in the liver.
Peroxisome proliferator-activated receptor γ (PPARγ) agonist
rosiglitazone has great potential in protecting against the development of NASH. However, long-term usage of
rosiglitazone probably leads to many adverse reactions. In this research, GVS-12 was designed and synthesized as a PPARγ agonist with high selectivity, evidenced by increasing the activity of the PPARγ reporter gene and promoting the
mRNA expression of the PPARγ responsive gene cluster of differentiation 36 (CD36). It was noteworthy that GVS-12 could ameliorate dysfunction and
lipid accumulation by down-regulating the
mRNA expression of interleukin-1β (IL-1β),
interleukin-6 (IL-6) and
tumor necrosis factor-α (TNF-α) in the liver of high fat diet (HFD)-induced rats and
palmitic acid (PA)-stimulated
hepatocellular carcinoma G2 (HepG2) cells. Moreover, PPARγ
siRNA (siPPARγ) markedly diminished GVS-12 induced the down-regulation of
mRNA expression of IL-1β,
IL-6 and TNF-α in PA-stimulated HepG2 cells. Additionally, GVS-12 could reduce the phosphorylation level of STAT3 and up-regulate the
protein expression of a suppressor of
cytokine signaling 3 (SOCS3), which could be reversed by siPPARγ. In detail, SOCS3
siRNA (siSOCS3) diminished the inhibitory effect of GVS-12 on the
mRNA expression of IL-1β,
IL-6 and TNF-α. In conclusion, GVS-12 suppressed the development of NASH by down-regulating the
mRNA expression of IL-1β,
IL-6 and TNF-α via PPARγ/STAT3 signaling pathways.