Thiazolidinediones (TZDs) markedly reduce hepatic steatosis in both rodents and humans. However, the effects and mechanisms of action of TZDs on hepatic
fibrosis remain unclear. The aim of the present study was to determine the effects of TZDs on histological changes in the liver and on the modulation by
adiponectin via the
AMP-activated protein kinase (AMPK) signalling pathway in rats with non-
alcoholic steatohepatitis (NASH). Forty rats were divided into normal control, high-fat diet (HFD),
pioglitazone control and
pioglitazone intervention groups. After 24 weeks treatment with
pioglitazone (10 mg/kg per day by gavage), changes in liver histology, serum aminotransaminase,
triglyceride (TG),
free fatty acid (FFA),
glucose,
insulin,
adiponectin and
transforming growth factor (TGF)-β1 concentrations and hepatic
adiponectin, AMPK, α-smooth muscle actin (α-SMA) and
collagen I expression were evaluated. The degree of hepatic steatosis and
fibrosis was significantly higher in HFD-induced NASH rats compared with normal controls, as were serum concentrations of aminotransaminase, TG, FFA,
glucose,
insulin and TGF-β1 and hepatic expression of α-SMA and
collagen I
protein. Serum
adiponectin concentrations and hepatic expression of
adiponectin mRNA and AMPK
protein were significantly lower in the HFD-induced NASH rats compared with the normal control.
Pioglitazone significantly reduced the degree of hepatic steatosis and
fibrosis, as well as serum concentrations of aminotransaminase, TG, FFA,
glucose,
insulin and TGF-β1 and hepatic expression of α-SMA and
collagen I
protein. In addition,
pioglitazone significantly increased serum
adiponectin concentrations and hepatic expression of
adiponectin mRNA and AMPK
protein. In conclusion, the TZD
pioglitazone improved hepatic
fibrosis in rats with NASH by upregulating
adiponectin expression and activating AMPK, thus subsequently inhibiting the activation of hepatic stellate cells and the overproduction of extracellular matrix.