Insulin resistance is present in almost all patients with
nonalcoholic steatohepatitis (
NAFLD), and
mitochondrial dysfunction likely plays a critical role in the progression of
fatty liver into
nonalcoholic steatohepatitis.
Rosiglitazone, a selective
ligand of
peroxisome proliferator-activated receptor gamma (
PPARgamma), is an
insulin sensitizer
drug that has been used in a number of
insulin-resistant conditions, including
NAFLD. The aim of this study was to analyze the effects of
rosiglitazone on the liver histology and mitochondrial function in a model of
NAFLD. All studies were carried out in wild-type and
leptin-deficient (ob/ob) C57BL/6J mice. Ob/ob mice were treated with 1 mg/kg/day, and activity of mitochondrial respiratory chain (MRC), beta-oxidation, lipid peroxidation,
glutathione content in mitochondria, and 3-tyrosine-nitrated
proteins in mitochondria were measured. In addition, histological and ultrastructural changes induced by
rosiglitazone were also noted.
Rosiglitazone treatment increased
liver steatosis, particularly microvesicular steatosis. In these animals, mitochondria were markedly swollen with cristae peripherally placed. In ob/ob mice, this
drug increased
PPARgamma protein expression and
lipid peroxide content in liver tissue and decreased
glutathione concentration in mitochondria.
Rosiglitazone suppressed the activity of complex I of the MRC in ob/ob mice, but did not affect beta-oxidation.
3-Tyrosine nitrated
mitochondrial proteins, significantly increased in ob/ob mice, were not modified by
rosiglitazone treatment.
CONCLUSION: