title: The peroxisome proliferator-activated receptor-gamma agonist, pioglitazone, inhibits fat accumulation and fibrosis in the livers of rats fed a choline-deficient, l-amino acid-defined diet.
abstract: Administration of a choline-deficient, l-amino acid-defined (CDAA) diet to rats causes steatohepatitis, hepatic fibrosis, and hepatocellular carcinoma, a pathology similar to that observed in non-alcoholic steatohepatitis (NASH). The aim of this study was to evaluate if a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, pioglitazone (PGZ), could ameliorate CDAA diet-induced fatty liver and cirrhosis. Rats were fed a CDAA diet for 1 week and were given the CDAA diet for an additional week with or without PGZ (2-week model). Also, after administration of the CDAA diet for 12 weeks, rats were administered the CDAA diet for an additional 4 weeks with or without PGZ (16-week model). The CDAA diet, administered for either one or 12 weeks, induced fatty liver or cirrhosis with up-regulation of hepatic PPAR-gamma expression, respectively. In the 2-week model, rats treated with PGZ for 1 week demonstrated significantly lower hepatic triglyceride content and serum levels of tumor necrosis factor-alpha. In the 16-week model, treatment for 4 weeks with PGZ ameliorated hepatic fibrosis with a decrease in the expression of procollagen, alpha-smooth muscle actin, and transforming growth factor-beta1 in comparison to rats without PGZ. These results suggest that PPAR-gamma agonist is a potential therapeutic modality to treat NASH.
authors.affiliation: Department of Internal Medicine II, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889 1692, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uto
authors.forename: Chihiro
authors.initials: C
authors.lastname: Nakanishi
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Satoru
authors.initials: S
authors.lastname: Hasuike
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kusumoto
authors.forename: Hiroo
authors.initials: H
authors.lastname: Abe
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Numata
authors.forename: Kenji
authors.initials: K
authors.lastname: Nagata
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi