title: Life style-related diseases of the digestive system: gene expression in nonalcoholic steatohepatitis patients and treatment strategies.
abstract: Nonalcoholic steatohepatitis (NASH) is a subset of nonalcoholic fatty liver disease (NAFLD) and sometimes progresses to cirrhosis and liver failure. We analyzed the expression profiles of approximately 50,000 genes and biological pathways in NASH patients in comparison with simple steatosis patients by using the analytical technique of GSEA (Gene Set Enrichment Analysis) by DNA microarrays. Although expressions of various genes were altered, GSEA showed clearly lower expression of nuclear receptors, including the peroxisome proliferator-activated receptor gamma (PPARgamma) pathway. In a preliminary study we therefore investigated the therapeutic effect of low-dose pioglitazone (15 mg/day per body for 24 weeks), a synthetic ligand for PPARgamma, in 12 NASH patients. A decrease in aminotransferase (ALT) values to within the normal range was observed in 7 (58.3%) of the patients, and because the dose of pioglitazone was lower than that ordinarily used, no side effects, such as fatigue, lower extremity edema, or weight gain, were observed. In conclusion, the results confirmed involvement of the PPARgamma pathway in NASH and the therapeutic utility of a PPARgamma ligand.
authors.affiliation: Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Endo
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Ayako
authors.initials: A
authors.lastname: Tomimoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yoneda
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Shogo
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Koichiro
authors.initials: K
authors.lastname: Wada
authors.forename: Kikuko
authors.initials: K
authors.lastname: Hotta
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000410:Alanine Transaminase; D000077205:Pioglitazone