Life style-related diseases of the digestive system: gene expression in nonalcoholic steatohepatitis patients and treatment strategies.
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.
Yoneda
Masato
M
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Endo
Hiroki
H
Nozaki
Yuichi
Y
Tomimoto
Ayako
A
Fujisawa
Toshio
T
Fujita
Koji
K
Yoneda
Kyoko
K
Takahashi
Hirokazu
H
Saito
Satoru
S
Iwasaki
Tomoyuki
T
Yamamoto
Shogo
S
Tsutsumi
Shuichi
S
Aburatani
Hiroyuki
H
Wada
Koichiro
K
Hotta
Kikuko
K
Nakajima
Atsushi
A
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
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000410:Alanine Transaminase; D000077205:Pioglitazone