Life Style-Related Diseases of the Digestive System:Gene Expression in Nonalcoholic Steatohepatitis Patients and Treatment Strategies

Journal of Pharmacological Sciences

Hiroki Endo⁵  Shuichi Tsutsumi⁴  Hirokazu Takahashi⁵  Koichiro Wada³  Kyoko Yoneda⁵  Atsushi Nakajima⁵  Masato Yoneda⁵  Kikuko Hotta¹  Satoru Saito⁵  Shogo Yamamoto⁴  Ayako Tomimoto⁵  Hiroyuki Aburatani⁴  Koji Fujita⁵  Toshio Fujisawa⁵  Tomoyuki Iwasaki²  Yuichi Nozaki⁵ 

[1] Laboratories for Obesity, SNP Research Center, RIKEN, Japan;Division of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Japan;Department of Pharmacology, Osaka University Graduate School of Dentistry, Japan;Genome Science Division, Research Center for Advanced Science and Technology and Department of Pathology, Graduate School of Medicine, The University of Tokyo, Japan;Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Japan

关键词: life style-related disease;    nonalcoholic steatohepatitis (NASH);    nonalcoholic fatty liver disease (NAFLD);    microarray;    Gene Set Enrichment Analysis (GSEA);    pioglitazone;   

DOI  :  10.1254/jphs.FM0070063

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(49)Cited-By(7)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 (PPARγ) 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 PPARγ, 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 PPARγ pathway in NASH and the therapeutic utility of a PPARγ ligand.

【 授权许可】

Unknown