title: Changes in hepatic gene expression upon oral administration of taurine-conjugated ursodeoxycholic acid in ob/ob mice.
abstract: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and associated with considerable morbidities. Unfortunately, there is no currently available drug established to treat NAFLD. It was recently reported that intraperitoneal administration of taurine-conjugated ursodeoxycholic acid (TUDCA) improved hepatic steatosis in ob/ob mice. We hereby examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER) stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice. Compared to the control ob/ob mice, TUDCA treated ob/ob mice revealed markedly reduced liver fat stained by oil red O (44.2±5.8% vs. 21.1±10.4%, P<0.05), whereas there was no difference in body weight, oral glucose tolerance, insulin sensitivity, and ER stress. Microarray analysis of hepatic gene expression demonstrated that oral TUDCA treatment mainly decreased the expression of genes involved in de novo lipogenesis among the components of lipid homeostasis. At pathway levels, oral TUDCA altered the genes regulating amino acid, carbohydrate, and drug metabolism in addition to lipid metabolism. In summary, oral TUDCA treatment decreased hepatic steatosis in ob/ob mice by cooperative regulation of multiple metabolic pathways, particularly by reducing the expression of genes known to regulate de novo lipogenesis.
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Yang
authors.forename: Jin Taek
authors.initials: JT
authors.lastname: Kim
authors.forename: Jouhyun
authors.initials: J
authors.lastname: Jeon
authors.forename: Ho Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Hong Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.forename: Young Min
authors.initials: YM
authors.lastname: Cho
mesh_terms: D000284:Administration, Oral; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D050260:Carbohydrate Metabolism / Q000187:drug effects; D016000:Cluster Analysis; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000150:complications* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013654:Taurine / Q000008:administration & dosage / Q000494:pharmacology*; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; C030141:taurine-ursodeoxycholate conjugate; D013654:Taurine; D014580:Ursodeoxycholic Acid; D005947:Glucose