Changes in Hepatic Gene Expression upon Oral Administration of Taurine-Conjugated Ursodeoxycholic Acid in ob/ob Mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE22608 | GEO | 2010/12/31
SECONDARY ACCESSION(S): PRJNA128347
REPOSITORIES: GEO
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Project description:We 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.
2010-12-31 | E-GEOD-22608 | biostudies-arrayexpress
Project description: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.
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Project description:The purpose of this study was to identify leptin target genes and subsequent pathways correlated with leptin-mediated weight loss. We utilized the microarray technology to compare two types of leptin administration: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We report here the impact of central and peripheral administration of leptin on food intake, body weight and body fat composition in ob/ob mice. We also report hepatic gene expression changes caused by central versus peripheral leptin administration. Keywords: comparison Leptin deficient (ob/ob) mice were continuously administered leptin over 12-days using central (intracerebroventricular) or peripheral (subcutaneous) route of administration. Liver RNA was extracted and hybridized to Illumina microarrays and gene expression data was analyzed. The global gene expression profiles were compared after the central and peripheral leptin treatments in ob/ob mice and C57BL6 mice were used for the baseline gene expression.
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Project description:The purpose of this study was to identify leptin target genes and subsequent pathways correlated with leptin-mediated weight loss. We utilized the microarray technology to compare two types of leptin administration: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We report here the impact of central and peripheral administration of leptin on food intake, body weight and body fat composition in ob/ob mice. We also report hepatic gene expression changes caused by central versus peripheral leptin administration. Keywords: comparison
2010-11-10 | GSE20878 | GEO
Project description:To test whether NDGA attenuate dyslipidemia and hepatic steatosis by enhancing fatty acid oxidation through activation of PPAR-α. Using wild type (WT, C57BL/6) fed with chow diet as control, WT mice were either fed with high-fat diet or high-fat diet with NDGA (2.5g/kg food); ob/ob mice were fed with either chow or chow with NDGA (2.5 g/kg food), and maintained on the respective diets for 16 weeks. The expression of lipid metabolism related genes in the liver of these mice were analyzed using Phalanx GPL6845 platform (Mouse OneArray V1). Together with other biochemical/physiological data, our results suggest that the beneficial actions of NDGA on dyslipidemia and hepatic steatosis in ob/ob mice are exerted primarily through enhanced fatty acid oxidation and energy utilization via the activation of PPAR- α receptor activity.
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Project description:To identify novel transcriptional factors involved in dysfunctional hepatic lipids homeostasis in obesity, mRNA microarray analysis were performed to of livers of ob/ob mice, a widely used obese model, and C57BL/6J control mice. Chow-fed ob/ob and C57BL/6J mice were housed in a 12 h of light and 12 h of dark cycle and fed ad libitum a regular chow diet. Mice were sacrificed at 16:00 (Zeitgeber Time 8 during light phase). Total RNA was prepared from each liver using TRIzol (Invitrogen). Equal aliquots of total RNA from each of four mouse livers in each group were pooled and used for biotin labeling as described in the Affymetrix technical bulletin. Then the transcriptional profiles of samples were probed using the Gene-Chip Mouse Genome 430 2.0 arrays.
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