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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Liver gene expression profile _ wild type_ CYP7A1 transgenic

ABSTRACT: Bile acids are not only physiological detergents facilitating nutrient absorption, but also signaling molecules regulating metabolic homeostasis. We reported recently that transgenic expression of CYP7A1 in mice stimulated bile acid synthesis and prevented Western diet-induced obesity, insulin resistance and hepatic steatosis. The aim of this experiment is to determine the impact of induction of hepatic bile acid synthesis on liver metabolism by determining hepatic gene expression profile in CYP7A1 transgenic mice. CYP7A1 transgenic mice and wild type control mice were fed either standard chow diet or high fat high cholesterol Western diet for 4 month. Hepatic gene expressions were measured by microarray analysis. Our results indicate that hepatic bile acid synthesis is closely linked to cholesterogenesis and lipogenesis, and maintaining bile acid homeostasis is improtant in hepatic metabolic homeostasis. Male aged matched (~ 12-14 weeks) CYP7A1 transgenic mice and their wild type control littermates were fed a standard chow diet or a high fat (42%) high cholesterol (0.2%) diet (Harlan Teklad #88137) for 4 month Four groups (4 mice/group) are included in the experiments: Group 1: WT _ Chow Group 2: CYP7A1-tg + chow Group 3: WT + Western diet Group 4: CYP7A1-tg _ Western diet Total liver mRNA was isolated with a RNeasy kit (Qiagen) and used for microarray analysis.

ORGANISM(S): Mus musculus

SUBMITTER: John Chiang

PROVIDER: E-GEOD-38872 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Liver gene expression profile _ wild type_ CYP7A1 transgenic

Project description:Bile acids are not only physiological detergents facilitating nutrient absorption, but also signaling molecules regulating metabolic homeostasis. We reported recently that transgenic expression of CYP7A1 in mice stimulated bile acid synthesis and prevented Western diet-induced obesity, insulin resistance and hepatic steatosis. The aim of this experiment is to determine the impact of induction of hepatic bile acid synthesis on liver metabolism by determining hepatic gene expression profile in CYP7A1 transgenic mice. CYP7A1 transgenic mice and wild type control mice were fed either standard chow diet or high fat high cholesterol Western diet for 4 month. Hepatic gene expressions were measured by microarray analysis. Our results indicate that hepatic bile acid synthesis is closely linked to cholesterogenesis and lipogenesis, and maintaining bile acid homeostasis is improtant in hepatic metabolic homeostasis.

2013-08-15 | GSE38872 | GEO

Global hepatic transcript data from fasted male BXD strains on chow or high fat diet

Project description:Transcript data from livers from fasted-state BXD strains on chow or high fat diet We used microarrays to compare the hepatic expression differences across the BXD strain family and across two diverse diets 29-week-old male mice were fasted overnight (6pm-9am), anesthetized under isoflurane, and perfused, then livers were snap-frozen in liquid nitrogen for RNA extraction and RNEasy cleanup. Each dietary and strain cohort consisted of ~5 animals which were prepared independently then pooled evenly by M-BM-5g RNA before the Affymetrix arrays were run.

2014-09-11 | E-GEOD-60149 | biostudies-arrayexpress

Global brown adipose transcript data from fasted male BXD strains on chow diet

Project description:Transcript data from brown adipose tissue from fasted-state male BXD strains on chow or high fat diet We used microarrays to compare the brown adipose expression differences across males from the BXD strain family and across two diverse diets 29-week-old male mice were fasted overnight (6pm-9am), anesthetized under isoflurane, and perfused, then brown adipose tissue was snap-frozen in liquid nitrogen for RNA extraction and RNEasy cleanup. Each dietary and strain cohort consisted of ~5 animals which were prepared independently then pooled evenly by M-BM-5g RNA before the Affymetrix arrays were run.

2014-09-26 | E-GEOD-60150 | biostudies-arrayexpress

Global quadriceps skeletal muscle transcript data from fasted male BXD strains on chow or high fat diet

Project description:Transcript data from quadriceps skeletal muscle from fasted-state male BXD strains on Quadriceps, Chow or Quadriceps, High fat diet We used microarrays to compare the skeletal muscle expression differences across males in the BXD strain family and across two diverse diets 29-week-old male mice were fasted overnight (6pm-9am), anesthetized under isoflurane, and perfused, then quadriceps were snap-frozen in liquid nitrogen for RNA extraction and RNEasy cleanup. Each dietary and strain cohort consisted of ~5 animals which were prepared independently then pooled evenly by M-BM-5g RNA before the Affymetrix arrays were run.

2014-09-26 | E-GEOD-60151 | biostudies-arrayexpress

The Microbial Metabolite Deoxycholic Acid Modulates Cholesterol Metabolism in the Germ-Free Mouse

Project description:Deoxycholic acid (DCA) is a secondary bile acid produced by a small number of commensal species of bacteria present in the mammalian gut. Elevated DCA concentration correlates with disease states including colon cancer and cholesterol gallstones, but the associated mechanisms are not fully understood. Both primary and secondary bile acids are also capable of affecting gene expression through nuclear receptors such as FXR. To better understand the impact of a commensal-derived secondary bile acid on host metabolism we fed DCA to germ-free (GF) mice, which normally lack DCA, and compared the hepatic transcriptomes of bile acid fed GF mice to GF mice receiving a control diet, as well as to those of conventionally housed control animals. Interestingly, the feeding of DCA to GF mice, but not the feeding of cholic acid (CA) from which DCA is derived, results in an up-regulation of genes of cholesterol biosynthetic pathways. GF mice normally have elevated hepatic cholesterol compared to conventionally housed mice. Despite increase in the expression of cholesterol biosynthetic genes, the DCA fed GF mice showed a markedly decreased level of hepatic cholesterol equivalent to the hepatic cholesterol concentration of conventionally colonized animals. Total cholesterol in the serum was unaffected by DCA, but there was a decrease in the HDL lipoprotein fraction as well as an increase in the non-HDL lipoprotein fraction of the serum cholesterol. DCA, but not CA, is sufficient to modulate host lipoprotein metabolism. Taken together, these results suggests that a minor component of the gut microbiome has a significant impact on cholesterol homeostasis through secondary metabolism of bile acids and suggests a possible therapeutic intervention route through the microbial metabolic pathways. two mouse strains, three diets, one time point

2015-01-08 | E-GEOD-34730 | biostudies-arrayexpress

Hepatic gene expression study

Project description:The aim of this study was to compare the effects of cocoa butter and safflower oil on hepatic transcript profiles, lipid metabolism and insulin sensitivity in healthy rats. Cocoa butter-based high-fat feeding for three days did not affect plasma total triglyceride (TG) levels or TG-rich VLDL particles or hepatic insulin sensitivity, but changes in hepatic gene expression were induced that might lead to increased lipid synthesis, lipotoxicity, inflammation and insulin resistance if maintained. Safflower oil increased hepatic Î²-oxidation, was beneficial in terms of circulating TG-rich VLDL particles, but led to reduced hepatic insulin sensitivity. The effects of safflower oil on hepatic gene expression were partly overlapping with those exerted by cocoa butter, but fewer transcripts from anabolic pathways were altered. Increased hepatic cholesterol levels and increased expression of hepatic CYP7A1 and ABCG5 mRNA, important gene products in bile acid production and cholesterol excretion, were specific effects elicited by safflower oil only. Common effects on gene expression included increased levels of p8, DIG-1 IGFBP-1 and FGF21, and reduced levels of SCD-1 and SCD-2. This indicates that a lipid-induced program for hepatic lipid disposal and cell survival was induced by three days of high-fat feeding, independent on the lipid source. Based on the results, we speculate that hepatic TG infiltration leads to reduced expression of SCD-1, which might mediate either neutral, beneficial or unfavourable effects on hepatic metabolism upon high-fat feeding, depending on which fatty acids were provided by the diet. Keywords: Hepatic gene expression Two-condition experiment. Biological replicates: 4 male rat livers from rats on a standard diet, 4 male rat livers from rats on a cocoa butter diet, 4 male rat livers from rats on a high-fat (safflower oil) diet. One replicate per array.

2010-05-18 | E-GEOD-13936 | biostudies-arrayexpress

Microarray analysis of mouse cerebral cortex from brain-specific Bmal1 knockout and Per1;Per2 double mutant mice at 2 timepoints

Project description:The aim of this study was to examine the effect of genetic disruption of the circadian clock on gene expression in the cortex across timepoints. Circadian clock protein regulate many critical aspects of cellular function, and Bmal1 knockout mice develop severe neuroinflammation, suggesting a role for circadian clock gene in brain homeostatic function. We compared brain-specific Bmal1 KO mice (Nestin-Cre;Bmal1(flox/flox) with Per1/2 double mutant mice, in order to assess the effects of deletion of the positive and negative limbs of the core clock. 11mo Cre-, NestinCre+/-;Bmal1(fx/fx), or Per1brdm,Per2brdm mice were entrained to 12h light:dark conditions with lights on at 6am for one month, then placed in constant darkness for 24 hours, after which mice were harvested at 6am (CT6) or 6pm (CT18), still in the dark. Mice were anesthetized in the dark, then perfused briefly with PBS+heparin. The brain was then quickly dissected on a cold surface, and the cerebral cortex flash frozen in liquid nitrogen. Cortex samples were mechanically dissociated with a Qiashredder device, then extracted with chloroform and diluted in 70% ethanol. RNA was extracted using Qiagen RNEasy kit according to manufacturers specifications. cDNAs were chemically labeled with Kreatech ULS RNA labeling kit (Kreatech Diagnostics) and Cy5-labeled cDNAs were hybridized to Agilent Mouse v2 4x44K microarrays (G4846A-026655).

2018-09-11 | E-MTAB-7151 | biostudies-arrayexpress

Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism

Project description:Accumulation of excess nutrients hampers proper liver function and is linked to non-alcoholic fatty liver disease (NAFLD) in obesity. However, the signals responsible for an impaired adaptation of hepatocytes to obesogenic dietary cues remain still largely unknown. Post-translational modification by the Small Ubiquitin-like Modifier (SUMO), allows for adynamic regulation of numerous processes including transcriptional reprograming. We demonstrate that specific SUMOylation of transcription factor Prox1 represents a nutrient-sensitive determinant of hepatic fasting metabolism. Prox1 was highly SUMOylated on lysine 556 in the liver of ad libitum and re-fed mice, while this modification was abolished upon fasting. In the context of diet-induced obesity, Prox1 SUMOylation became less sensitive to fasting cues. The hepatocyte-selective knock-in of a SUMOylation-deficient Prox1 mutant into mice fed a high-fat/high-fructose diet led to a reduction of systemic cholesterol levels, associated with the induction of liver bile acid detoxifying pathways during fasting. The generation of tools to maintain the nutrient-sensitive SUMO-switch on Prox1 may thus contribute to the development of “fasting-based” approaches for the preservation of metabolic health.

2023-10-24 | PXD041329 | Pride

MAFG is a transcriptional repressor of bile acid synthesis and metabolism (ChIP-seq)

Project description:Specific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR.

2016-02-04 | GSE77529 | GEO

Differential gene expression following MafG overexpression

2016-02-04 | GSE77507 | GEO

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