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Hepatic transcriptome profiling of liver-specific Xbp1 knockout mice fed a high fat diet

ABSTRACT: Xbp1 is an important regulator of unfolded protein response and lipid metabolism. Its dyregulation has been associcated in human NASH. Feeding a high fat diet with fructose/sucrose to mice causes progressive, fibrosing steatohepatitis. This study is to use RNA-Seq to identify differentially expressed genes in hepatic Xbp1 deficient mice livers fed with a high fat diet compared to controls. Hepatic Xbp1 deficient mice or flox controls were fed either regular chow or a high fat diet (n=4). Samples from each cohort were pooled into two replicates.

ORGANISM(S): Mus musculus

SUBMITTER: Richard Green

PROVIDER: E-GEOD-64824 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Hepatocyte X-box binding protein 1 deficiency increases liver injury in mice fed a high-fat/sugar diet.

Liu Xiaoying X Henkel Anne S AS LeCuyer Brian E BE Schipma Matthew J MJ Anderson Kristy A KA Green Richard M RM

American journal of physiology. Gastrointestinal and liver physiology 20151015 12

Fatty liver is associated with endoplasmic reticulum stress and activation of the hepatic unfolded protein response (UPR). Reduced hepatic expression of the UPR regulator X-box binding protein 1 spliced (XBP1s) is associated with human nonalcoholic steatohepatitis (NASH), and feeding mice a high-fat diet with fructose/sucrose causes progressive, fibrosing steatohepatitis. This study examines the role of XBP1 in nonalcoholic fatty liver injury and fatty acid-induced cell injury. Hepatocyte-specif ...[more]

PMID: 26472223

Similar Datasets

Hepatic transcriptome profiling of liver-specific Xbp1 knockout mice fed a high fat diet

Project description:Xbp1 is an important regulator of unfolded protein response and lipid metabolism. Its dyregulation has been associcated in human NASH. Feeding a high fat diet with fructose/sucrose to mice causes progressive, fibrosing steatohepatitis. This study is to use RNA-Seq to identify differentially expressed genes in hepatic Xbp1 deficient mice livers fed with a high fat diet compared to controls.

2016-01-07 | GSE64824 | GEO

Rat Liver HFD vs Chow, HFD vs PKCepsilon ASO

Project description:Insulin resistance drives the development of type 2 diabetes (T2D). In liver, diacylglycerol (DAG) is a key mediator of lipid-induced insulin resistance. DAG activates protein kinase C epsilon (PKCÎµ), which phosphorylates and inhibits the insulin receptor. In rats, a 3-day high fat diet produces hepatic insulin resistance through this mechanism, and knockdown of hepatic PKCÎµ protects against high fat diet-induced hepatic insulin resistance. Here we employ a systems level approach to uncover additional signaling pathways involved in high fat diet-induced hepatic insulin resistance. We used quantitative phosphoproteomics to map global in vivo changes in hepatic protein phosphorylation in chow-fed, high fat-fed, and high fat-fed with PKCÎµ knockdown rats to distinguish the impact of lipid- and PKCÎµ-induced protein phosphorylation.

2018-08-30 | PXD010209 | Pride

Genome-wide expression profile of livers from mice fed HFD,SO-HFD or Viv chow [RNAseq]

Project description:Purpose: Aim of the study is to identify changes in hepatic gene expression induced by either a 40kcal% coconut oil rich high fat diet (HFD), a 40kcal% soybean oil plus coconut oil high fat diet (SO-HFD) or a low fat vivarium chow diet (Viv). Methods: Livers from mice that had been fed one of the above mentioned diets for 35 weeks, were used to make cDNA libraries that were then sent for deep sequencing, using the Illumina TruSeq RNA. Result: Many genes involved in metabolism, lipid binding, transport and storage and many Cyp genes are dysregulated in the two high fat diets as compared to Viv HFDs in SO-HFD mice. Comparing the two HFDs shows more metabolism and disease related genes dysregulated in SO-HFD vs HFD. Conclusion: A diet high in soybean oil may be more detrimental to metabolic health than a diet high in saturated fats. cDNA isolated from livers from mice fed HFD, SO-HFD or Viv for 35 weeks, were 50bp pair-ended sequenced in triplicate using Illumina TruSeq RNA Sample Prep v2 Kit.

2015-08-28 | E-GEOD-68360 | biostudies-arrayexpress

Transcriptome analyses of skeletal muscle in αB-crystallin/HspB2 knockout and wild-type mice on a normal or high fat diet

Project description:We profiled the skeletal muscle transcriptome between wild type and αB-crystallin/HspB2 knock mice exposed to normal chow and high fat diets to examine the role of αB-crystallin/HspB2 in diet induced obesity. Combined with metabolic profiling of the mice, these data reveal that αB-crystallin/HspB2 is involved in the genesis of insulin resistance on a high fat diet, and we provide extensive RNA profiling to illuminate potential mechanistic insights into the muscle-specific role of αB-crystallin/HspB2. Hind limb muscle mRNA profiles of wild type and αB-crystallin/HspB2 knock mice exposed to either normal chow or high fat diets using RNAseq analysis

2015-09-01 | E-GEOD-66557 | biostudies-arrayexpress

Identification of eQTLs for Hepatic Xbp1s and Socs3 Gene Expression in Mice fed a High-Fat, High Caloric Diet

Project description:Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent form of hepatic disease and feeding mice a High-Fat, High-Caloric (HFHC) diet is a standard model of NAFLD. In order to better understand the genetic basis of NAFLD, we conducted an expression quantitative trait locus (eQTL) analysis of mice fed a HFHC diet. 265 (A/J × C57BL/6J) F2 male mice were fed a HFHC diet for 8 weeks. QTL analysis was utilized to identify genomic regions that regulate hepatic gene expression of Xbp1s and Socs3. We identified two overlapping loci for Xbp1 and Socs3 on Chr 1 (164.0-185.4 Mb and 174.4-190.5 Mb, respectively) and Chr 11 (41.1-73.1 Mb and 44.0-68.6 Mb, respectively), and an additional locus for Socs3 on Chr 12 (109.9-117.4 Mb). C57BL/6J-Chr 11A/J/ NaJ mice fed a HFHC diet manifested the A/J phenotype of increased Xbp1s and Socs3 gene expression (p<0.05), while C57BL/6J-Chr 1A/J/ NaJ mice retained the C57BL/6 phenotype. In addition, we replicated the eQTLs on Chr 1 and 12 (LOD scores ? 3.5) using mice from the BXD murine reference panel challenged with CCl4 to induce chronic liver injury and fibrosis. We have identified overlapping eQTLs for Xbp1 and Socs3 on Chr 1 and 11, and consomic mice confirmed that replacing the C57BL/6 with the A/J Chr 11 resulted in an A/J phenotype for Xbp1 and Socs3 gene expression. Identification of the genes for these eQTLs will lead to a better understanding of the genetic factors responsible for NAFLD and potentially other hepatic diseases. Liver samples from eight-week-old AJ and C57BL6J males fed a High Fat High Calorie diet.

2014-08-02 | E-GEOD-56987 | biostudies-arrayexpress

JNK-mediated control of gene expression in liver

Project description:RNAseq analysis of gene expression in Liver of Control and JNK deficient mice fed a control or a High fat diet Contro(Albcre+)l and mice with liver-specific defiency of JNK (Alb Cre+ Jnk1flox/flox, Jnk2flox/flox or Jnk1flox/floxJnk2flox/flox) were fed a control or a high fat diet for 16 weeks. Gene expression analysis in liver was analyzed by RNAseq

2015-03-06 | E-GEOD-55190 | biostudies-arrayexpress

Liver proteomic assessment of mice fed high carbohydrate and high fat diets identify a disconnect between proteins associated with de novo lipogenesis and fat

Project description:De novo lipogenesis (DNL) has been implicated in the development and progression of hepatic liver steatosis. Hepatic DNL is strongly influenced by dietary macronutrient composition with diets high in carbohydrate increasing DNL and diets high in fat decreasing DNL. The enzymes in the core DNL pathway have been well characterised however less is known about proteins that play accessory or regulatory roles in DNL. In the current study, we associate measured rates of hepatic DNL and liver fat content with abundance of liver proteins from liquid chromatography mass spectrometry in mice to identify known and uncharacterised proteins that may have a role in DNL. Male C57BL/6J mice were fed either a standard chow diet a semi-purified high starch diet or a high fat diet. Both semi-purified diets resulted in increased body weight, fat mass and liver triglyceride content compared to chow-fed mice while hepatic DNL was increased in the high starch fed mice and decreased in the high fat fed mice. Proteomic analysis was carried out on the livers of these mice and proteins were identified that associated with either the rate of DNL or triglyceride content in the liver. There was no overlap between DNL and triglyceride associated proteins. We identify novel proteins associated with DNL that are involved in taurine metabolism, which suggests a link between these pathways. Further analysis identified proteins that are differentially regulated when comparing a non-purified chow diet to either of the semi-purified diets to provide a set of proteins that are regulated by the degree of dietary complexity alone. Finally, we compared the liver proteome between 4 week-fed and 30-week diet-fed mice and found remarkable similarity suggesting that the majority of diet-regulated proteins change early in response to differing dietary components.

2024-10-30 | PXD054323 | Pride

Hepatic transcriptome changes in testosterone-deficient pigs fed a high-fat diet

Project description:To gain insight into the role of testosterone in modulating hepatic fat accumulation, we collected liver tissues from high fat diet-fed intact male pigs, castrated male pigs, and castrated male pigs with testosterone replacement. RNA-Seq was employed to profile hepatic gene expression in pigs with different testosterone levels. Liver mRNA profiles of intact male pigs fed a HFC diet, castrated male pigs fed a HFC diet, and castrated male pigs treated with testosterone fed a HFC diet were generated by deep sequencing, using Illumina HiSeq 2000.

2015-01-08 | E-GEOD-62696 | biostudies-arrayexpress

Mus musculus

Project description:Hepatic transcriptome profiling of liver-specific Xbp1 knockout mice fed a high fat diet

| PRJNA271953 | ENA

Liver tissue HELP-tagging cytosine methylation data from C57BL/6J mice receiving high-fat diet with or without lingonberries

Project description:The C57BL/6J mouse model develops obesity and pre-diabetes when fed a high-fat diet. In this experiment, DNA methylation was assessed globally at specific CpG sites in liver tissue from mice receiving high-fat diet (45E% from fat) for 13 weeks (Control) or high-fat diet supplemented with 20% (w/w) of freeze-dried lingonberries (n=4). Our findings show that lingonberries prevent development of high-fat induced obesity, hepatic steatosis and low-grade inflammation, and the DNA was hypermethylated in mice receiving lingonberries compared to control. Genome wide hepatic DNA methylation comparison between mice fed high-fat diet with or without a lingonberry supplement (n=4/group).

2015-09-20 | E-GEOD-67277 | biostudies-arrayexpress

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