Project description:To assess the effect of steatosis and oxidative stress on progression of liver fibrosis, we have employed whole genome microarray expression profiling as a discovery platform to identify genes that are related with oxidative stress- and steatosis-induced hepatic fibrogenesis. When wild type mice were fed high-fat/high-sucrose diet for 24 weeks, expression of 69 genes was changed more than 10-fold compared with wild type animals fed normal diet, 11 of which were categorized to lipid metabolic process. Moreover, expression of 208 genes showed more than 5-fold changes in Tet-mev-1 mice fed high-fat/high-sucrose diet compared with the same transgenic animals fed normal diet, and gene ontology analyses indicated significant changes in chemokine activity and chemokine receptor binding as well as defense and immune responses. oxidative stress and high fat high calorie induced gene expression in wild type or Tet-mev-1 mouse liver tissue. wild type and Tet-mev-1 mice were fed either normal diet or high fat high sucrose diet for 4 months, and have been given doxycycline-containing water from embryo. Each group were perfomed by duplicate.
Project description:To assess the effect of steatosis and oxidative stress on progression of liver fibrosis, we have employed whole genome microarray expression profiling as a discovery platform to identify genes that are related with oxidative stress- and steatosis-induced hepatic fibrogenesis. When wild type mice were fed high-fat/high-sucrose diet for 24 weeks, expression of 69 genes was changed more than 10-fold compared with wild type animals fed normal diet, 11 of which were categorized to lipid metabolic process. Moreover, expression of 208 genes showed more than 5-fold changes in Tet-mev-1 mice fed high-fat/high-sucrose diet compared with the same transgenic animals fed normal diet, and gene ontology analyses indicated significant changes in chemokine activity and chemokine receptor binding as well as defense and immune responses.
Project description:Type 2 diabetic cardiomyopathy (DCM) has been linked to Ca2+ signaling alterations, notably a decreased mitochondrial Ca2+ uptake. Uncovering of Ca2+ microdomains between cardiac mitochondria and reticulum launched a new investigation avenue for cardiometabolic diseases. We here aimed to study if the impairment of mitochondrial Ca2+ handling could be due to a dysregulation of the reticulum-mitochondria interactions or of the mitochondrial Ca2+ uniporter in the diabetic mice heart. Phenotypic alterations of the type 2 diabetic mouse heart, was done using an in vivo obesogenic high fat high sucrose diet fed mouse model (HFHSD: 20% proteins, 36% lipids). The composition of the cardiac MAM fractions between standard diet-fed (SD) mice and HFHSD (HF) mice at 16 weeks was analysed by MS-based quantitative proteomics.
Project description:We have employed whole genome microarray expression profiling in the liver of mice fed a high-fat, high-sucrose diet for 15 weeks to search genes with N-terminal signal sequences whose expression is altered concomitantly with changes in islet size. At 15 weeks, this analysis revealed a significant >4-fold upregulation in 118 genes and downregulation by >75% in 22 genes encoding putative secreted factors in liver of mice fed a HFHS, although few changes (<2-fold upregulated or >one-half downregulated) were observed at 10 weeks. Expression of four genes (NRG1, GPNMB, SERPINB1 and HGF) from this signature was quantified in the different RNA samples by real-time PCR, confirming low variability between mice.
Project description:Identify genes in the liver whose expression is under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP). The HMDP comprises classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Parks et al Cell Metabolism 2015. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness. GWAS for expression of liver in inbred strains fed chow diet for 8 weeks followed by high-fat/high-sucrose diet 8 weeks
Project description:In the experiment two groups of rats were compared. The control group consisted of 10 male, 5- to 6-weeks old, Fischer 344 (F344) rats (Nossan, Correzzana, Milan, Italy) fed a high fat, high sucrose, low fibre diet (control diet) for two weeks. This diet was based on the AIN76 diet [19], and was modified to contain 23% (w/w) fat (from corn oil) and a low level of cellulose (2% w/w), to mimic the high risk of colon cancer in human populations consuming high fat diets. The experimental group consisted of 10 male, 4- to 5-weeks old, F344 rats fed the same high fat diet as the control group in combination with 50 mg/kg red wine polyphenols for two weeks. The red wine polyphenol extract was prepared as described by Femia et al.<br> Total RNA was extracted using the RNeasy Midi kit (Qiagen, Milan, Italy). Equally amounts of RNA extracted from the colon mucosa of control diet-fed rats (n=10) were pooled and used as common reference for all hybridizations.
Project description:Identify genes in the skeletal muscle whose expression is under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP). The HMDP comprises classical inbred and recombinant inbred wild type mice. The neqc-normalized values of genes were used for genome wide association. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness. GWAS for expression of skeletal muscle in inbred strains fed chow diet for 8 weeks followed by high-fat/high-sucrose diet 8 weeks
Project description:In order to study the heart disorder that the long term, high energy diet caused, Bama miniature pigs were fed a high-fat, high-sucrose diet for 23 months. These pigs developed symptoms of metabolic syndrome and showed cardiac steatosis and hypertrophy with a greatly increased heart weight (1.82-fold, P<0.05) and heart volume (1.60-fold, P<0.05) compared with the control pigs. To understand the molecular mechanisms of cardiac steatosis and hypertrophy, nine pig heart cRNA samples were hybridized to porcine GeneChips.
Project description:Publication Title: DNA methylation alters transcriptional rates of differentially expressed genes and contributes to pathophysiology in mice fed a high fat diet. It is now well established that an intrauterine environment altered by overnutrition or malnutrition can change gene expression patterns through epigenetic mechanisms that may persist through generations. However, it is less clear if overnutrition alters epigenetic control of gene expression in adults, or if whether such mechanisms contribute to the pathology of obesity. Here we test the hypothesis that exposure to a high fat diet alters hepatic DNA methylation and gene expression patterns, and explore the contribution of such changes to the pathophysiology of overnutrition. RNA-seq and targeted high-throughput bisulfite DNA sequencing were used to undertake a systematic analysis of the hepatic response to a high fat diet. A subset of genes was found whose expression levels were altered in concert with DNA methylation changes. Using chromatin immunoprecipitation of RNA polymerase, we determined that hypermethylation correlated with decreased transcription of two of the genes, Phlda1 and Onecut1. A subnetwork of these genes and their nearest neighbors was generated from an existing Bayesian gene network that contained numerous hepatic regulatory genes involved in lipid and body weight homeostasis. Hepatic-specific depletion of Phlda1 in mice decreased the genes in the subnetwork, and led to increased oil droplet size in standard chow-fed mice, an early indicator of steatosis, validating the contribution of this gene to the phenotype.
Project description:In order to study the heart disorder that the long term, high energy diet caused, Bama miniature pigs were fed a high-fat, high-sucrose diet for 23 months. These pigs developed symptoms of metabolic syndrome and showed cardiac steatosis and hypertrophy with a greatly increased heart weight (1.82-fold, P<0.05) and heart volume (1.60-fold, P<0.05) compared with the control pigs. To understand the molecular mechanisms of cardiac steatosis and hypertrophy, nine pig heart cRNA samples were hybridized to porcine GeneChips. The control group consisted of 6 Bama pigs fed a control diet, and the HFHSD group comprised 6 pigs that were induced with a HFHS diet, which included 37% sucrose, 53% control diet and 10% pork lard. The pigs were fed twice every day and provided water ad libitum for 23 months. The pigs were fasted for 12 hours and euthanized with ketamine and xylazine. Pig hearts from the HFHSD group pigs (120, 126, 138, 140, 144, and 146) and three control group pigs (157, 159, and 161) were sampled and preserved in liquid nitrogen and then for RNA extraction and hybridization on Affymetrix microarrays.