Project description:The tissue-specific packaging of the genome into the nucleus through chromatin is fundamentally involved in gene regulation, and aberrant modifications to chromatin are a hallmark of many diseases. We show here that a high fat (HF) diet leads to substantial chromatin remodeling in the livers of C57BL/6J mice, as compared to mice fed a control diet. Regions of the genome that display the greatest variation in chromatin accessibility between HF and control regions are targeted by transcription factors with known roles in the liver including HNF4α, CEBP/α, and FOXA1. Whereas livers of DBA/2J mice fed a HF or control diet also demonstrate diet-induced chromatin remodeling, the regions displaying the greatest variation are largely distinct from those observed in B6 livers, indicating a crosstalk between genetic and epigenetic components in determining how diet-induced chromatin remodeling is associated with metabolic disease progression. Examination of chromatin remodeling with FAIRE-seq in livers of mice (C57BL/6J and DBA/2J) fed a high fat or control diet. Complemented with gene expression and H3K4me1 analyses
Project description:The tissue-specific packaging of the genome into the nucleus through chromatin is fundamentally involved in gene regulation, and aberrant modifications to chromatin are a hallmark of many diseases. We show here that a high fat (HF) diet leads to substantial chromatin remodeling in the livers of C57BL/6J mice, as compared to mice fed a control diet. Regions of the genome that display the greatest variation in chromatin accessibility between HF and control regions are targeted by transcription factors with known roles in the liver including HNF4α, CEBP/α, and FOXA1. Whereas livers of DBA/2J mice fed a HF or control diet also demonstrate diet-induced chromatin remodeling, the regions displaying the greatest variation are largely distinct from those observed in B6 livers, indicating a crosstalk between genetic and epigenetic components in determining how diet-induced chromatin remodeling is associated with metabolic disease progression.
Project description:To investigate the differences in microRNA expression profiles between fibrotic and normal livers, we performed microRNA microarrays for total RNA extracts isolated from mouse livers treated with carbontetrachloride (CCl4) or corn-oil for 10 weeks (n=3/group). MicroRNAs were considered to have significant differences in expression level when the expression difference showed more than two-fold change between the experimental and control groups at p<0.05. We found that 12 miRNAs were differentially expressed in CCl4-induced fibrotic liver.
Project description:To investigate the differences in microRNA expression profiles between fibrotic and normal livers, we performed microRNA microarrays for total RNA extracts isolated from mouse livers treated with carbontetrachloride (CCl4) or corn-oil for 10 weeks (n=3/group). MicroRNAs were considered to have significant differences in expression level when the expression difference showed more than two-fold change between the experimental and control groups at p<0.05. We found that 12 miRNAs were differentially expressed in CCl4-induced fibrotic liver. To induce chronic liver fibrosis, seven-week-old mice received 0.6 ml/kg body weight of carbon-tetrachloride (CCl4) dissolved in corn-oil by intraperitoneal (i.p.) injection, twice a week for 10 weeks (n=3). As a control, same number of mice was injected with equal volume of corn-oil for 10 weeks.
Project description:The impact of high fat diet on secreted milk small RNA transcriptome was studied by isolating total RNA from milk fat fraction collected on lactation day 10 from control diet fed (C; n=5; 10% fat; 7% sucrose; Research Diets #D12450J, Brunswick, NJ) and high fat diet fed (HF; n=4; Research Diets #D12492, 60% of total kcal energy is fat and match 7% of total kcal is sucrose; Brunswick, NJ) mice.
Project description:The aim of this study was to assess whether chronic treatment with RPV can modulate the progression of chronic liver disease, especially of non-alcoholic fatty liver disease (NAFLD), through a nutritional model in wild-type mice Mice were daily treated with RPV (p.o.) and fed with normal or high fat diet during 3 months to induce fatty liver disease
Project description:The ketogenic diet has been successful in promoting weight loss among patients that have struggled with weight gain. This is due to the cellular switch in metabolism that utilizes liver-derived ketone bodies for the primary energy source rather than glucose. Fatty acid transport protein 2 (FATP2) is highly expressed in liver, small intestine, and kidney where it functions in both the transport of exogenous long chain fatty acids (LCFA) and in the activation to CoA thioesters of very long chain fatty acids (VLCFA). We have completed a multi-omic study of FATP2-null (Fatp2-/-) mice maintained on a ketogenic diet (KD) or paired control diet (CD), with and without a 24-hour fast (KD-fasted and CD-fasted) to address the impact of deleting FATP2 under high-stress conditions. Control (wt/wt) and Fatp2-/- mice were maintained on their respective diets for 4-weeks. Afterwards, half the population was sacrificed while the remaining were fasted for 24-hours prior to sacrifice. We then performed paired-end RNA-sequencing on the whole liver tissue to investigate differential gene expression. The differentially expressed genes mapped to ontologies such as the metabolism of amino acids and derivatives, fatty acid metabolism, protein localization, and components of the immune system’s complement cascade, and were supported by the proteome and histological staining.
Project description:Analysis of gene expression profiles is an attractive method for discovering how animals respond to environmental challenges in nature. Compared to low altitudes, high altitudes are characterized by reduced partial pressures of oxygen (hypoxia) and cooler ambient temperatures To better understand how mammals cope with high altitudes, we trapped wild house mice (Mus musculus domesticus) from 3 populations in La Paz, Bolivia (3000 - 3600 m) and 3 populations in Lima, Peru (0 – 200 m). Affymetrix GeneChip® Mouse Genome 430 2.0 Arrays were use to measure mRNA abundance in the livers of these mice.