Project description:Investigating the transcriptional changes in mouse livers exposed to low and high fat diets for 11 weeks. Determine what gene changes in the Cyp1b1 null livers may be contributing to prevention of increased adiposity when givin a high fat diet. Three Comparison experiment. Comparing wild-type low fat vs Cyp1b1 null low fat, wild-type high fat vs Cyp1b1 null high fat and low fat vs high in wild-type mice. Sample size is 3 per group. Limma analysis data provided in Series supplementary file (Normalized log2 ratio of (Cy3/Cy5) representing test group/control group).
Project description:Investigating the transcriptional changes in mouse livers exposed to low and high fat diets for 11 weeks. Determine what gene changes in the Cyp1b1 null livers may be contributing to prevention of increased adiposity when givin a high fat diet.
Project description:Wild type C57Bl/6J, Cyp1b1-null, and a substrain of Cyp1b1-null that are resistant to diet-induced obesity (Resistant Cyp1b1-null) timed mated pregnant dams were administered either a defined vitamin A sufficient diet or matched vitamin A deficient diet from embryonic day 4.5. Offspring liver gene expression was examined at birth (post-natal day 0) and at weaning (post-natal day 21).
Project description:This study sought to interrogate the effects of lipids and lipid metabolites on the hepatic proteome. Protein expression in high-fat diet (HFD) mouse livers vs. livers of normal chow fed (NC) mice were investigated using multiplexed quantitative LC-MS/MS (TMT labeling). This experiment contains additional replicates for normal chow and mice on high-fat diet for 16 weeks.
Project description:Hepatic fat accumulation has been widely associated with diabetes and hepatocellular carcinoma (HCC). Here, we aim to characterize the metabolic response that high fat availability elicits in livers prior to development of these diseases. We find that, after a short term on high fat diet, otherwise healthy mice show elevated hepatic glucose metabolization, activated glucose uptake, glycolysis and glucose contribution to serine as well as elevated pyruvate carboxylase activity compared to control diet mice. To understand other changes in the liver tissue after high fat diet exposure, we conducted untargeted transcriptomics and proteomics. This glucose phenotype occurred independent from transcriptional or proteomic programming, which identified increased peroxisomal and lipid metabolism pathways. Interestingly, we observe that high fat diet fed mice exhibit an increased lactate production when challenged with glucose. This trait seems to find a parallel in a human cohort, where we observe a correlation between waist circumference and lactate secretion after an oral glucose bolus across healthy individuals. In an in vitro model of hepatoma cells, we found physiologically relevant palmitate exposure stimulated production of reactive oxygen species (ROS) and glucose uptake, a similar glycolytic phenotype to the in vivo study. This effect is inhibited upon interference with peroxisomal lipid metabolism and ROS production. Furthermore, we find that with exposure to an HCC-inducing hepatic carcinogen, continuation of high fat diet enhances the formation of HCC (100% with resectable tumors) as compared to control (50% with resectable tumors) in mice. However, regardless of the dietary background, all murine tumors showed similar alterations in glucose metabolism compared to those identified in fat exposed non-transformed mouse livers. Further, the presence of tumors in high fat diet exposed mice normalized glucose tolerance. Lipidomics analysis of tumor tissue and liver tissue from high fat diet exposed mice identified tumor tissue enrichment of diacylglycerol (DG) and phosphatidylcholine (PC) species. Some of these species were also increased in high fat diet liver tissue compared to control diet liver tissue. These findings suggest that fat can induce similar metabolic changes in non-transformed liver cells than found in HCC, and that peroxisomal metabolism of lipids may be a factor in driving a glycolytic metabolism In conclusion, we show that normal, non-transformed livers respond to fat by inducing glucose metabolism.
Project description:Gene Set Enrichment Analysis of PEDF knockout livers revealed induction of pathways associated with experimental and human HCC and a transcriptional profile characterized by Wnt/β-catenin activation Genome-wide expression analysis of liver tissue of wild type vs PEDF knockout animals fed high fat diet
Project description:Purpose: RNAseq analyses were conducted to screen for the genes undergoing transcriptional changes either in the liver of high-fat-diet (HFD)-induced obese mice or in the liver of Lepr-deficient db/db mice compared to the livers of the respective control mice Methods: C57BL/6 wild-type male mice were fed on high-fat diet (HFD) or a low-fat diet (NCD) for 18 weeks starting from 6 weeks of age, and the livers were collected at 24 weeks of age at ad libitum-fed condition.Misty/misty or db/db were sacrificed at ad libitum-fed condition at 10weeks and the liver was collected. Results: 2079 genes and 1085 genes were identified in high-fat-diet fed mice and db/db mice, respectively.
Project description:Gene expression for genes differentially expressed between early vs. late tumor onset and high fat diet (HFD) vs. low fat diet (LFD) in mice.
