Project description:To investigate the molecular basis for male-specific steatohepatitis in Lamin A/C-deficient livers, microarray gene expression analysis was performed on total liver RNA isolated from 26- to 39-week-old, male LMNA+/+, LMNA flx/+, and LMNA flx/flx; Alb-Cre+ C57BL/6 mice fed either normal chow (NC) or high fat diet plus carbohydrate-supplemented water (HFD). Lamins are nuclear intermediate filament proteins that comprise the major components of the nuclear lamina in metazoan cells. Mutations in LMNA, which encodes lamins A/C, cause diseases termed laminopathies, including lipodystrophy, cardiomyopathy, and premature aging. The lamin A/C mutation-associated Dunnigan familial partial lipodystrophy is typically accompanied by fatty liver disease. The role of lamins in the liver is unknown, and it is unclear whether laminopathy-associated liver disease is due to primary hepatocyte defects or systemic alterations. To address these questions, mice carrying a hepatocyte-specific deletion of Lmna (KO mice) were generated. KO hepatocytes manifested abnormal nuclear morphology, and KO mice developed spontaneous male-selective hepatosteatosis, with increased susceptibility to high fat diet-induced steatohepatitis and fibrosis. The molecular mechanism by which liver-specific Lamin A/C deficiency induces male-specific steatohepatitis is unknown. The microarray data presented here demonstrates that hepatic Lmna deficiency is associated with upregulated expression of fatty acid transporters, lipid biosynthetic enzymes, lipid-droplet associated proteins, and interferon-regulated genes and other pro-inflammatory mediators.
Project description:RNA-sequening of livers from male and female C57BL/6J mice fed either chow diet or chow diet + simvastatin (0.1g/kg body weight) for 4 weeks.
Project description:To investigate the role of hepatic Pck1 in diet-induced nonalcoholic steatohepatitis (NASH), liver-specific Pck1-knockout mice were developed with Alb-Cre. Wild-type (WT) and Pck1-cKO mice were fed a Chow diet (Research Diets, D12450J: 10% Kcal fat, with tap water) or NASH-inducing diet (Research Diets, D12492: 60% Kcal fat, with drinking water containig 23.1 g/L fructose and 18.9 g/L glucose) for 24 weeks. RNA was extracted from the livers of mice from all treatment groups and used for RNA seqencing. RNA-seq data demonstrated that gluconeogenic enzyme PCK1 deficiency played an important role in the development of NASH.
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.
Project description:The present study aimed to examine the effect of high-fat diet prior to pregnancy on the liver of mouse offspring. Female C57BL/6J mice were fed a normal chow (15.2% fat by energy) (CTR and CTR-PP groups) or a high-fat chow (31.2% fat by energy) (HFD and HFD-PP groups) for 3−4 weeks and then mated with male C57BL/6J mice fed normal chow. Some mothers continued on the same diet until pups reached 21 days of age (CTR and HFD), and others were fed the different chows from gestational day 0 (CTR-PP and HFD-PP) to determine the effects of a high-fat diet during the pre-pregnancy period in HFD-PP/CTR and HFD/CTR-PP comparisons.
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:Male C57Bl/6J mice were fed 45%kcal fat diet (HF) or regular rodent chow (NC) from 4 weeks to 16 weeks of age. Gene expression was compared between RNA obtained from pancreatic islets of HF fed mice and NC mice.
Project description:Gene expression in livers of male wild-type (WT) and OGG1-deficient (Ogg1-/-) mice fed either a chow diet or a high-fat diet (HFD) were examined. Mice were fed the diet for 10 weeks prior to tissue collection and were 22 weeks of age at the time of tissue collection.
Project description:RNA sequencing of mouse lung endothelial cells from male wildtype (TET2fl/fl Cre negative, tamoxifen-injected) or endothelial-specific TET2 knockout mice (TET2fl/fl, Cdh5-CreERT2 positive, tamoxifen-injected) fed either a standard chow diet or a high fat diet for 20 weeks.
Project description:In this study we sought to determine how hepatocyte-specific PPARgamma expression regulates hepatic gene expression in normal (healthy) mice fed a LFCF diet, or mice that were fed a HFCF diet for 24 weeks to induce non-alcoholic steatohepatitis (NASH). Specifically, we used chow-fed adult (10 week-old) PPARgamma floxed male mice and injected them with AAV8-TBG-Cre to knockout PPARgamma in hepatocytes (KO). A subset of PPARgamma floxed mice were injected with AAV8-TBG-Null to generate controls (C). Two weeks after AAV injections, half of the mice in each group were fed a low fat, cholesterol and fructose (LFCF) diet, or a high fat, cholesterol and fructose (HFCF) diet for 24 weeks. Livers were collected at the end of the study to assess hepatic gene expression with RNA-seq (performed by Novogen, Inc.)
