Project description:Male and female mice (Bl6/J) were fed a chow diet (control 1 and control 2) or a High fat diet (HFD) or a Choline deficient High fat diet (CD HFD) or a Western Diet (WD) or a Western Diet supplemented with glucose and fructose in drinking water (WD glucose fructose) for 15 weeks.
Project description:To determine the effect of consumption of a quercetin-rich diet on obesity and dysregulated hepatic gene expression, C56BL/6J mice were fed for 20 weeks on control or a Western diet high in fat, cholesterol and sucrose, both with or without 0.05% quercetin. Chronic dietary intake of quercetin reduced body weight gain and visceral and liver fat accumulation, and improved hyperglyceamia, hyperinsulinaemia, dyslipidaemia in mice fed a Western-style diet. Feeding a Western-style diet altered expression of genes related to inflammatory responses, lipid metabolism and oxidative phosphorylation in C57BL/6J mice after 20 weeks. The results from exhaustive gene expression analysis showed that quercetin minimally influenced hepatic gene expression in mice fed the Western diet. The gene screening results (GSEA) were consistent with the notion that it did improve mitochondrial function to some extent. Quantitative RT-PCR analysis indicated that quercetin did influence important regulators of fat accumulation and metabolic disorders. Our results suggest that quercetin reduces fat accumulation presumably through decreasing oxidative stress and increasing PPARα expression, and the following improvement of gene expression related to steatosis in the liver. C56BL/6J mice were fed for 20 weeks on AIN93G (con) or a Western diet high in fat, cholesterol and sucrose, both with or without 0.05% quercetin for 20 weeks.
Project description:Examination of gene expression profiles from liver of C57BL/6 mice and LDL receptor deficient mice fed on either a low fat diet or a high fat Western-style diet for 12 weeks. Three replicates of each condition analyzed. Keywords = LDL receptor deficiency, high fat diet, atherosclerosis, liver Keywords: repeat sample
Project description:Examination of gene expression profiles from liver of C57BL/6 mice and LDL receptor deficient mice fed on either a low fat diet or a high fat Western-style diet for 12 weeks. Three replicates of each condition analyzed. Keywords = LDL receptor deficiency, high fat diet, atherosclerosis, liver
Project description:To determine the effect of consumption of a quercetin-rich diet on obesity and dysregulated hepatic gene expression, C56BL/6J mice were fed for 20 weeks on control or a Western diet high in fat, cholesterol and sucrose, both with or without 0.05% quercetin. Chronic dietary intake of quercetin reduced body weight gain and visceral and liver fat accumulation, and improved hyperglyceamia, hyperinsulinaemia, dyslipidaemia in mice fed a Western-style diet. Feeding a Western-style diet altered expression of genes related to inflammatory responses, lipid metabolism and oxidative phosphorylation in C57BL/6J mice after 20 weeks. The results from exhaustive gene expression analysis showed that quercetin minimally influenced hepatic gene expression in mice fed the Western diet. The gene screening results (GSEA) were consistent with the notion that it did improve mitochondrial function to some extent. Quantitative RT-PCR analysis indicated that quercetin did influence important regulators of fat accumulation and metabolic disorders. Our results suggest that quercetin reduces fat accumulation presumably through decreasing oxidative stress and increasing PPARα expression, and the following improvement of gene expression related to steatosis in the liver.
Project description:The effects of recombinant human GDF15 and matched caloric restriction in pair-fed controls on obesity and NAFLD in mice fed western diet high in both fat and fructose and housed at thermoneutrality (TN, 29 °C).
Project description:During the last few decades, the long-lasting consequences of nutritional programming during the early phase of life have become increasingly evident, but the effects of maternal nutrition on the developing intestine are currently still relatively underexplored. In this study, we investigated in mice the effects of a maternal Western-style (WS) high fat/cholesterol diet, given during the perinatal period, on gene expression and microbiota composition of two-week-old offspring. Microarray analysis revealed that a perinatal WS diet caused significant changes in gene expression in the small intestine and colon of the suckling offspring. A strong sexually dimorphic effect was observed in the affected genes. However, pathway analysis of the differentially expressed genes displayed that in both sexes metabolic and immune functions were strongly affected. Integration of the microbiota and gene expression data applying a multivariate correlation analyses revealed that Bacteroidaceae, Porphyromonadaceae and Lachnospiraceae were the bacterial families that most strongly correlated with gene expression in the colon and not with the bacterial families displaying the most pronounced change due to perinatal exposure to a WS diet. Amongst the genes demonstrating a strong correlation with one or more bacterial families were genes of key importance for intestinal development or functioning (i.e., Pitx2 and Ace2). In conclusion, our data demonstrate a strong programming effect of a maternal WS diet on the development of the intestine in the offspring. Small intestine and colon were isolated from two-week-old pups of dams fed a low- or Western-style high fat/cholesterol diet and subjected to gene expression profiling.
Project description:Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries. There is growing evidence that dysbiosis of the intestinal microbiota and disruption of microbiota-host interactions contribute to the pathology of NAFLD. We previously demonstrated that gut microbiota derived tryptophan metabolite indole-3-acetate (I3A) was decreased in both cecum and liver of high-fat diet-fed mice and attenuated the expression of inflammatory cytokines in macrophages and TNF-a and fatty acid induced inflammatory responses in an aryl-hydrocarbon receptor (AhR) dependent manner in hepatocytes. In this study, we investigated the effect of orally administered I3A in a mouse model of diet induced NAFLD. Western diet (WD)-fed mice given sugar water (SW) with I3A showed dramatically decreased serum ALT, hepatic TG, liver steatosis, hepatocyte ballooning, lobular inflammation, and hepatic production of inflammatory cytokines, compared to WD-fed mice given only SW. Metagenomic analysis show that I3A administration did not significantly modify the intestinal microbiome, suggesting that I3A’s beneficial effects likely reflect the metabolite’s direct actions on the liver. Administration of I3A partially reversed WD induced alterations of liver metabolome and proteome, notably, decreasing expression of several enzymes in hepatic lipogenesis and β- oxidation. Mechanistically, we also show that AMP-activated protein kinase (AMPK) mediates the anti-inflammatory effects of I3A in macrophages. The potency of I3A in alleviating liver steatosis and inflammation clearly demonstrates its potential as a therapeutic modality for preventing the progression of steatosis to NASH.
Project description:Bile acids are not only physiological detergents facilitating nutrient absorption, but also signaling molecules regulating metabolic homeostasis. We reported recently that transgenic expression of CYP7A1 in mice stimulated bile acid synthesis and prevented Western diet-induced obesity, insulin resistance and hepatic steatosis. The aim of this experiment is to determine the impact of induction of hepatic bile acid synthesis on liver metabolism by determining hepatic gene expression profile in CYP7A1 transgenic mice. CYP7A1 transgenic mice and wild type control mice were fed either standard chow diet or high fat high cholesterol Western diet for 4 month. Hepatic gene expressions were measured by microarray analysis. Our results indicate that hepatic bile acid synthesis is closely linked to cholesterogenesis and lipogenesis, and maintaining bile acid homeostasis is improtant in hepatic metabolic homeostasis. Male aged matched (~ 12-14 weeks) CYP7A1 transgenic mice and their wild type control littermates were fed a standard chow diet or a high fat (42%) high cholesterol (0.2%) diet (Harlan Teklad #88137) for 4 month Four groups (4 mice/group) are included in the experiments: Group 1: WT _ Chow Group 2: CYP7A1-tg + chow Group 3: WT + Western diet Group 4: CYP7A1-tg _ Western diet Total liver mRNA was isolated with a RNeasy kit (Qiagen) and used for microarray analysis.