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: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:Dietary flavonoids are supposed to be protective against cardiovascular diseases (CVD). Elevated circulating lipid levels and hepatic lipid accumulation are known risk factors for CVD. We investigated the effects and underlying molecular mechanisms of the flavonoid quercetin on hepatic lipid metabolism in mice with diet induced body weight gain and hepatic lipid accumulation. Adult male mice received a high-fat diet without or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Body weight gain was 29% lower in quercetin-fed mice (p<0.01), while the energy intake was not significantly different. Quercetin supplementation reduced hepatic lipid accumulation with 71% (p<0.05). 1H nuclear magnetic resonance serum lipid profiling revealed that the supplementation lowered serum lipids (p<0.0001). Global gene expression profiling of liver showed that key target genes of the transcription factor Constitutive androstane receptor (Car; official symbol Nr1i3) were regulated, in particular Cytochrome P450 2b (Cyp2b) genes. Quercetin can decrease high-fat diet induced body weight gain, hepatic lipid accumulation and serum lipid levels, which might be explained by the regulation of Cytochrome P450 genes under transcriptional control of CAR, an effect which is likely dependent on dietary background. Liver samples were obtained from 24 C57BL/6J male adult mice. All mice started with a three week adaptation phase, in which they were fed a normal-fat diet. During the intervention of 12 weeks, the mice received a high-fat diet without (HF) or with supplementation of 0.33% (w/w) quercetin (HF-Q). Based on visual inspection, three arrays lacked homogenous hybridization and were therefore excluded.
Project description:Dietary flavonoids are supposed to be protective against cardiovascular diseases (CVD). Elevated circulating lipid levels and hepatic lipid accumulation are known risk factors for CVD. We investigated the effects and underlying molecular mechanisms of the flavonoid quercetin on hepatic lipid metabolism in mice with diet induced body weight gain and hepatic lipid accumulation. Adult male mice received a high-fat diet without or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Body weight gain was 29% lower in quercetin-fed mice (p<0.01), while the energy intake was not significantly different. Quercetin supplementation reduced hepatic lipid accumulation with 71% (p<0.05). 1H nuclear magnetic resonance serum lipid profiling revealed that the supplementation lowered serum lipids (p<0.0001). Global gene expression profiling of liver showed that key target genes of the transcription factor Constitutive androstane receptor (Car; official symbol Nr1i3) were regulated, in particular Cytochrome P450 2b (Cyp2b) genes. Quercetin can decrease high-fat diet induced body weight gain, hepatic lipid accumulation and serum lipid levels, which might be explained by the regulation of Cytochrome P450 genes under transcriptional control of CAR, an effect which is likely dependent on dietary background.
Project description:We examined the effect of quercetin on the gene expression and function of epididymal adipose tissue (EAT) in Western diet-induced obese mice. Quercetin suppressed the increase in the number of macrophages and the decrease in the ratio of CD4+ to CD8+ T cells in EAT, and the elevation of plasma leptin and TNFα levels in mice fed the Western diet. Comprehensive gene expression analysis revealed that quercetin suppressed gene expression associated with the accumulation and activation of immune cells, including macrophages and lymphocytes in EAT. It also improved the expression of the oxidative stress-sensitive transcription factor NFκB, NADPH oxidases, and antioxidant enzymes. Quercetin markedly increased gene expression associated with mitochondrial oxidative phosphorylation and mitochondrial DNA Quercetin most likely universally suppresses the accumulation and activation of immune cells, including anti-inflammatory cells, whereas it specifically increased gene expression associated with mitochondrial oxidative phosphorylation. Suppression of oxidative stress and NFκB activity likely contributed to the prevention of the accumulation and activation of immune cells and resulting chronic inflammation. Quercetin most likely universally suppresses the accumulation and activation of immune cells, including anti-inflammatory cells, whereas it specifically increased gene expression associated with mitochondrial oxidative phosphorylation. Suppression of oxidative stress and NFκB activity likely contributed to the prevention of the accumulation and activation of immune cells and resulting chronic inflammation. C57BL/6J mice were fed a control diet; a Western diet high in fat, cholesterol, and sucrose; or the same Western diet containing 0.05% quercetin for 18 weeks.
Project description:transcription profiling by array of C57BL/6J mice fed a Western-style diet with or without 0.05% quercetin against mice on a control diet to study the effect of quercetin on obesity and hepatic gene expression
Project description:Consumption of a Western-style diet impairs the ovarian follicular microenvironment and preimplantation development without changes in insulin resistance and body fat percentage in non-human primates.
Project description:LV hypertrophy is associated with Western diet consumption, while intake of n-3 polyunsaturated fatty acids is associated with anti-hypertrophic effects. We treated rats for 12 weeks with either a Control diet, a Western diet or a Western + DHA diet. For each of the 3 dietary treatments there were 2 pooled samples of heart tissue (with each pooled sample representing 5 rats) for a total of 6 arrays. Microarray analysis identified 66 differentially expressed transcripts. Pathways were identified using Ingenuity and DAVID software. Array results from two pooled samples (5 rats in each pool) for n=10 per treatment group were used for comparisons. Comparisons between Western vs. Control, Western + DHA vs. Control and Western + DHA vs. Western diets was subjected to analysis to generate log fold changes. A dietary treatment of 12 weeks was used in an effort to produce LVH while limiting the development of comorbidities. Microarray analysis was performed on pooled samples, followed by qRT-PCR and Western blot analysis. Groups were Control, Western and Western + DHA. Comparisons between groups are expressed as LogFC (i.e. LogFC_WESvCTRL, LogFC_DHAVCTRL, LogFC_DHAvWES), available in Series supplementary files.
Project description:LV hypertrophy is associated with Western diet consumption, while intake of n-3 polyunsaturated fatty acids is associated with anti-hypertrophic effects. We treated rats for 12 weeks with either a Control diet, a Western diet or a Western + DHA diet. For each of the 3 dietary treatments there were 2 pooled samples of heart tissue (with each pooled sample representing 5 rats) for a total of 6 arrays. Microarray analysis identified 66 differentially expressed transcripts. Pathways were identified using Ingenuity and DAVID software. Array results from two pooled samples (5 rats in each pool) for n=10 per treatment group were used for comparisons. Comparisons between Western vs. Control, Western + DHA vs. Control and Western + DHA vs. Western diets was subjected to analysis to generate log fold changes.
Project description:We examined the effect of quercetin on the gene expression and function of epididymal adipose tissue (EAT) in Western diet-induced obese mice. Quercetin suppressed the increase in the number of macrophages and the decrease in the ratio of CD4+ to CD8+ T cells in EAT, and the elevation of plasma leptin and TNFα levels in mice fed the Western diet. Comprehensive gene expression analysis revealed that quercetin suppressed gene expression associated with the accumulation and activation of immune cells, including macrophages and lymphocytes in EAT. It also improved the expression of the oxidative stress-sensitive transcription factor NFκB, NADPH oxidases, and antioxidant enzymes. Quercetin markedly increased gene expression associated with mitochondrial oxidative phosphorylation and mitochondrial DNA Quercetin most likely universally suppresses the accumulation and activation of immune cells, including anti-inflammatory cells, whereas it specifically increased gene expression associated with mitochondrial oxidative phosphorylation. Suppression of oxidative stress and NFκB activity likely contributed to the prevention of the accumulation and activation of immune cells and resulting chronic inflammation. Quercetin most likely universally suppresses the accumulation and activation of immune cells, including anti-inflammatory cells, whereas it specifically increased gene expression associated with mitochondrial oxidative phosphorylation. Suppression of oxidative stress and NFκB activity likely contributed to the prevention of the accumulation and activation of immune cells and resulting chronic inflammation.