Quercetin decreases high-fat diet induced bodyweight gain and accumulation of hepatic and circulating lipids in mice.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE51343 | GEO | 2014/10/14
SECONDARY ACCESSION(S): PRJNA222808
REPOSITORIES: GEO
Similar Datasets
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.
2014-10-14 | E-GEOD-51343 | biostudies-arrayexpress
Project description:Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on hepatic lipid metabolism and detailed serum lipid profiles, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to measure quantitatively serum lipid profiles and whole genome microarray analysis was used to identify the responsible mechanisms in liver. There were no significant differences found in mean body weight, energy intake and hepatic lipid accumulation between the quercetin and control group. In serum of quercetin-fed mice, TG levels were decreased with 15%, poly unsaturated fatty acids (PUFA) were increased with 14% and saturated fatty acids were decreased. Palmitic acid, oleic acid, and linoleic acid were all decreased in quercetin-fed mice by 9-15%. Both palmitic acid and oleic acid can be oxidized by omega-oxidation. Indeed, gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially omega-oxidation. At the gene level, this was reflected by the up regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, Cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor Constitutive androstane receptor (Car; official symbol Nr1i3) were also up regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid omega-oxidation and lowered corresponding circulating lipid levels, a process that may involve Por and Car, and results in a potential beneficial CVD preventive effect. Liver samples were obtained from 36 C57BL/6J male adult mice. All mice started with a three week adaptation phase, in which they were fed a mild-high-fat diet. 12 mice were sacrificed immediately after the adaptation phase (t=0). The other 24 mice received the mild-high-fat diet without (HF) or with supplementation of 0.33% (w/w) quercetin (HF-Q) for 12 weeks.
2013-02-05 | E-GEOD-39140 | biostudies-arrayexpress
Project description:Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on hepatic lipid metabolism and detailed serum lipid profiles, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to measure quantitatively serum lipid profiles and whole genome microarray analysis was used to identify the responsible mechanisms in liver. There were no significant differences found in mean body weight, energy intake and hepatic lipid accumulation between the quercetin and control group. In serum of quercetin-fed mice, TG levels were decreased with 15%, poly unsaturated fatty acids (PUFA) were increased with 14% and saturated fatty acids were decreased. Palmitic acid, oleic acid, and linoleic acid were all decreased in quercetin-fed mice by 9-15%. Both palmitic acid and oleic acid can be oxidized by omega-oxidation. Indeed, gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially omega-oxidation. At the gene level, this was reflected by the up regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, Cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor Constitutive androstane receptor (Car; official symbol Nr1i3) were also up regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid omega-oxidation and lowered corresponding circulating lipid levels, a process that may involve Por and Car, and results in a potential beneficial CVD preventive effect.
2013-02-05 | GSE39140 | GEO
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.
2012-05-29 | E-GEOD-38141 | biostudies-arrayexpress
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.
2012-05-30 | GSE38141 | GEO
Project description:We have previously shown that paramylon (PM) supplementation to a high fat diet reduces the postprandial glucose rise, serum total and LDL-cholesterol, and abdominal fat accumulation in mice; however, the mechanism has not been determined. We evaluated the potential mechanism in male C57BL/6J mice fed a high-fat diet supplemented with 5% PM powder, extracted from Eu-glena gracilis, for 12 weeks. Abdominal fat weight, and serum lipids were measured; ileal and hepatic mRNA expression were assessed using DNA microarray and real-time PCR. The poten-tial mechanism of PM on modulating lipid metabolism was explored by gene ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Dietary supplementation with PM resulted in decreased abdominal fat accumulation and serum LDL-cholesterol concentrations via suppression of the digestion and absorption pathway in the ileum and activation of the hepatic PPAR signaling pathway. Improvement in glucose tolerance may be the result of lipid metabolism modification because the glucose metabolism pathway was not detected by GO classification and KEGG pathway analysis. PM intake also directly enhanced immunoglobulin production.
2021-08-04 | GSE181289 | GEO
Project description:Both the 0.05% and 1% querceitn diets did not significantly affect the body weight, fat accumulation, and blood components. However, 0.05% quercetin significantly increased the glutathione/oxidized glutathione ratio in the liver. Moreover, the 1% quercetin diet reduced the lipid peroxidation markers 8-isoprostane in plasma and malondialdehyde in the liver, epididymal adipose tissues, and small intestine. Although comprehensive gene expression analysis dot not detect the genes with significantly different expression levels among the groups of mice, RT-PCR analysis showed that the 1% quercetin diet significantly induced the expression of the antioxidant enzymes Gpx1, Cat, and Sod1 in the liver and Gpx1 and Cat in the epididymal adipose tissues. The transcription factor nuclear factor E2-related factor 2 (Nrf2) was slightly induced in the nuclear fraction of the livers of mice fed the 1% quercetin diet. Quercetin may induce antioxidant enzymes by directly or indirectly activating the Nrf2 pathway in the liver. Five-week-old male mice were fed a AIN-93G diet containing 0% (Control), 0.05% (0.05% quercetin diet), or 1% quercertin (1% quercetin diet) for 20 weeks.
2015-07-24 | E-GEOD-62805 | biostudies-arrayexpress
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Experiment Overall Design: All animals were adapted to the RM3 (E) 801710 Soya-free powdered diet (B. S & S. [Scotland] Ltd, UK) over a period of 14 days. Quercetin was added separately to the semi-purified diets at a concentration of 6200 ppm (0.62 %; 6.2 g per kg). 65 male cytochrome P450 reductase null (KO) mice and 65 wild type (WT) C57BL/6 mice were reared, all aged between 6-8 weeks. Animals were housed 3 per cage, where both temperature and relative humidity were maintained within a range of 19-23oC and 40-70%, respectively. Twelve-hour periods of light were cycled with twelve-hour periods of darkness. Experiment Overall Design: For each strain of mouse, the following experimental design was used: a control group (25 mice) receiving powdered RM3 diet ad libitum and a group (25 mice) receiving a âhigh doseâ of quercetin (7 mg / mouse). The experimental diet was administered on day 15, following a 14-day adaptation period to the RM3 diet. Animals were sacrificed after 24 h. Experiment Overall Design: RNA samples destined for microarray analysis were only accepted and pooled into three groups if no aberrant signs of degradation (e.g. multiple peaks) were observed. The comprehensive gene expression profiles of the liver, jejunum, ileum, and colon were analyzed. In all cases, except those listed, RNA from 3 mice was pooled to form sample 1, another 3 mice to form sample 2, etc. Thus, 9 mice were used for the four experimental groups: wild-type, wild-type+quercetin, POR-null, POR-null+quercetin.
2008-06-13 | E-GEOD-4256 | biostudies-arrayexpress
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Experiment Overall Design: All animals were adapted to the RM3 (E) 801710 Soya-free powdered diet (B. S & S. [Scotland] Ltd, UK) over a period of 14 days. Quercetin was added separately to the semi-purified diets at a concentration of 6200 ppm (0.62 %; 6.2 g per kg). 65 male cytochrome P450 reductase null (KO) mice and 65 wild type (WT) C57BL/6 mice were reared, all aged between 6-8 weeks. Animals were housed 3 per cage, where both temperature and relative humidity were maintained within a range of 19-23oC and 40-70%, respectively. Twelve-hour periods of light were cycled with twelve-hour periods of darkness. Experiment Overall Design: For each strain of mouse, the following experimental design was used: a control group (25 mice) receiving powdered RM3 diet ad libitum and a group (25 mice) receiving a â??high doseâ?? of quercetin (7 mg / mouse). The experimental diet was administered on day 15, following a 14-day adaptation period to the RM3 diet. Animals were sacrificed after 24 h. Experiment Overall Design: RNA samples destined for microarray analysis were only accepted and pooled into three groups if no aberrant signs of degradation (e.g. multiple peaks) were observed. The comprehensive gene expression profiles of the liver, jejunum, ileum, and colon were analyzed. In all cases, except those listed, RNA from 3 mice was pooled to form sample 1, another 3 mice to form sample 2, etc. Thus, 9 mice were used for the four experimental groups: wild-type, wild-type+quercetin, POR-null, POR-null+quercetin.
2008-06-13 | E-GEOD-4259 | biostudies-arrayexpress
Project description:Using mice deficient in hepatic cytochrome-P450 oxidoreductase (POR), which disables the liver cytochrome P450 system, the metabolism and biological response of the anti-carcinogenic flavonoid, quercetin, was examined. Profiling circulating metabolites revealed similar profiles over 72 h in wild type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that 2-3 fold more genes responded significantly to quercetin in WT compared to KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism were predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase I detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction. Experiment Overall Design: All animals were adapted to the RM3 (E) 801710 Soya-free powdered diet (B. S & S. [Scotland] Ltd, UK) over a period of 14 days. Quercetin was added separately to the semi-purified diets at a concentration of 6200 ppm (0.62 %; 6.2 g per kg). 65 male cytochrome P450 reductase null (KO) mice and 65 wild type (WT) C57BL/6 mice were reared, all aged between 6-8 weeks. Animals were housed 3 per cage, where both temperature and relative humidity were maintained within a range of 19-23oC and 40-70%, respectively. Twelve-hour periods of light were cycled with twelve-hour periods of darkness. Experiment Overall Design: For each strain of mouse, the following experimental design was used: a control group (25 mice) receiving powdered RM3 diet ad libitum and a group (25 mice) receiving a âhigh doseâ of quercetin (7 mg / mouse). The experimental diet was administered on day 15, following a 14-day adaptation period to the RM3 diet. Animals were sacrificed after 24 h. Experiment Overall Design: RNA samples destined for microarray analysis were only accepted and pooled into three groups if no aberrant signs of degradation (e.g. multiple peaks) were observed. The comprehensive gene expression profiles of the liver, jejunum, ileum, and colon were analyzed. In all cases, except those listed, RNA from 3 mice was pooled to form sample 1, another 3 mice to form sample 2, etc. Thus, 9 mice were used for the four experimental groups: wild-type, wild-type+quercetin, POR-null, POR-null+quercetin.
2008-06-13 | E-GEOD-4257 | biostudies-arrayexpress