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Expression patterns in liver after resveratrol treatment of mice on a high-calorie diet

ABSTRACT: Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including yeast, worms, and flies. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction (CR). Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan including increased insulin sensitivity, reduced IGF-1, increased AMPK and PGC-1α activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment (PAGE) revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal and point to new approaches for treating obesity-related disorders and diseases of ageing. Keywords: Drug treatment

ORGANISM(S): Mus musculus

PROVIDER: GSE6089 | GEO | 2006/11/03

SECONDARY ACCESSION(S): PRJNA97643

REPOSITORIES: GEO

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Transcription profiling of murine livers after resveratrol treatment of mice on a high-calorie diet

Project description:Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including yeast, worms, and flies. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction (CR). Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan including increased insulin sensitivity, reduced IGF-1, increased AMPK and PGC-1Î± activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment (PAGE) revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal and point to new approaches for treating obesity-related disorders and diseases of ageing. Experiment Overall Design: One-year-old male C57BL/6 mice were maintained on AIN-93G standard diet (SD), AIN-93G modified to provide 60% of calories from fat (HC), or HC diet with the addition of 0.04% resveratrol (HCR). Total RNA from the livers of 5 replicate animals from the first 2 groups and 4 from the 3rd group were labeled and hybridized to Agilent 44K whole genome microarrays.

2008-06-21 | E-GEOD-6089 | biostudies-arrayexpress

Calorie/Dietary Restriction and Resveratrol in Female Drosophila Melanogaster Head/Thorax

Project description:Feeding resveratrol to Drosophila melanogaster extends lifespan. Studies of microarray show similarities between calorie/dietary restriction and resveratrol on both a gene expression and biological pathway level. 9 samples: 3 biological replicates each of normal diet, restricted diet and normal diet plus resveratrol

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Calorie/Dietary Restriction and Resveratrol in Female Drosophila Melanogaster Head/Thorax

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Transcription profiling of mouse heart, brain, and skeletal muscle to determine the rffect of age, calorie restriction and resveratrol on gene expression

Project description:Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg-1 day-1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR. Experiment Overall Design: Heart, neocortex tissue, and gastrocnemius muscle was collected from young and old mice at 5 and 30 months of age, respectively; mice were subjected to either a calorie restricted diet or a control diet supplemented with resveratrol

2008-06-18 | E-GEOD-11291 | biostudies-arrayexpress

Effect of age, calorie restriction and resveratrol on gene expression in mouse heart, brain, and skeletal muscle

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Resveratrol Diet Aging (Heart, Liver, Muscle and Fat Tissue)

2008-08-05 | GSE11845 | GEO

Resveratrol Diet Aging (Heart, Liver, Muscle and Fat Tissue)

Project description:Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms. In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice shows a marked reduction in signs of aging including reduced albuminuria, decreased inflammation and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at mid-life. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started mid-life. Male C57BL/6NIA mice at 11 months of age were maintained on a standard purified mouse diet (AIN-93G) for one month prior to the start of the experiment. Beginning at one year of age, SD and EOD groups were fed a standard AIN-93G diet or AIN-93G plus 0.01% or 0.04% resveratrol for the duration of the study. Three separate groups were placed on an HC diet (AIN-93G modified by the addition of hydrogenated coconut oil to provide 60% of calories from fat) or HC + 0.01% or 0.04% resveratrol 6 weeks later and remained on those diets throughout the study. SD and HC mice were fed ad libitum. EOD mice were fed ad libitum on alternate days then moved to a separate cage without food for 24 h. Food intake and body weight were measured on a weekly basis for the duration of the study.

2008-08-04 | E-GEOD-11845 | biostudies-arrayexpress

Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans

Project description:Resveratrol is a naturally occurring compound that profoundly affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here we treated 10 healthy, obese men with placebo and 150 mg/day resveratrol in a randomized double-blind cross-over study for 30 days. Resveratrol supplementation significantly reduced sleeping- and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1alpha protein levels, increased citrate synthase activity, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels, and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces profound metabolic changes in obese subjects, mimicking the effects of calorie restriction.

2011-11-08 | GSE32357 | GEO

Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans

2011-11-08 | E-GEOD-32357 | biostudies-arrayexpress

Resveratrol prevents diet-induced arterial degeneration and stiffening in nonhuman primates

Project description:Cardiovascular (CV) disease is a leading cause of morbidity and mortality in Western societies. Even after accounting for traditional CV risk factors (e.g. obesity, smoking and hypertension), the inflammation-driven thickening and stiffening of central arteries is a strong predictor of adverse outcomes. Arterial wall changes are universally associated with advancing age and show unparalleled worsening in metabolic syndrome. In mice, resveratrol ameliorates a high-fat diet induced arterial wall inflammation and slows age-associated physiologic deteriorations within the arterial wall. Here we tested resveratrol in adult male rhesus monkeys, an experimental model relevant to humans. A diet rich in fat and sucrose (HFS) led to an increase in body weight as well as thickening and stiffening of the aortic wall, marked by diffuse inflammation, fibrosis and fat infiltration. Dietary resveratrol supplementation prevented diet-induced structural and functional alterations within the aortic wall, and abrogated the deleterious vascular endothelial and smooth muscle responses. Integrative genomic and proteomic analyses of aortic tissues revealed molecular signatures consistent with improved vascular functions. Thus, resveratrol conferred protection against the initiation of diet-induced inflammatory events that progress to pathological thickening and stiffening of large arteries. Dietary resveratrol may therefore hold promise as a novel therapy to ameliorate metabolic stress-induced CV disease. After baseline assessment, four male rhesus monkeys remained on the healthy standard diet (SD), 10 male rhesus monkeys were begun on a high fat/high sucrose (HFS) diet and 10 male rhesus monkeys were begun on a high fat/high sucrose (HFS) diet plus Resveratrol, 80mg/day. After one year of dietary intervention, the amount of resveratrol was increased to 240mg/day for one additional year. Tissues were then harvested for the array experiments.

2014-07-21 | E-GEOD-45927 | biostudies-arrayexpress

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