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GSE32357
Homo sapiens
20 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
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.
Publication Title
Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Exercise has a positive effect on overall health. This study was performed to get an overview of the effects of mixed exercise training on skeletal muscl
Publication Title
Identification of human exercise-induced myokines using secretome analysis.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Exercising is know to have an effect on exercising skeletal muscle, but unkown is the effect on non-exercising skeletal muscle. Gene expression changes in the non-exercising skeletal muscle would point to a signalling role of skeletal muscle
Publication Title
Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.
Sample Metadata Fields
Sex, Age, Specimen part, Race, Subject, Time
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue, a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPAR) in cold-induced browning. Here we aimed to investigate the importance of PPAR in driving transcriptional changes during cold-induced browning in mice. Male wildtype and PPAR/ mice were housed at thermoneutrality (28 C) or cold (5 C) for 10 days. Whole genome expression analysis was performed on inguinal WAT. In addition, other analyses were carried out. Whole genome expression data of livers of wildtype and PPAR/ mice fasted for 24 h served as positive control for PPAR-dependent gene regulation.Cold exposure increased food intake and decreased weight of BAT and WAT to a similar extent in wildtype and PPAR/ mice. Except for plasma non-esterified fatty acids, none of the cold-induced changes in plasma metabolites were dependent on PPAR genotype. Histological analysis of inguinal WAT showed clear browning upon cold exposure but did not reveal any morphological differences between wildtype and PPAR/ mice. Transcriptomics analysis of inguinal WAT showed a marked effect of cold on overall gene expression, as revealed by principle component analysis and hierarchical clustering. However, wildtype and PPAR/ mice clustered together, even after cold exposure, indicating a similar overall gene expression profile in the two genotypes. Pathway analysis revealed that cold upregulated pathways involved in energy usage, oxidative phosphorylation, and fatty acid -oxidation to a similar extent in wildtype and PPAR/ mice. Furthermore, cold-mediated induction of genes related to thermogenesis such as Ucp1, Elovl3, Cox7a1, Cox8, and Cidea, as well as many PPAR target genes, was similar in wildtype and PPAR/ mice. Finally, pharmacological PPAR activation had a minimal effect on expression of cold-induced genes in murine WAT.Cold-induced changes in gene expression in inguinal WAT are unaltered in mice lacking PPAR, indicating that PPAR is dispensable for cold-induced browning.
Publication Title
The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice.
Sample Metadata Fields
Sex
View Samples- Rattus norvegicus
- 3 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Aims/hypothesis: While lipid deposition in skeletal muscle is considered to be involved in obesity-associated insulin resistance, neutral intramyocellular lipid (IMCL) accumulation per se does not necessarily induce insulin resistance. We previously demonstrated that overexpression of the lipid droplet coat protein perilipin 2 augments intramyocellular lipid content while improving insulin sensitivity. Another member of the perilipin family, perilipin 5 (PLIN5), is predominantly expressed in oxidative tissues like skeletal muscle. Here we investigated the effects of PLIN5 overexpression in comparison with effects of PLIN2 on skeletal muscle lipid levels, gene expression profiles and insulin sensitivity. Methods: Gene electroporation was used to overexpress PLIN5 in tibialis anterior muscle of rats fed a high fat diet. Eight days after electroporation, insulin-mediated glucose uptake in skeletal muscle was measured by means of a hyperinsulinemic euglycemic clamp. Electron microscopy, fluorescence microscopy and lipid extractions were performed to investigate IMCL accumulation. Gene expression profiles were obtained using microarrays. Results: TAG storage and lipid droplet size increased upon PLIN5 overexpression. Despite the higher IMCL content, insulin sensitivity was not impaired and DAG and acylcarnitine levels were unaffected. In contrast to the effects of PLIN2 overexpression, microarray data analysis revealed a gene expression profile favoring FA oxidation and improved mitochondrial function. Conclusions/interpretation: Both PLIN2 and PLIN5 increase neutral IMCL content without impeding insulin-mediated glucose uptake. As opposed to the effects of PLIN2 overexpression, overexpression of PLIN5 in skeletal muscle promoted expression of a cluster of genes under control of PPAR and PGC1 involved in FA catabolism and mitochondrial oxidation.
Publication Title
Overexpression of PLIN5 in skeletal muscle promotes oxidative gene expression and intramyocellular lipid content without compromising insulin sensitivity.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Polyphenolic compounds, such as resveratrol, have recently received widespread interest due to their ability to mimic effects of calorie restriction. The objective of the present study was to gain more insight into the effects of 30 days resveratrol supplementation on adipose tissue morphology and underlying processes. Nine healthy obese men were supplemented with placebo and 150mg/day resveratrol for 30 days, separated by a 4-week washout period. A postprandial abdominal subcutaneous adipose tissue biopsy was collected to assess adipose tissue morphology and gene expression using microarray analysis. Resveratrol significantly decreased adipocyte size, with a shift towards a reduction in the proportion of large and very large adipocytes and an increase in small adipocytes. Microarray analysis revealed downregulation of Wnt, Notch and BMP/TGF- signaling pathways and upregulation of pathways involved in cell cycle after resveratrol supplementation, suggesting enhanced adipogenesis. Furthermore, the lysosomal/phagosomal pathway and the transcription factor EB were upregulated, reflecting an alternative pathway of lipid breakdown by autophagy. These data suggest that adipose tissue is an important target tissue for the effects of resveratrol in humans, but further research is necessary to investigate whether it translates into an improved adipose tissue function.
Publication Title
The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Treatment, Race, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Type 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid storage exceeds intracellular needs and induces lipotoxic events ultimately contributing to the development of insulin resistance. Lipid droplet (LD)-coating proteins may control proper lipid storage in skeletal muscle. Perilipin 2 (PLIN2/ADRP) is one of the most abundantly expressed LD-coating proteins in skeletal muscle. Here we examined the role of PLIN2 in myocellular lipid handling and insulin sensitivity by investigating the effects of in vitro PLIN2 knockdown and in vitro and in vivo overexpression. PLIN2 knockdown decreased LD formation and triacylglycerol storage, marginally increased FA oxidation, and increased incorporation of palmitate into diacylglycerols and phospholipids. PLIN2 overexpression in vitro increased intramyocellular TAG storage paralleled with improved insulin sensitivity. In vivo muscle-specific PLIN2 overexpression resulted in increased LD accumulation and blunted the high-fat diet-induced increase of OXPHOS protein content. Diacylglycerol levels were unchanged, while ceramide levels were increased. Despite the increased intramyocellular lipid accumulation, PLIN2 overexpression improved skeletal muscle insulin sensitivity. We conclude that PLIN2 is essential for lipid storage in skeletal muscle by enhancing the partitioning of excess FAs towards triacylglycerol storage in LDs thereby blunting lipotoxicity-associated insulin resistance.
Publication Title
Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The obese, insulin resistant state is characterized by impairments in lipid metabolism. Dietary polyphenols might improve these deteriorations. We have previously shown that 3-days supplementation of combined Epigallocatechin-gallate and Resveratrol (E+R) increased energy expenditure, which was accompanied by improved metabolic flexibility after a high-fat mixed-meal (HFMM) in men. The present study aimed to investigate whether these short-term effects translate into longer-term improvement of insulin sensitivity and lipid metabolism. In this randomized, double-blind study, 42 overweight subjects (21 male, 382 yrs, BMI 29.70.5 kg/m2, HOMA-IR 2.10.2) received either E+R (300 and 80 mg/d, respectively) or placebo (PLA) for 12 weeks (3 months). Before (t0) and after (t3) intervention, tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with stable isotope infusion. Fasting and postprandial (HFMM) lipid metabolism was assessed using indirect calorimetry and blood sampling. Adipose tissue and skeletal muscle lipolysis was measured using microdialysis in men and skeletal muscle biopsies were collected to assess mitochondrial function and gene expression alterations via microarray analysis. E+R supplementation increased fasting (P=0.06) and postprandial (P=0.03) fat oxidation but did not alter energy expenditure compared to PLA. This was accompanied by an E+R-induced increase in oxidative capacity in permeabilized muscle fibers (p<0.05). Moreover, E+R supplementation attenuated the increase in plasma triacylglycerol concentration that was observed in the PLA group (AUC, p<0.05), and tended to decrease visceral fat mass (P=0.09). Finally, insulin-stimulated glucose disposal and suppression of endogenous glucose production were not affected by E+R supplementation. 12 weeks E+R supplementation increased whole-body fat oxidation and skeletal muscle oxidative capacity, but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects.
Publication Title
Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of beige cells from murine white fat depots.
Publication Title
Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Peroxisome proliferator-activated receptor alpha (PPAR) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPAR target gene in liver, but its function in hepatic lipid metabolism is unknown. We investigated the regulation of vanin-1, and total vanin activity, by PPAR in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity. Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPAR activity. In addition, activation of mouse PPAR regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPAR, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPAR agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation. We show that hepatic vanin-1 is under extremely sensitive regulation by PPAR and that plasma vanin activity could serve as a readout of changes in PPAR activity in human subjects. In addition, our data propose a role for vanin-1 in regulation of hepatic TG levels during fasting.
Publication Title
PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples