Project description:Genome-wide DNA methylation profiling of healthy young men following a control and high-fat overfeeding diet using Illumina's Infinium 27k Human DNA methylation Beadchip v. 1.2. DNA methylation profiles were obtained for 27,578 CpG sites in human skeletal muscle. Randomized cross-over desgin, where all subjects receieved both treatments (control and high-fat overfeeding diet). Biopsies were obtained from 23 different individuals amounting to 22 samples following the control diet and 22 samples following the high-fat overfeeding diet (paired n=21). Bisulphite converted DNA from the 44 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.
Project description:Genome-wide DNA methylation profiling of healthy young men following a control and high-fat overfeeding diet using Illumina's Infinium 27k Human DNA methylation Beadchip v. 1.2. DNA methylation profiles were obtained for 27,578 CpG sites in human skeletal muscle.
Project description:Genome-wide DNA methylation profiling of young men born with low birth weight following a control and high-fat overfeeding diet using Illumina's Infinium 27k Human DNA methylation Beadchip v. 1.2. DNA methylation profiles were obtained for 27,578 CpG sites in human skeletal muscle. Randomized cross-over desgin, where all subjects receieved both treatments (control and high-fat overfeeding diet). Biopsies were obtained from 17 different individuals amounting to 16 samples following the control diet and 15 samples following the high-fat overfeeding diet (paired n=14). Bisulphite converted DNA from the 31 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.
Project description:Genome-wide DNA methylation profiling of young men born with low birth weight following a control and high-fat overfeeding diet using Illumina's Infinium 27k Human DNA methylation Beadchip v. 1.2. DNA methylation profiles were obtained for 27,578 CpG sites in human skeletal muscle.
Project description:The adaptive mechanisms in response to excess energy supply are still poorly known in humans. Our aims were to define metabolic responses and changes in gene expression in adipose tissue of healthy volunteers during fat overfeeding. Healthy lean and overweight subjects were submitted to a high fat diet during 56 days. Adipose tissue biopsies were taken at Day 0, Day 14 and Day 56.
Project description:Epidemiological data suggest that lean individuals resist exposure to the obesogenic environment better than those with obesity. To test this, we analyzed the relationship between overfeeding-induced weight and fat mass gains with baseline body mass index (BMI) and body fat percentage. In this controlled intervention study, 34 young men (BMI: 25.5±2.4 kg/m2, body fat [DXA]: 19.3±5.1%) consumed for 8 weeks 40% more energy than needed at weight maintenance. The energy costs of weight and fat mass gain were calculated as the 8-week excess energy consumed (EEC) divided by weight or fat mass gain. Energy expenditure (baseline and after overfeeding) was determined using a metabolic chamber and doubly labeled water. Transcriptomic analysis was conducted from abdominal subcutaneous adipose tissue samples
Project description:Dietary protein restriction has been shown to increase energy expenditure and to improve insulin sensitivity in mice, but it is unknown whether humans exhibit similar phenotype to a prolonged eucaloric protein-restricted diet that meet daily protein minimum requirements. We hypothesize that a protein-restricted diet would necessitate an increase in energy intake in order to maintain body weight in healthy, lean men. We designed an overall amino acid diluted diet meeting the requirement for daily protein intake and essential amino acids. Healthy, young, lean men adhered to a protein-restricted, high-carbohydrate diet (LPHC: protein 9E%, 70E% carbohydrate, and 21E% fat) or a protein-restricted, high-fat diet (LPHF: 9E% protein, 50E% fat, and 40E% carbohydrate) for 5 weeks, followed by another 5 weeks on a higher, standard protein diet (HPD: 18E% protein), reflecting their habitual diet. The diets were eucaloric, and energy provision was adjusted to maintain body weight throughout the interventions. In addition, wild type (WT), and FGF21 knockout mice were also fed LPHC, LPHF diets, or a standard higher diet (HPD) for a total of 10 weeks. Our results showed that prolonged eucaloric LPHC and LPHF diets necessitated a daily increase of 20-21% (2.5 MJ) in food intake to maintain body weight compared to pre-intervention in healthy, lean men. Additionally, fasting plasma FGF21 levels increased from 90±125 pg/ml and 78±34 pg/ml to 257±99 pg/ml and 160±52 pg/ml at the end of the LPHC and LPHF, respectively. Furthermore, proteomic analysis revealed adaptations in the respiratory chain in human adipose tissue after 5-week protein-restricted diets. This was found to be dependent on FGF21 in mice, indicating increased energy utilization through alternative UCP1-independent futile cycle pathways likely mediated by FGF21. Moreover, whole-body insulin sensitivity, measured by a hyperinsulinemic-euglycemic clamp, was increased by 16% after the LPHC intervention while maintained after the LPHF intervention, despite the high fat intake. These findings suggest that a protein-restricted diet could serve as a promising approach to prevent weight gain and comorbidities associated with obesity.
Project description:Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different non-human organisms. Only a limited number of CR studies have been performed in humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a 30% CR diet in immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-34, and nine healthy old men, aged 64-85, were subjected to a two week weight maintenance diet, followed by three weeks of 30% CR. Before and after 30% CR, peripheral blood mononuclear cellsâ (PBMCs) whole genome gene expression was assessed. Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in immune response in young men, but not in old men. At baseline, immune response-related genes were already higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling immune response, and were inhibited in young men upon CR, and activated in old men at baseline. Based on the gene expression data, we conclude that a short period of CR is more effective in young men compared to old men regarding immune related pathways. Gene expression was profiled in peripheral blood mononuclear cells (PBMCs) from young and old men before and after 30% caloric restriction.
Project description:Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different non-human organisms. Only a limited number of CR studies have been performed in humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a 30% CR diet in immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-34, and nine healthy old men, aged 64-85, were subjected to a two week weight maintenance diet, followed by three weeks of 30% CR. Before and after 30% CR, peripheral blood mononuclear cells’ (PBMCs) whole genome gene expression was assessed. Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in immune response in young men, but not in old men. At baseline, immune response-related genes were already higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling immune response, and were inhibited in young men upon CR, and activated in old men at baseline. Based on the gene expression data, we conclude that a short period of CR is more effective in young men compared to old men regarding immune related pathways.