Project description:Evaluate differences in gene methylation levels between obese men with and without the metabolic syndrome Visceral adipose tissue from obese men with the metabolic syndrome (MetS+, N=7) vs. obese men without the metabolic syndrome (MetS-, N=7)
Project description:Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity.  Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure, and offers  insight into how obesity may propagate metabolic dysfunction to the next generation. Examination of the DNA methylation status, histone retention and sncRNA expression of the semen of 13 lean and 10 obese individuals; as well as the DNA methylation status of the semen of 6 obese men undergoing Roux-en-Y GBP surgery, at three time points: approximately 1 week before, 1 week after and 1 year after the surgery.
Project description:We have carried out whole-genome expression profiling of whole blood from obese subjects, defined as obese diet-sensitive and obese diet-resistant, and well matched lean individuals. The diet-sensitive or diet-resistant status refers to the different rates of weight loss observed in the two groups on a low-calorie diet regimen. Bioinformatic analysis revealed alterations in transcription in key pathways that are consistent with impaired capacity for fatty acid oxidation driven mitochondrial ATP synthesis in obese subjects who are resistant to weight loss. A total of 80 samples are analyzed. This consists of 20 lean subjects studied at one timepoint and 20 obese subjects (10 diet-sensitive and 10 diet-resistant) studied at 3 timepoints during caloric restriction (day of entry into program, week 3 into the program and week 6 into the program)
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:Individualized analysis through expression profiling of 20,000 probes in 28 tissue samples evaluated in subcutaneous and omental adipose tissue obtained during surgical intervention in non-obese and obese patients. Patients consisted of men and women of varying body size (lean to severely obese). Samples were collected at the time of operation in the fasting state. Samples consisted of subcutaneous and omental adipose tissue as well as a blood sample from lean and obese men and women removed in the fasting state at the time of surgery.
Project description:The goal of this work was to examine if reserveratrol or rosiglitazone treatment could improve the metabolic status of obese male ZDF rats after 6 weeks. Gene expression was analyzed in several key metabolic tissues, including liver, various white adipose tissue depots, red tibalus muscle, and whole blood.
Project description:The goal of this work was to examine if reserveratrol or rosiglitazone treatment could improve the metabolic status of obese male ZDF rats after 6 weeks. Gene expression was analyzed in several key metabolic tissues, including liver, various white adipose tissue depots, red tibalus muscle, and peripheral blood mononuclear cells.
Project description:The goal of this work was to examine if reserveratrol or rosiglitazone treatment could improve the metabolic status of obese male ZDF rats after 6 weeks. Gene expression was analyzed in several key metabolic tissues, including liver, various white adipose tissue depots, red tibalus muscle, and peripheral blood mononuclear cells.
Project description:We recruited ten normal-weight healthy men using inclusion criteria as previously described (Collet et al 2017). All males were healthy and not obese or overweight (average age: 23.8 years, average BMI (kg/m2): 23.3). Participants at baseline consumed a balanced diet (50% carbohydrate, 30% fat, and 20% protein). During caloric restriction, volunteers consumed 10% of normal energy requirement (226 kcal/d) for two days, again balanced (50% carbohydrate, 30% fat, and 20% protein), with the same macronutrient composition. After caloric restriction, volunteers were offered three substantial ad libitum buffet meals per day (20 MJ = 4,777 kcal) and additional snacks (16 MJ = 3,821 kcal) between meals for 2 days. They were invited to eat freely until comfortably full; food consumption was covertly measured. We collected fasting plasma samples at 0800 AM at baseline, after CR and refeeding (RF).