Project description:In order to explore the effect of hypertension and overweight/obesity on human visceral adipose tissue transcriptome, we collected three visceral adipose tissue samples from normal weight individuals (non hypertension), overweight/obese individuals (non hypertension) and overweight/obese individuals with hypertension, and sequenced their transcriptome.
Project description:The aim of this study was to analyze gene response to a 10-week dietary intervention for weight loss in peripheral blood mononuclear cells of overweight/obese male children. PBMCs were obtained from 12 overweight/obese boys for RNA extraction and hybridization on Affymetrix microarrays. We performed the microarray analysis at baseline and after a weight loss intervention program in a total of 24 samples. They were distributed by dietary response as high and low responders.
Project description:The purpose of this study was to evaluate the effect of progressive weight loss (5, 10, 15% weight loss) on metabolic function such as multi-organ insulin sensitivity and beta-cell function in obese people. We conducted microarray analysis to determine the effect of progressive weight loss on adipose tissue gene expression profile. We examined subcuntaneous adipose tissue samples obtained from 9 obese subjects before (A) and after 5% (B), 10% (C) and 15% (D) weight loss (total 36 samples).
Project description:The prevalence of obesity has been increasing rapidly worldwide during the past two decades. This is alarming, since obesity has considerable effects on morbidity and mortality. The majority of gene expression studies about the effect of obesity and weight loss have been performed using the adipose tissue for mRNA extraction. However, also the liver plays a central role in maintaining energy balance. To our knowledge, no overall analysis of hepatic gene expression in response to changes in nutritional status has been made in humans Therefore, it is important to investigate how a short-time hypocaloric diet affects overall hepatic gene expression and the metabolic profile in a group of overweight and obese women. The subjects (n=31) were middle-aged, overweight (BMI>25 kg/m2) women with gallstone disease scheduled for an elective gallbladder operation. The intervention subjects were placed on a hypocaloric AHA step I diet with a recommended daily energy intake of 5.0 MJ. The objective was to reduce 0.5 kg of body weight per week. The control subjects were instructed to continue their habitual diet and not to lose weight. Basic clinical measurements and laboratory analyses were performed twice at baseline and at two week intervals during the weight reduction period. Surgical liver biopsies were obtained at the end of the weight reduction period. RNA samples of 4 individuals from the intervention group and 4 individuals from the control group were selected for the microarray analysis. The results from the microarray analysis were fairly surprising. Only one gene was up-regulated and the rest 142 down-regulated in the diet intervention group compared to the control group when a minimum of 2-fold change was set as the limit. The global decrease in hepatic gene expression was unexpected but the results are interesting, with several genes not previously linked to weight reduction. The decrease in triglyceride and fasting plasma insulin concentrations observed in our study is in accordance with results from many previous weight-loss trials. Keywords: Overall hepatic gene expression associated with obesity and moderate weight loss in a group of overweight and obese middle-aged women.
Project description:The mechanisms responsible for weight loss-induced improvement in insulin sensitivity are partially understood. Greater insight can now be achieved through deep phenotyping and data integration. Here, we used an integrative approach to investigate associations between changes in insulin sensitivity and variations in lifestyle factors (diet and physical activity), subcutaneous adipose tissue (sAT) gene expression, metabolomics in serum, urine and feces, and gut microbiota composition after a 6-week calorie restriction period in overweight and obese adults
Project description:Activation of inflammatory pathways is one plausible mechanism underlying the association between obesity and increased breast cancer risk. However, macrophage infiltration and local biomarkers of inflammation in breast adipose tissue have seldom been studied in association with obesity. Gene expression profiles of normal breast tissue from reduction mammoplasty patients were evaluated by whole genome microarrays to identify patterns associated with obesity status (normal-weight, body mass index (BMI) <25; overweight, BMI 25-29.9; obese, BMI > or equal to 30). The presence of macrophage-enriched inflammatory loci with immunopositivity for CD68 protein was evaluated by immunohistochemistry (IHC). After adjusting for confounding by age, 760 genes were differentially expressed (203 up and 557 down; FDR = 0.026) between normal-weight and obese women. Gene ontology analysis suggested significant enrichment for pathways involving IL-6, IL-8, CCR5 signaling in macrophages and RXRalpha and PPARalpha activation, consistent with a pro-inflammatory state and suggestive of macrophage infiltration. Gene set enrichment analysis also demonstrated that the genomic signatures of monocytes and macrophages were over-represented in the obese group with FDR of 0.08 and 0.13, respectively. Increased macrophage infiltration was confirmed by IHC, which showed that the breast adipose tissue of obese women had higher average macrophage counts (mean = 8.96 vs. 3.56 in normal-weight women) and inflammatory foci counts (mean = 4.91 vs. 2.67 in normal-weight women). Obesity is associated with local inflammation and macrophage infiltration in normal human breast adipose tissues. Given the role of macrophages in carcinogenesis, these findings have important implications for breast cancer etiology and progression. 72 normal breast tissue samples from patients undergoing reduction mammoplasty. Reference design.
Project description:An ancillary study within a randomized trial of diet, exercise, or combined diet+exercise vs. control among overweight/obese postmenopausal women. Subcutaneous adipose-tissue biopsies were performed at baseline and after 6 months and changes in adipose-tissue gene expression were determined by microarray with an emphasis on pre-specified candidate pathways, as well as by unsupervised clustering. Analyses were conducted first by randomization group, and then by degree of weight change at 6-months in all women combined.
Project description:An ancillary study within a randomized trial of diet, exercise, or combined diet+exercise vs. control among overweight/obese postmenopausal women. Subcutaneous adipose-tissue biopsies were performed at baseline and after 6 months and changes in adipose-tissue gene expression were determined by microarray with an emphasis on pre-specified candidate pathways, as well as by unsupervised clustering. Analyses were conducted first by randomization group, and then by degree of weight change at 6-months in all women combined. Total RNA was obtained from subcutaneous adipose tissue biopsies at baseline and 6 months. A total of 47 women were biopsied and one replicate participant was included for a total of 96 samples.
Project description:Caloric restriction (CR) and methionine restriction driven enhanced lifespan and healthspan induces ‘browning’ of white adipose tissue (WAT), a metabolic response that increases heat production to defend core-body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight-loss induced by CR in humans reduces thiol-containing sulfur amino acid cysteine in WAT. Systemic cysteine-depletion in mice causes lethal weight-loss with increased fat utilization and browning of adipocytes that is rescued upon restoration of cysteine in diet. Mechanistically, cysteine restriction induced adipose browning and weight-loss requires sympathetic nervous system derived noradrenaline signaling via β3-adrenergic-receptors that is independent of FGF21 and UCP1. In obese mice, cysteine deprivation induced rapid adipose browning, increased energy expenditure leading to 30% weight-loss and reversed metabolic inflammation. These findings establish that cysteine is essential for organismal metabolism as removal of cysteine in the host triggers adipose browning and rapid weight loss.
Project description:Caloric restriction (CR) and methionine restriction driven enhanced lifespan and healthspan induces ‘browning’ of white adipose tissue (WAT), a metabolic response that increases heat production to defend core-body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight-loss induced by CR in humans reduces thiol-containing sulfur amino acid cysteine in WAT. Systemic cysteine-depletion in mice causes lethal weight-loss with increased fat utilization and browning of adipocytes that is rescued upon restoration of cysteine in diet. Mechanistically, cysteine restriction induced adipose browning and weight-loss requires sympathetic nervous system derived noradrenaline signaling via β3-adrenergic-receptors that is independent of FGF21 and UCP1. In obese mice, cysteine deprivation induced rapid adipose browning, increased energy expenditure leading to 30% weight-loss and reversed metabolic inflammation. These findings establish that cysteine is essential for organismal metabolism as removal of cysteine in the host triggers adipose browning and rapid weight loss.