Increased trunk fat is associated with altered gene expression in breast tissue of normal weight women
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PROVIDER: EGAS00001005138 | EGA |
REPOSITORIES: EGA
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Project description:Lymphocyte and breast tissue samples from overweight woman at increased risk of breast cancer before and after 1 month of intermittant energy restriction Introduction Observational studies indicate that weight loss and energy restriction reduce breast cancer risk. Intermittent energy restriction (IER) reduces weight as well as, or more than continuous energy restriction (CER), but its effect on the breast and systemic metabolism as indicators of breast cancer risk are not known. Methods We assessed the effect of IER ( 2 days of 65% energy restriction) for one menstrual cycle on the breast (breast gene expression and fat cell size) and systemic metabolism (insulin resistance, lipids, serum and urine metabolites) in 23 overweight premenopausal women at high risk of breast cancer. Unsupervised hierarchical analysis selected 100 genes with the highest variance between pre and post IER biopsies in 20 subjects, whilst mass spectrometry was used to assess corresponding changes in serum (LCMS) and urine metabolites (GCMS) in 23 subjects in the restricted and unrestricted days of the IER. Results Women lost on average 4.8% (± 2.0) of body weight and 8.0% (± 5.0) of body fat. Insulin resistance (HOMA) was reduced by 29.8% (±17.8) on the restricted days and by 11%(±34) on the unrestricted days of the IER. Over 250 serum and urine metabolites significantly increased or decreased during the two restricted days and most returned to normal after the subsequent five day period . In the breast tissue, approximately half (In 11) of the subjects displayed down regulation of several metabolic pathways including lipid synthesis, growth factors and hormones, whilst epithelial genes including milk proteins, secretoglobulins and mucins were up-regulated and several metabolic pathways down-regulated including lipid synthesis, growth factors and hormones. In the other nine subjects there was no appreciable effect of IER on the breast. CorrespondingThe gene changes were not seen in peripheral blood lymphocytes, and there was no reduction in breast fat cell size. The two groups defined by change in gene expression or lack of it did not differ in the degree of weight or fat loss, other systemic metabolic markers, or histological assessment of the biopsies. Conclusion We conclude that breasts vary in response to short-term IER, the mechanism of which requires further investigation. Trial registration ISRCTN77916487
2016-07-13 | GSE66161 | GEO
Project description:The popularity of high fat foods in modern society has been associated with epidemic of various metabolic diseases characterized by insulin resistance, the pathology of which involves complex interactions between multiple tissues such as liver, skeletal muscle and white adipose tissue (WAT). To uncover the mechanism by which excessive fat impairs insulin sensitivity, we conducted a multi- tissue study by using TMT-based quantitative proteomics. 3-week-old ICR mice were fed with high fat diet (HFD) for 19 weeks to induce insulin resistance. Liver, skeletal muscle and epididymal fat were collected for proteomics screening. Additionally, PRM was used for validating adipose differential proteins. By comparing tissue-specific protein profiles of HFD mice, multi-tissue regulation of glucose and lipid homeostasis and corresponding underlying mechanisms was systematically investigated and characterized. NC: normal birth weight + chow diet; NH: normal birth weight + high fat diet; LC: low birth weight + chow diet; LH: low birth weight + high fat diet.
2022-01-26 | PXD021046 | Pride
Project description:Using a C57BL6/J mouse model of diet-induced obesit,we observed that mannose supplementation of high fat diet (HFD)-fed mice prevents weight gain,lowers adiposity, reduces liver steatosis, and improves glucose tolerance and insulin sensitivity. We used microarrays to determine the gene expression pattern in epididymal fat frommice weaned on Normal diet (ND), HFD and HFD with mannose (HFDM)
2018-11-06 | GSE110333 | GEO
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
2025-04-28 | GSE294614 | GEO
Project description:Smokers weigh less and have less body fat than non-smokers, and increased body fat and weight gain are observed following smoking cessation. To assess a possible molecular mechanism underlying the inverse association between smoking and body weight, we hypothesized that smoking may induce the expression of a fat depleting gene in the airway epithelium, the cell population that takes the brunt of the stress of cigarette smoke. As a candidate gene we evaluated the expression of alpha2-zinc-glycoprotein1 (AZGP1), a soluble protein that stimulates lipolysis, induces a reduction in body fat in mice and is associated with the cachexia related to cancer, and is known to be expressed in secretory cells of lung epithelium. To assess if smoking upregulates AZGP1 expression, microarray analysis with TaqMan confirmation was used to evaluate large airway epithelial samples obtained by fiberoptic bronchoscopy from 37 normal smokers and 55 normal nonsmokers. Both microarray and TaqMan analysis demonstrated that AZGP1 mRNA levels were higher in the large airway epithelium of normal smokers compared to normal nonsmokers (p<0.05, all comparisons). Western analysis of airway biopsies of smokers compared with nonsmokers demonstrated upregulation of AZGP1 at the protein level, and immunohistochemical analysis demonstrated upregulation of AZGP1 in secretory as well as neuroendocrine cells of smokers. In the context that AZGP1 is involved in lipolysis and fat loss, its overexpression in the airway epithelium of chronic smokers may represent one mechanism for the weight difference in smokers vs nonsmokers. Keywords: Comparison of gene expression in large airway epithleium of normal non-smokers and normal smokers
2009-01-06 | GSE10135 | GEO
Project description:Smokers weigh less and have less body fat than non-smokers, and increased body fat and weight gain are observed following smoking cessation. To assess a possible molecular mechanism underlying the inverse association between smoking and body weight, we hypothesized that smoking may induce the expression of a fat depleting gene in the airway epithelium, the cell population that takes the brunt of the stress of cigarette smoke. As a candidate gene we evaluated the expression of alpha2-zinc-glycoprotein1 (AZGP1), a soluble protein that stimulates lipolysis, induces a reduction in body fat in mice and is associated with the cachexia related to cancer, and is known to be expressed in secretory cells of lung epithelium. To assess if smoking upregulates AZGP1 expression, microarray analysis with TaqMan confirmation was used to evaluate large airway epithelial samples obtained by fiberoptic bronchoscopy from 37 normal smokers and 55 normal nonsmokers. Both microarray and TaqMan analysis demonstrated that AZGP1 mRNA levels were higher in the large airway epithelium of normal smokers compared to normal nonsmokers (p<0.05, all comparisons). Western analysis of airway biopsies of smokers compared with nonsmokers demonstrated upregulation of AZGP1 at the protein level, and immunohistochemical analysis demonstrated upregulation of AZGP1 in secretory as well as neuroendocrine cells of smokers. In the context that AZGP1 is involved in lipolysis and fat loss, its overexpression in the airway epithelium of chronic smokers may represent one mechanism for the weight difference in smokers vs nonsmokers. Keywords: Comparison of gene expression in large airway epithleium of normal non-smokers and normal smokers Airway epithelial cells obtained by bronchoscopy with brushing from healthy smokers and healthy non-smokers
2009-01-06 | E-GEOD-10135 | biostudies-arrayexpress
Project description:Experiment on MolOBB dataset by Novo Nordisk. Expression profiling of gluteal and abdominal fat biopsies and whole blood from obese and normal weight patients.
2010-09-10 | E-MTAB-54 | biostudies-arrayexpress
Project description:Fat and lean broilers have similar body weight but acquire a divergent abdominal fat content
2021-03-13 | PXD024710 |
Project description:Background Obesity is associated with changes in fat cell gene expression and metabolism. What drives these changes is not well understood. We aimed to explore fat cell epigenetics, i.e., DNA methylation, as one mediator of gene regulation, in obese women. The global DNA methylome for abdominal subcutaneous fat cells was compared between 15 obese case (BMI 41.4 ± 4.4 kg/m 2 , mean ± SD) and 14 never-obese control women (BMI 25.2 ± 2.5 kg/m 2 ). Global array-based transcriptome analysis was analyzed for subcutaneous white adipose tissue (WAT) from 11 obese and 9 never-obese women. Limma was used for statistical analysis. Results We identified 5529 differentially methylated DNA sites (DMS) for 2223 differentially expressed genes between obese cases and never-obese controls (false discovery rate <5 %). The 5529 DMS displayed a median difference in beta value of 0.09 (range 0.01 to 0.40) between groups. DMS were under-represented in CpG islands and in promoter regions, and over-represented in open sea-regions and gene bodies. The 2223 differentially expressed genes with DMS were over-represented in key fat cell pathways: 31 of 130 (25 %) genes linked to “adipogenesis” (adjusted P = 1.66 × 10 −11 ), 31 of 163 (19 %) genes linked to “insulin signaling” (adjusted P = 1.91 × 10 −9 ), and 18 of 67 (27 %) of genes linked to “lipolysis” (P = 6.1 × 10 −5 ). In most cases, gene expression and DMS displayed reciprocal changes in obese women. Furthermore, among 99 candidate genes in genetic loci associated with body fat distribution in genome-wide association studies (GWAS); 22 genes displayed differential expression accompanied by DMS in obese versus never-obese women (P = 0.0002), supporting the notion that a significant proportion of gene loci linked to fat distribution are epigenetically regulated. Conclusions Subcutaneous WAT from obese women is characterized by congruent changes in DNA methylation and expression of genes linked to generation, distribution, and metabolic function of fat cells. These alterations may contribute to obesity-associated metabolic disturbances such as insulin resistance in women. The global DNA methylome in abdominal subcutaneous fat cells was compared between 15 obese cases (BMI 41.4±4.4 kg/m2, mean ± SD) and 14 never-obese control women (BMI 25.2±2.5 kg/m2).
2015-09-15 | E-GEOD-67024 | biostudies-arrayexpress
Project description:Increased trunk fat is associated with an elevated risk of breast cancer in normal-weight postmenopausal women. The main objective of this study was to determine whether levels of trunk fat are associated with changes in breast gene expression in normal-weight women. Non-tumorous breast tissue was collected from 32 normal BMI women who underwent mastectomy for breast cancer risk reduction or treatment. Body composition was measured by dual-energy x-ray absorptiometry. High levels of trunk fat were associated with a large number of differentially expressed genes and changes in multiple pathways and processes potentially linked to breast cancer pathogenesis. High levels of trunk fat were also associated with an elevated immune score and increased levels of leptin, CCL2, VEGF-C, IL6, and aromatase. Collectively, these results help to explain why high levels of trunk fat are associated with an increased risk of breast cancer in normal BMI women.
| S-EPMC8795267 | biostudies-literature