Gene Expression in Adipose Tissue during Weight Loss
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE11975 | GEO | 2009/05/12
SECONDARY ACCESSION(S): PRJNA105851
REPOSITORIES: GEO
Similar Datasets
Project description:We investigated the regulation of adipose tissue (AT) gene expression during different phases of a dietary weight loss program and its relationship with insulin sensitivity. Obese women followed a weight reduction program composed of an energy restriction phase (ER) with a 4-week very-low-calorie diet and a weight stabilization period (WS) composed of a 2-month low-calorie diet followed by 3 to 4 months of a weight maintenance diet. At each time point, body composition, plasma parameters and glucose disposal rate were assessed and subcutaneous AT biopsies were performed. Variations in mRNA levels were determined using DNA microarrays and reverse transcription-quantitative PCR. Distinct sets of AT genes are regulated during calorie restriction and weight stabilization revealing an unexpected temporal pattern in the link between AT and insulin sensitivity during weight loss. Experiment Overall Design: Fifteen obese premenopausal women were recruited at the Third Faculty of Medicine of Charles University and at the Institute for Mother and Child Care in Prague, Czech Republic. During the first four weeks of the dietary intervention program, the subjects received an energy restricted diet of 800 kcal/day (liquid formula diet, Redita, Promil). During the next two months, a low-calorie diet was designed to provide 600 kcal/day less than the individually estimated energy requirement based on an initial resting metabolic rate multiplied by 1.3. Following this, subjects entered a weight maintenance phase for a period of 3 to 4 months, during which the patients were instructed to keep their weight stable. A complete clinical investigation in the fasting state was realized before and at the end of each phase. Needle microbiopsy of subcutaneous AT was performed under local anesthesia (1% Xylocaine) from the abdominal region (14â20 cm lateral to the umbilicus). Total RNA were isolated from AT samples with Qiagen RNeasy kit. RNA quantity and quality were checked with the Experion automated electrophoresis system (BioRad laboratories). We performed a whole transcriptome analysis comparing 1) before vs. after the initial 4 weeks severe energy restriction (ER), 2) after energy restriction vs. after weight stabilization (WS) and 3) before dietary intervention vs. after weight stabilization (DI). Eight subjects representative of the cohort were selected, matched for high quality of total RNA samples, insulin sensitivity and weight changes during the study. Targets for microarray experiments were generated from 500 ng of total RNA with Agilent low RNA input amplification kit (Agilent Technologies) and hybridized to whole genome 44k oligonucleotide arrays (Agilent Technologies). Each combination of samples was analyzed twice using a dye swap design (i.e., a total of 48 hybridizations). Data acquisition from microarrays was obtained with a GenePix 4000B scanner (Axon instruments) and image processing was performed with Feature Extraction 8.5 (Agilent Technologies). Raw data were normalized with a global Lowess procedure and filtered with R package LIMMA (Bioconductor). Outlier replicates and spots with a signal to noise ratio lesser than 2 on both red and green channel were eliminated from our analyses. Mean log ratios were calculated from paired duplicates before normalization. Differentially expressed genes were identified with Significance Analysis of Microarray (SAM) procedure.
2009-05-16 | E-GEOD-11975 | biostudies-arrayexpress
Project description:The additional therapeutic effects of regular exercise during a dietary weight loss program in people with obesity and prediabetes are unclear. We evaluated the effect of 10% weight loss, induced within ~5 months by calorie-restriction alone (Diet-ONLY, n=8) or calorie-restriction plus multi-modal exercise training (Diet+EX, n=8), on metabolic function in people with obesity and prediabetes. Whole-body (primarily muscle) and hepatic insulin sensitivity were 2-3 fold greater in the Diet+EX than the Diet-ONLY group, and were accompanied by increased muscle expression of genes involved in mitochondrial biogenesis, energy metabolism and angiogenesis in the Diet+EX group without any change in the Diet-ONLY group. There were no differences between groups in plasma branched-chain amino acids or markers of inflammation, and both interventions caused similar changes in the gut microbiome. These results demonstrate that adding regular exercise to a diet-induced weight loss program has profound metabolic benefits in people with obesity and prediabetes.
2023-04-26 | GSE230002 | GEO
Project description:Background: Diet induced weight reduction promotes a decrease in resting energy expenditure that could partly explain the difficulty to maintain reduced body mass. Whether this reduction remains after stabilized weight loss is still controversial. The molecular mechanisms are unknown. Objective: To investigate the effect of a stabilized 10%-weight loss on resting metabolic rate, body composition and skeletal muscle gene expression profile in obese women. Design: Obese women were successively submitted to a 4-w very low-calorie diet, a 3-6-wk low-calorie diet, and a 4-wk weight maintenance program to achieve a 10% weight loss. Resting energy expenditure, body composition, plasma parameters and skeletal muscle transcriptome were compared before weight loss and during stabilized weight reduction. Results: Energy restriction caused an 11% weight loss. Stabilization to the new weight was accompanied by an 11% decrease of the resting metabolic rate normalized to the body cellular mass which was below that of lean subjects. The range of the changes in the skeletal muscle transcriptome was modest. The main regulated genes were that of slow/oxidative fiber markers which were overexpressed and the gene encoding the glucose metabolism inhibitor PDK4 which was down-regulated. The knowledge based approach, gene set enrichment analysis, identified pathways related to insulin and interleukin 6 and long term calorie restriction adaptations during weight loss. Set of arrays that are part of repeated experiments Keywords: Biological Replicate
2008-03-26 | GSE9917 | GEO
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
2018-03-27 | GSE112307 | GEO
Project description:In utero undernutrition is associated with obesity and insulin resistance, although its effect on skeletal muscle remains poorly defined. We report that, in mice, adult offspring from undernourished dams have decreased energy expenditure, decreased skeletal muscle mitochondrial content, and altered energetics in isolated mitochondria and permeabilized muscle fibers. Strikingly, when these mice are put on a 40% calorie restricted diet they lose half as much weight as calorie restricted controls. Our results reveal for the first time that in utero undernutrition alters metabolic physiology having a profound effect on skeletal muscle energetics and response to calorie restriction in adulthood. We have used a mouse model of low birth weight generated through 50% food restriction of mouse dams during the third week of gestation. We have studied in utero food restricted offspring and control offspring that were not food restricted in utero in both the ad libitum and calorie restricted states. Gene expression profiling was performed on tibialis anterior muscle from 8 mice per group, pooled in pairs.
2014-08-01 | E-GEOD-53520 | biostudies-arrayexpress
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)
2009-11-04 | E-GEOD-18897 | biostudies-arrayexpress
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. A spectrum of variables from lifestyle factors, gut microbiota and host multi-omics most associated with insulin sensitivity was identified. These analyses highlight associations between variations in insulin sensitivity, serum branched chain amino acids, sAT genes involved in endoplasmic reticulum stress and ubiquitination, and gut metagenomic species. This work has enhanced previous knowledge on mechanistic links between host glucose homeostasis, lifestyle factors and microbiota, and has identified modifiable factors and biomarkers that may be used to predict and improve individual response to weight loss interventions.
2021-02-11 | MTBLS653 | MetaboLights
Project description:In utero undernutrition is associated with obesity and insulin resistance, although its effect on skeletal muscle remains poorly defined. We report that, in mice, adult offspring from undernourished dams have decreased energy expenditure, decreased skeletal muscle mitochondrial content, and altered energetics in isolated mitochondria and permeabilized muscle fibers. Strikingly, when these mice are put on a 40% calorie restricted diet they lose half as much weight as calorie restricted controls. Our results reveal for the first time that in utero undernutrition alters metabolic physiology having a profound effect on skeletal muscle energetics and response to calorie restriction in adulthood.
2014-08-01 | GSE53520 | GEO
Project description:OBJECTIVE Diet intervention in obese adults is the first strategy to induce weight loss and to improve insulin sensitivity. We hypothesized that improvements in insulin sensitivity after weight loss from a short-term dietary intervention tracks with alterations in expression of metabolic genes and abundance of specific lipid species. RESEARCH DESIGN AND METHODS Eight obese, insulin resistant, non-diabetic adults were recruited to participate in a three-week low calorie diet intervention study (1000 kcal/day). Fasting blood samples and vastus lateralis skeletal muscle biopsies were obtained before and after the dietary intervention. Clinical chemistry and measures of insulin sensitivity were determined. Unbiased microarray gene expression and targeted lipidomic analysis of skeletal muscle was performed. RESULTS Body weight was reduced, insulin sensitivity (HOMA-IR) was enhanced, and serum insulin concentration and blood lipid (triglyceride, cholesterol, LDL and HDL) levels were improved after dietary intervention. Gene set enrichment analysis of skeletal muscle revealed that oxidative phosphorylation and inflammatory processes were among the most enriched KEGG-pathways identified after dietary intervention. mRNA expression of PDK4 and MLYCD increased, while SCD decreased in skeletal muscle after dietary intervention. Dietary intervention altered the intramuscular lipid profile of skeletal muscle, with changes in content of phosphatidylcholine and triglyceride species among the pronounced. CONCLUSIONS Short-term diet intervention and weight loss in obese adults alters metabolic gene expression and reduces specific phosphatidylcholine and triglyceride species in skeletal muscle, concomitant with improvements in clinical outcomes and enhanced insulin sensitivity.
2019-02-05 | GSE103682 | GEO
Project description:Subcutaneous adipose tissue transcriptomes were compared between 21 obese individuals that either maintained weight loss (good controllers) or regained weight (poor controllers) during a 2-phase dietary Intervention. Dietary intervention: Individuals underwent 8-weeks of calorie-restriction, then 6-months of ad libitum diet.
2017-07-21 | GSE95624 | GEO