Determinants of human adipose tissue gene expression: impact of diet, sex, metabolic status, and cis genetic regulation

Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT) are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification of environmental and individual factors controlling AT adaptation is therefore essential. Here, expression of 271 transcripts, selected for regulation according to obesity and weight changes, was determined in 515 individuals before, after 8-week low-calorie diet-induced weight loss, and after 26-week ad libitum weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently controlled AT gene expression. These analyses help understanding the relative importance of environmental and individual factors that control the expression of human AT genes and therefore may foster strategies aimed at improving AT function in metabolic diseases

Adipose Tissue CIDEA Is Associated, Independently of Weight Variation, to Change in Insulin Resistance during a Longitudinal Weight Control Dietary Program in Obese Individuals

AIM: Weight loss reduces risk factors associated with obesity. However, long-term metabolic improvement remains a challenge. We investigated quantitative gene expression of subcutaneous adipose tissue in obese individuals and its relationship with low calorie diet and long term weight maintenance induced changes in insulin resistance. RESEARCH DESIGN: Three hundred eleven overweight and obese individuals followed a dietary protocol consisting of an 8-week low calorie diet followed by a 6-month ad libitum weight-maintenance diet. Individuals were clustered according to insulin resistance trajectories assessed using homeostasis model assessment of insulin resistance (HOMA-IR) index. Adipose tissue mRNA levels of 267 genes selected for regulation according to obesity, metabolic status and response to dieting was assessed using high throughput RT-qPCR. A combination of discriminant analyses was used to identify genes with regulation according to insulin resistance trajectories. Partial correlation was used to control for change in body mass index. RESULTS: Three different HOMA-IR profile groups were determined. HOMA-IR improved during low calorie diet in the 3 groups. At the end of the 6-month follow-up, groups A and B had reduced HOMA-IR by 50%. In group C, HOMA-IR had returned to baseline values. Genes were differentially expressed in the adipose tissue of individuals according to groups but a single gene, CIDEA, was common to all phases of the dietary intervention. Changes in adipose tissue CIDEA mRNA levels paralleled variations in insulin sensitivity independently of change in body mass index. Overall, CIDEA was up-regulated in adipose tissue of individuals with successful long term insulin resistance relapse and not in adipose tissue of unsuccessful individuals. CONCLUSION: The concomitant change in adipose tissue CIDEA mRNA levels and insulin sensitivity suggests a beneficial role of adipose tissue CIDEA in long term glucose homeostasis, independently of weight variation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00390637

Seven-day overfeeding enhances adipose tissue dietary fatty acid storage and decreases myocardial and muscle dietary fatty acid partitioning in healthy subjects

International audienceBACKGROUND: Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left-ventricular (LV) function is associated with insulin resistance in prediabetes. OBJECTIVE: We hypothesized that enhanced myocardial DFA partitioning and reduced LV function may be induced concomitantly with reduced insulin sensitivity upon a 7-day hypercaloric (+50% in caloric intake), high saturated fat (~11% of energy) and simple carbohydrates (~54% of energy) diet (HIGHCAL) vs. an isocaloric diet (ISOCAL) with a moderate amount of saturated fat (~8% of energy) and carbohydrates (~50% of energy). DESIGN: Thirteen healthy subjects (7 men/6 women) underwent HIGHCAL vs. ISOCAL in a randomized crossover design, with organ-specific DFA partitioning and LV function measured using the oral 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid and [(11)C]-acetate positron emission tomography methods at the end of both interventions. RESULTS: HIGHCAL induced a decrease in insulin sensitivity indexes with no significant change in body composition. HIGHCAL led to increased subcutaneous abdominal (+4.2+/-1.6 %, P\textless0.04) and thigh (+2.4+/-1.2 %, P\textless0.08) adipose tissue storage and reduced cardiac (-0.31+/-0.11 mean standard uptake value [SUV], P\textless0.03) and skeletal muscle (-0.17+/-0.08 SUV, P\textless0.05) DFA partitioning without change in LV function. CONCLUSIONS: We conclude that early increase in adipose tissue DFA storage protects the heart and skeletal muscles from potential deleterious effects of DFA

Determinants of human adipose tissue gene expression: impact of diet, sex, metabolic status, and cis genetic regulation

Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT) are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification of environmental and individual factors controlling AT adaptation is therefore essential. Here, expression of 271 transcripts, selected for regulation according to obesity and weight changes, was determined in 515 individuals before, after 8-week low-calorie diet-induced weight loss, and after 26-week ad libitum weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently controlled AT gene expression. These analyses help understanding the relative importance of environmental and individual factors that control the expression of human AT genes and therefore may foster strategies aimed at improving AT function in metabolic diseases