Changes in adipose tissue gene expression with energy-restricted diets in obese women.

BACKGROUND The effect of energy restriction and macronutrient composition on gene expression in adipose tissue is not well defined. OBJECTIVE The aim of the study was to investigate the effect of different low-energy diets on gene expression in human adipose tissue. DESIGN Forty obese women were randomly assigned to a moderate-fat, moderate-carbohydrate diet or a low-fat, high-carbohydrate hypoenergetic (-600 kcal/d) diet for 10 wk. Subcutaneous adipose tissue samples were obtained before and after the diet period. High-quality RNA samples were obtained from 23 women at both time points, and these samples were hybridized to microarrays containing the 8500 most extensively described human genes. The results were confirmed by separate messenger RNA measurements. RESULTS Both diets resulted in weight losses of approximately 7.5% of baseline body weight. A total of 52 genes were significantly up-regulated and 44 were down-regulated as a result of the intervention, and no diet-specific effect was observed. No major effect on lipid-specific transcription factors or genes regulating signal transduction, lipolysis, or synthesis of acylglycerols was observed. Most changes were modest (<25% of baseline), but all genes regulating the formation of polyunsaturated fatty acids from acetyl-CoA and malonyl-CoA were markedly down-regulated (35-60% decrease). CONCLUSIONS Macronutrients have a secondary role in changes in adipocyte gene expression after energy-restricted diets. The most striking alteration after energy restriction is a coordinated reduction in the expression of genes regulating the production of polyunsaturated fatty acids.