Contribution of Energy Restriction and Macronutrient Composition to Changes in Adipose Tissue Gene Expression during Dietary Weight-Loss Programs in Obese Women

Context: Hypoenergetic diets are used to reduce body fat mass and metabolic risk factors in obese subjects. The molecular changes in adipose tissue associated with weight loss and specifically related to the dietary composition are poorly understood. Objective: We investigated adipose tissue gene expression from human obese women according to energy deficit and the fat and carbohydrate content of the diet. Design and Setting: Obese subjects recruited among eight European clinical centers were followed up 10 wk of either a low-fat (high carbohydrate) or a moderate-fat (low carbohydrate) hypoenergetic diet. Subjects: Two sets of 47 women in each dietary arm were selected among 648 subjects matched for anthropometric and biological parameters. Main Outcome Measure: We measured adipose tissue gene expression changes in one set using a candidate gene approach. The other set was used to survey 24,469 transcripts using DNA microarrays. Results were analyzed using dedicated statistical methods. Diet-sensitive regulations were confirmed on the other set of subjects. Results: The two diets induced similar weight loss and similar changes for most of the biological variables except for components of the blood lipid profile. One thousand genes were regulated by energy restriction. We validated an effect of the fat to carbohydrate ratio for five genes (FABP4, NR3C1, SIRT3, FNTA, and GABARAPL2) with increased expression during the moderate-fat diet. Conclusions: Energy restriction had a more pronounced impact on variations in human adipose tissue gene expression than macronutrient composition. The macronutrient-sensitive regulation of a subset of genes may influence adipose tissue function and metabolic response. (J Clin Endocrinol Metab 93: 4315-4322, 2008)