Differential epigenomic and transcriptomic responses in subcutaneous adipose tissue between low and high responders to caloric restriction

Background: Caloric restriction is recommended for the treatment of obesity, but it is generally characterized by large interindividual variability in responses. The factors affecting the magnitude of weight loss remain poorly understood. Epigenetic factors (ie, heritable but reversible changes to genomic function that regulate gene expression independently of DNA sequence) may explain some of the interindividual variability seen in weight-loss responses. Objective: The objective was to determine whether epigenetics and gene expression changes may play a role in weight-loss responsiveness. Design: Overweight/obese postmenopausal women were recruited for a standard 6-mo caloric restriction intervention. Abdominal subcutaneous adipose tissue biopsy samples were collected before (n = 14) and after (n = 14) intervention, and the epigenomic and transcriptomic profiles of the high and low responders to dieting, on the basis of changes in percentage body fat, were compared by using microarray analysis. Results: Significant DNA methylation differences at 35 loci were found between the high and low responders before dieting, with 3 regions showing differential methylation after intervention. Some of these regions contained genes known to be involved in weight control and insulin secretion, whereas others were localized in known imprinted genomic regions. Differences in gene expression profiles were observed only after dieting, with 644 genes being differentially expressed between the 2 groups. These included genes likely to be involved in metabolic pathways related to angiogenesis and cerebellar long-term depression. Conclusions: These data show that both DNA methylation and gene expression are responsive to caloric restriction and provide new insights about the molecular pathways involved in body weight loss as well as methylation regulation during adulthood. Am J Clin Nutr 20 10;91:309-20.