Identification of adipocyte genes regulated by caloric intake.

CONTEXT Changes in energy intake have marked and rapid effects on metabolic functions, and some of these effects may be due to changes in adipocyte gene expression that precede alterations in body weight. OBJECTIVE The aim of the study was to identify adipocyte genes regulated by changes in caloric intake independent of alterations in body weight. RESEARCH DESIGN AND METHODS Obese subjects given a very low-caloric diet followed by gradual reintroduction of ordinary food and healthy subjects subjected to overfeeding were investigated. Adipose tissue biopsies were taken at multiple time-points, and gene expression was measured by DNA microarray. Genes regulated in the obese subjects undergoing caloric restriction followed by refeeding were identified using two-way ANOVA corrected with Bonferroni. From these, genes regulated by caloric restriction and oppositely during the weight-stable refeeding phase were identified in the obese subjects. The genes that were also regulated, in the same direction as the refeeding phase, in the healthy subjects after overfeeding were defined as being regulated by caloric intake. Results were confirmed using real-time PCR or immunoassay. RESULTS Using a significance level of P < 0.05 for all comparisons, 52 genes were down-regulated, and 50 were up-regulated by caloric restriction and regulated in the opposite direction by refeeding and overfeeding. Among these were genes involved in lipogenesis (ACLY, ACACA, FASN, SCD), control of protein synthesis (4EBP1, 4EBP2), β-oxidation (CPT1B), and insulin resistance (PEDF, SPARC). CONCLUSIONS Metabolic genes involved in lipogenesis, protein synthesis, and insulin resistance are central in the transcriptional response of adipocytes to changes in caloric intake.