Changes in the transcriptome of abdominal subcutaneous adipose tissue in response to short-term overfeeding in lean and obese men

Background: Obesity is caused by the excessive accumulation of adipose tissue as a result of a chronic energy surplus. Little is known regarding the molecular mechanisms involved in the response to an energy surplus in human adipose tissue at the genomic level. Objective: The objective was to investigate changes in the transcriptome of abdominal subcutaneous adipose tissue after a positive energy challenge induced by overfeeding in both lean and obese subjects to identify novel obesity candidate genes. Design: A total of 26 men were recruited and classified on the basis of percentage body fat ( measured by dual-energy X-ray absorptiometry) as lean (<20%) or obese (>25%) to participate in the baseline comparison. Sixteen men participated in the overfeeding study ( 8 lean and 8 obese). Adipose tissue biopsy samples were collected from all subjects at the subumbilical region. Global gene expression profiles were determined at baseline and after a 7-d hypercaloric diet at 40% above normal energy requirements by using whole human genome DNA microarrays. Results: Overfeeding induced differential expression in 45 genes. Six genes displayed a significant interaction effect between adiposity status and overfeeding treatment, including transferrin (TF), stearoyl-CoA desaturase (SCD), transaldolase 1 (TALDO1), cathepsin C (CTSC), insulin receptor substrate 2 (IRS2), and pyruvate dehydrogenase kinase, isozyme 4 (PDK4). Overfeeding resulted in changes in expression of these genes in lean subjects, whereas no significant changes were evident in obese subjects. Conclusions: Differential expression of these 6 genes may represent a protective mechanism at the molecular level in lean subjects in response to an energy surplus. These genes represent valuable candidates for downstream studies related to obesity. Am J Clin Nutr 2009; 89: 407-15.