The expansion of white adipose tissue (WAT) mass during the development of obesity is mediated in part through an increase in adipocyte size. Although gene expression profiles associated with adipogenesis in vitro and the development of obesity in vivo have been characterized by DNA microarray analysis, the role of chromatin and chromatin-modifying proteins in the regulation of gene expression related to adipocyte hypertrophy has remained unclear. We have now shown that maintenance of C57BL/6J mice on a high-fat diet for 16 weeks resulted in marked up-regulation of the expression of leptin, Mest (mesoderm specific transcript; also known as paternally expressed gene 1, or Peg1), and sFRP5 (secreted frizzled-related protein 5) genes in WAT. Furthermore, the demethylating agent 5-aza-2′-deoxycytidine increased the amount of Mest/Peg1 mRNA, but not that of leptin or sFRP5 mRNAs, in mouse 3T3-L1 adipocytes. However, analysis by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry revealed that maintenance of mice on a high-fat diet for various times did not affect the level of methylation at specific CpG sites in the promoter regions of leptin, Mest/Peg1, and sFRP5 genes in WAT. Our results indicate that the diet-induced up-regulation of leptin, Mest/Peg1, and sFRP5 gene expression in WAT during the development of obesity in mice is not mediated directly by changes in DNA methylation.

The worldwide epidemic of obesity is a serious threat to public health, in part because the increase in the mass of white adipose tissue (WAT) in obese individuals increases the risk for development of type 2 diabetes mellitus and cardiovascular disease. The expansion of WAT during the development of obesity occurs as a result of increases in cell number (adipocyte hyperplasia) or in cell size (adipocyte hypertrophy)[1, 2]. Analysis of the changes in gene expression in WAT associated with adipocyte hypertrophy are likely to provide insight into the contribution of this process to obesity and metabolic disorders. Although gene expression profiles of adipocytes during their differentiation in vitro [3] as well as of WAT during the development of obesity in vivo [4] have been characterized with the use of DNA microarrays over the past decade or so, the role of chromatin and chromatin-modifying proteins in the regulation of gene expression during adipogenesis has only become apparent more recently [5].