Diet-induced up-regulation of gene expression in adipocytes without changes in DNA methylation.
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.
Okada
Yuko
Y
Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Sakaue
Hiroshi
H
Nagare
Tomoki
T
Kasuga
Masato
M
D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing; D052438:Adipocytes, White / Q000378:metabolism* / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine / Q000031:analogs & derivatives; D048429:Cell Size; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D004041:Dietary Fats / Q000009:adverse effects; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000094742:Secreted Frizzled-Related Proteins
D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine; D000077209:Decitabine; D004041:Dietary Fats; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D011506:Proteins; C487972:Sfrp5 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C103637:mesoderm specific transcript protein