PLoS ONE (Jan 2016)

DNA Methylation Suppresses Leptin Gene in 3T3-L1 Adipocytes.

  • Masashi Kuroda,
  • Ayako Tominaga,
  • Kasumi Nakagawa,
  • Misa Nishiguchi,
  • Mayu Sebe,
  • Yumiko Miyatake,
  • Tadahiro Kitamura,
  • Rie Tsutsumi,
  • Nagakatsu Harada,
  • Yutaka Nakaya,
  • Hiroshi Sakaue

DOI
https://doi.org/10.1371/journal.pone.0160532
Journal volume & issue
Vol. 11, no. 8
p. e0160532

Abstract

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Leptin is a key regulator of energy intake and expenditure. This peptide hormone is expressed in mouse white adipose tissue, but hardly expressed in 3T3-L1 adipocytes. Using bisulfite sequencing, we found that CpG islands in the leptin promoter are highly methylated in 3T3-L1cells. 5-azacytidine, an inhibitor of DNA methyltransferase, markedly increased leptin expression as pre-adipocytes matured into adipocytes. Remarkably, leptin expression was stimulated by insulin in adipocytes derived from precursor cells exposed to 5-azacytidine, but suppressed by thiazolidinedione and dexamethasone. In contrast, adipocytes derived from untreated precursor cells were unresponsive to both 5-azacytidine and hormonal stimuli, although lipid accumulation was sufficient to boost leptin expression in the absence of demethylation. Taken together, the results suggest that leptin expression in 3T3-L1 cells requires DNA demethylation prior to adipogenesis, transcriptional activation during adipogenesis, and lipid accumulation after adipogenesis.