title: DNA Methylation Suppresses Leptin Gene in 3T3-L1 Adipocytes.
abstract: 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.
authors: Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan.|Research Fellow of Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo, Japan.
authors: Masashi
authors: M
authors: Kuroda
authors: Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan.
authors: Ayako
authors: A
authors: Tominaga
authors: Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan.
authors: Kasumi
authors: K
authors: Nakagawa
authors: Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan.
authors: Misa
authors: M
authors: Nishiguchi
authors: Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan.
authors: Mayu
authors: M
authors: Sebe
authors: Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan.
authors: Yumiko
authors: Y
authors: Miyatake
authors: Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan.
authors: Tadahiro
authors: T
authors: Kitamura
authors: Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan.
authors: Rie
authors: R
authors: Tsutsumi
authors: Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan.
authors: Nagakatsu
authors: N
authors: Harada
authors: Cardiovascular Medicine, Shikoku Central Hospital of the Mutual aid Association of Public School Teachers, Shikokuchuo-city, Ehime, Japan.
authors: Yutaka
authors: Y
authors: Nakaya
authors: Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-city, Tokushima, Japan.|Diabetes Therapeutics and Research Center, Tokushima University, Tokushima-city, Tokushima, Japan.
authors: Hiroshi
authors: H
authors: Sakaue
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D020738:Leptin; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D001374:Azacitidine