DNA Methylation Suppresses Leptin Gene in 3T3-L1 Adipocytes

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...

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Published in:PloS one 2016-08, Vol.11 (8), p.e0160532-e0160532
Main Authors: Kuroda, Masashi, Tominaga, Ayako, Nakagawa, Kasumi, Nishiguchi, Misa, Sebe, Mayu, Miyatake, Yumiko, Kitamura, Tadahiro, Tsutsumi, Rie, Harada, Nagakatsu, Nakaya, Yutaka, Sakaue, Hiroshi
Format: Article
Language:English
Subjects:
3T3-L1 Cells - drug effects
Accumulation
Adipocytes
Adipocytes - physiology
Adipogenesis
Adipose tissue
Animals
Azacitidine - pharmacology
Azacytidine
Biology and life sciences
Bisulfite
CpG islands
Demethylation
Deoxyribonucleic acid
Dexamethasone
Diabetes
DNA
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA methylation
DNA Methylation - drug effects
DNA methyltransferase
Energy intake
Gene expression
Gene Expression Regulation - drug effects
Genetic aspects
Genetic engineering
Influence
Insulin
Leptin
Leptin - genetics
Leptin - metabolism
Male
Medicine and Health Sciences
Metabolism
Methylation
Mice
Mice, Inbred C57BL
Nutrition
Obesity
Obesity - metabolism
Physiological aspects
Plasmids
Promoter Regions, Genetic
Rodents
Transcription activation
University graduates
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0160532