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Sci Rep. 2014 Jun 13;4:5282. doi: 10.1038/srep05282.

Epigenetic modification of the leptin promoter in diet-induced obese mice and the effects of N-3 polyunsaturated fatty acids.

Author information

1
1] Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. No. 56 Nan-li-shi Road, Beijing 100045, China [2].
2
Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. No. 56 Nan-li-shi Road, Beijing 100045, China.
3
Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, USA.

Abstract

We report evidence of a detailed epigenetic modification of the leptin promoter and the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), which is closely associated with the leptin gene transcription in obesity. In the adipose tissue of diet induced obese (DIO) mice, methylation of the CpG island and the binding of methyl-CpG-binding domain protein 2 (MBD2) and DNA methyltransferases (DNMTs) at the leptin promoter are increased and RNA Pol II is decreased. Additionally, histones H3 and H4 are hypoacetylated, lysine 4 of histone H3 (H3K4) is hypomethylated and the binding of histone deacetylases (HDACs) 1, 2 and 6 is increased at the leptin promoter in the DIO mice. These modifications may serve a feedback role to maintain leptin concentrations within a normal range. The regulation of leptin transcriptional expression by n-3 PUFAs is mediated, at least in part, by epigenetic targets, such as MBD2 and histone modifications.

PMID:
24923522
PMCID:
PMC5381469
DOI:
10.1038/srep05282
[Indexed for MEDLINE]
Free PMC Article

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