title: Epigenetic modification of the leptin promoter in diet-induced obese mice and the effects of N-3 polyunsaturated fatty acids.
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.
authors.affiliation: 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].
authors.forename: Wenwen
authors.initials: W
authors.lastname: Shen
authors.affiliation: 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].
authors.forename: Cui
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Lulu
authors.initials: L
authors.lastname: Xia
authors.affiliation: 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.
authors.forename: Chaonan
authors.initials: C
authors.lastname: Fan
authors.affiliation: 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.
authors.forename: Hua
authors.initials: H
authors.lastname: Dong
authors.affiliation: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Deckelbaum
authors.affiliation: 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.
authors.forename: Kemin
authors.initials: K
authors.lastname: Qi
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D018899:CpG Islands / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008745:Methylation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects; D012319:RNA Polymerase II / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004268:DNA-Binding Proteins; D015525:Fatty Acids, Omega-3; D006657:Histones; D020738:Leptin; C489326:Mbd2 protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases; D012319:RNA Polymerase II; D006655:Histone Deacetylases