Time-specific changes in DNA methyltransferases associated with the leptin promoter during the development of obesity.

Autor: Xia L; Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, 100045 Beijing. China.. qikemin@bch.com.cn., Wang C; Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, 100045 Beijing. China.. qikemin@bch.com.cn., Lu Y; Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, 100045 Beijing. China.. qikemin@bch.com.cn., Fan C; Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, 100045 Beijing. China.. qikemin@bch.com.cn., Ding X; Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, 100045 Beijing. China.. qikemin@bch.com.cn., Fu H; Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, 100045 Beijing. China.. qikemin@bch.com.cn., Qi K; Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, 100045 Beijing. China.. qikemin@bch.com.cn.
Jazyk: angličtina
Zdroj: Nutricion hospitalaria [Nutr Hosp] 2014 Dec 01; Vol. 30 (6), pp. 1248-55. Date of Electronic Publication: 2014 Dec 01.
DOI: 10.3305/nh.2014.30.6.7843
Abstrakt: Objective: The role of epigenetic modifications on leptin expression during the development of obesity has not been clearly determined. This study aimed to investigate changes in the expression of DNA methyltransferases (DNMTs) at the leptin promoter and their effect on gene transcription during the development of obesity.
Methods: Using a high-fat diet (HFD)-induced obese (DIO) mouse model, we examined adipose expression of leptin, its promoter associated DNMTs and the methyl CpG-binding domain protein 2 (MBD2) at different time points after HFD feeding.
Results: The leptin expression levels in epididymal fat were significantly increased after feeding the mice a HFD for 4, 8, 12 and 18 weeks (w), as opposed to feeding them a standard diet (SD). However, the CpG promoter methylation fractions were significantly reduced at 8 w with a decreased association of MBD2 and DNMT1, and increased at 12 w and 18 w with an increased association of MBD2, DNMT3A and DNMT3B, after HFD feeding. Additionally, the binding of RNA polymerase II was increased at 8 w and decreased at 18 w after HFD feeding compared with SD feeding.
Conclusions: These data indicate that time-specific changes in promoter associated DNMTs may be associated with the regulation of leptin expression, indicating that a complex and dynamic epigenetic mechanism underlies aberrant leptin expression during the development of obesity.
(Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)
Databáze: MEDLINE
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