早期设置的POMC甲基化变异性伴随着肥胖风险的增加,并且可以通过MC4R激素治疗来解决
Lara Lechner1, Robert Opitz2, Matt J Silver3
1Department of Pediatric Endocrinology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany.
Science translational medicine
|July 19, 2023
概括
亲opiomelanocortin (POMC) 基因的表观遗传变化与肥胖风险有关. 这种在发育早期确定的表观遗传变体是用MC4R激动剂向的,导致肥胖个体显著减肥.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 代谢障碍 代谢障碍 代谢障碍
- 神经内分泌学神经内分泌学
背景情况:
- 表观遗传变异越来越多地被认为是肥胖的危险因素.
- 亲opiomelanocortin (POMC) 基因在调节腹感方面发挥着至关重要的作用.
- POMC的DNA甲基化模式与肥胖症的发展有关.
研究的目的:
- 为了研究POMC基因DNA甲基化在肥胖中的作用.
- 探索POMC甲基化状态的早期胚胎建立.
- 评估MC4R激应剂在POMC高甲基化肥胖个体中的治疗潜力.
主要方法:
- 对肥胖个体POMC基因中DNA甲基化的分析.
- 建立和分化人类胚胎干细胞 (hESC) 模型,以研究POMC甲基化.
- 用MC4R激动剂治疗POMC高甲基化肥胖个体的治疗.
主要成果:
- 性别特定的非遗传性POMC高甲基化与肥胖风险增加1.4倍有关.
- 在hESCs分化成下丘脑神经元时,POMC甲基化模式被重新建立.
- 减少POMC基因表达与增加POMC表达神经元中的POMC甲基化相关.
- 在患有POMC高甲基化症的肥胖个体中,使用MC4R激素治疗导致平均体重减少4.66%.
结论:
- 在POMC基因中发现了一种表观遗传肥胖风险变异,符合胚胎早期发育过程中建立的转移性类基因的标准.
- 这种POMC表观遗传变化可能可以通过MC4R激素治疗来向,以减少肥胖个体的体重.
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