Charité - Universitätsmedizin Berlin, CVK, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Berlin, Germany.
J Psychiatr Res. 2010 Oct;44(13):827-33. doi: 10.1016/j.jpsychires.2010.01.011. Epub 2010 Feb 21.
Proopiomelanocortin (POMC) and its derived peptides, in particular alpha-MSH, have been shown to play a crucial role in the regulation of hunger, satiety and energy homeostasis. Studies in patients with anorexia nervosa (AN) suggest an abnormal expression of appetite-regulating hormones. Hormone expression levels may be modulated by epigenetic mechanisms, which were recently shown to be implicated in the pathophysiology of eating disorders. We hypothesised that POMC promoter specific DNA methylation and gene expression will be affected by malnutrition and therefore differ in AN patients at distinct stages of the disorder. Promoter specific DNA methylation of the POMC gene and expression of POMC mRNA variants were determined in peripheral blood mononuclear cells (PBMC) of 30 healthy control women (HCW), 31 underweight (acAN) and 30 weight-recovered patients with AN (recAN). Malnutrition was characterized by plasma leptin. Expression of the functionally relevant long POMC mRNA transcript was significantly correlated with leptin levels and higher in acAN compared to recAN and HCW. Expression of the truncated form and mean promoter DNA methylation was similar in all three subgroups. Methylation of single CpG residues in the E2F binding site was inversely related to POMC expression. Our preliminary data on pattern of POMC regulation suggests an association with the underweight state rather than with persisting trait markers of AN. In contrast to POMC expression in the central nervous system, peripheral POMC mRNA expression decreased with malnutrition and hypoleptinemia. This may represent a counterregulatory mechanism as part of the crosstalk between the immune and neuroendocrine systems.
阿片促黑素原（POMC）及其衍生肽，特别是α-MSH，已被证明在调节饥饿、饱腹感和能量平衡方面发挥着关键作用。对神经性厌食症（AN）患者的研究表明，食欲调节激素的表达异常。激素表达水平可能受到表观遗传机制的调节，最近的研究表明，这些机制与进食障碍的病理生理学有关。我们假设 POMC 启动子特异性 DNA 甲基化和基因表达将受到营养不良的影响，因此在 AN 患者不同疾病阶段存在差异。我们在 30 名健康对照女性（HCW）、31 名低体重（acAN）和 30 名体重恢复的 AN 患者（recAN）的外周血单核细胞（PBMC）中测定了 POMC 基因启动子特异性 DNA 甲基化和 POMC mRNA 变体的表达。通过血浆瘦素来描述营养不良。功能相关的长 POMC mRNA 转录物的表达与瘦素水平显著相关，且在 acAN 中高于 recAN 和 HCW。截短形式和平均启动子 DNA 甲基化在所有三个亚组中相似。E2F 结合位点的单个 CpG 残基的甲基化与 POMC 表达呈负相关。我们关于 POMC 调节模式的初步数据表明，它与低体重状态有关，而与持续存在的 AN 特征性标志物无关。与中枢神经系统中的 POMC 表达相反，外周 POMC mRNA 表达随着营养不良和低瘦素血症而减少。这可能代表一种作为免疫和神经内分泌系统之间串扰的一部分的代偿性机制。
