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.