Promoter specific DNA methylation and gene expression of POMC in acutely underweight and recovered patients with anorexia nervosa.
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.
Ehrlich
Stefan
S
Charité - Universitätsmedizin Berlin, CVK, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Berlin, Germany. stefan@nmr.mgh.harvard.edu
Weiss
Deike
D
Burghardt
Roland
R
Infante-Duarte
Carmen
C
Brockhaus
Simone
S
Muschler
Marc A
MA
Bleich
Stefan
S
Lehmkuhl
Ulrike
U
Frieling
Helge
H
D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D015992:Body Mass Index; D001835:Body Weight; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D020738:Leptin / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D044342:Malnutrition / Q000097:blood / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013851:Thinness / Q000097:blood / Q000235:genetics*; D055815:Young Adult; D000521:alpha-MSH / Q000235:genetics / Q000378:metabolism
D020738:Leptin; D012333:RNA, Messenger; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin