DNA methylation of ghrelin and leptin receptors in underweight and recovered patients with anorexia nervosa

Victoria-Luise Batury, Esther Walton, Friederike Tam, Marie-Louis Wronski, Vanessa Buchholz, Helge Frieling, Stefan Ehrlich

Research output: Contribution to journalArticlepeer-review

Abstract

Epigenetic mechanisms, which modulate gene expression, are becoming increasingly important in the research on anorexia nervosa (AN). Patients with AN have difficulties with the perception of hunger even though hormones like high ghrelin and low leptin signal the need for energy intake. Given the prominent role of the growth hormone secretagogue receptor (GHS-R1a) and the leptin receptor (LEPR) in appetite regulation, a dysregulation of the receptors' expression levels, possibly resulting from altered DNA promoter methylation, may contribute to the pathophysiology of AN. Such alterations could be secondary effects of undernutrition (state markers) or biological processes that may play an antecedent, possibly causal, role in the pathophysiology (trait markers). Therefore, the objective of this study was to examine DNA promoter methylation of the GHS-R1a and LEPR gene promoter regions and investigate whether methylation levels are associated with AN symptoms. We studied medication-free underweight patients with acute AN as well as weight-recovered patients and normal-weight, healthy female control subjects. While DNA methylation of the LEPR gene was similar across groups, GHS-R1a promoter methylation was increased in underweight AN compared to healthy controls - a finding which can be interpreted within the framework of the "ghrelin-resistance" hypothesis in AN. The results of the current study suggest for the first time a potential epigenetic mechanism underlying altered GHS-R1a sensitivity or altered ghrelin signaling in acutely underweight AN. If a ghrelin-centered model of AN can be verified, a next step could be the search for a dietary or psychopharmacological modulation at the ghrelin receptor, potentially via epigenetic mechanisms.

Original languageEnglish
Pages (from-to)271-278
Number of pages8
JournalJournal of Psychiatric Research
Volume131
Early online date28 Aug 2020
DOIs
Publication statusPublished - 31 Dec 2020

Keywords

  • Anorexia Nervosa/genetics
  • DNA Methylation
  • Female
  • Humans
  • Receptors, Ghrelin/genetics
  • Receptors, Leptin/genetics
  • Thinness/genetics

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