Frontiers in Endocrinology (Mar 2023)

Lipocalin 2 – mutation screen and serum levels in patients with anorexia nervosa or obesity and in lean individuals

  • Yiran Zheng,
  • Yiran Zheng,
  • Luisa Sophie Rajcsanyi,
  • Luisa Sophie Rajcsanyi,
  • Manuela Kowalczyk,
  • Johanna Giuranna,
  • Beate Herpertz-Dahlmann,
  • Jochen Seitz,
  • Martina de Zwaan,
  • Wolfgang Herzog,
  • Stefan Ehrlich,
  • Stefan Ehrlich,
  • Stephan Zipfel,
  • Stephan Zipfel,
  • Katrin Giel,
  • Katrin Giel,
  • Karin Egberts,
  • Roland Burghardt,
  • Manuel Föcker,
  • Saad Al-Lahham,
  • Johannes Hebebrand,
  • Johannes Hebebrand,
  • Dagmar Fuhrer,
  • Dagmar Fuhrer,
  • Susanne Tan,
  • Denise Zwanziger,
  • Triinu Peters,
  • Triinu Peters,
  • Anke Hinney,
  • Anke Hinney

DOI
https://doi.org/10.3389/fendo.2023.1137308
Journal volume & issue
Vol. 14

Abstract

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ContextThe bone-derived adipokine lipocalin-2 is relevant for body weight regulation by stimulating the leptin-melanocortin pathway.ObjectiveWe aimed to (i) detect variants in the lipocalin-2 gene (LCN2) which are relevant for body weight regulation and/or anorexia nervosa (AN); (ii) describe and characterize the impact of LCN2 and MC4R variants on circulating lipocalin-2 level.MethodsSanger sequencing of the coding region of LCN2 in 284 children and adolescents with severe obesity or 287 patients with anorexia nervosa. In-silico analyses to evaluate functional implications of detected LCN2 variants. TaqMan assays for rare non-synonymous variants (NSVs) in additional independent study groups. Serum levels of lipocalin-2 were measured by ELISA in 35 females with NSVs in either LCN2 or MC4R, and 33 matched controls without NSVs in the two genes.ResultsFourteen LCN2-variants (five NSVs) were detected. LCN2-p.Leu6Pro and p.Gly9Val located in the highly conserved signal peptide region may induce functional consequences. The secondary structure change of lipocalin-2 due to LCN2-p.Val89Ile may decrease solubility and results in a low lipocalin-2 level in a heterozygotes carrier (female recovered from AN). Lean individuals had lower lipocalin-2 levels compared to patients with obesity (p = 0.033).ConclusionLipocalin-2 levels are positively associated with body mass index (BMI). Single LCN2-variants might have a profound effect on lipocalin-2 levels.

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