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
Affiliations
- Yiran Zheng
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Yiran Zheng
- Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Luisa Sophie Rajcsanyi
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Luisa Sophie Rajcsanyi
- Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Manuela Kowalczyk
- Department of Endocrinology, Diabetes and Metabolism and Clinical Chemistry – Division of Laboratory Research, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Johanna Giuranna
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Beate Herpertz-Dahlmann
- Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of the RWTH Aachen, Aachen, Germany
- Jochen Seitz
- Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of the RWTH Aachen, Aachen, Germany
- Martina de Zwaan
- Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany
- Wolfgang Herzog
- Department of Internal Medicine II, General Internal and Psychosomatic Medicine, University of Heidelberg, Heidelberg, Germany
- Stefan Ehrlich
- Translational Developmental Neuroscience Section, Department of Child and Adolescent Psychiatry, TU-Dresden, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
- Stefan Ehrlich
- Eating Disorders Research and Treatment Center, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany
- Stephan Zipfel
- Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital, Tübingen, Germany
- Stephan Zipfel
- 0Centre of Excellence for Eating Disorders, University of Tübingen, Tübingen, Germany
- Katrin Giel
- Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital, Tübingen, Germany
- Katrin Giel
- 0Centre of Excellence for Eating Disorders, University of Tübingen, Tübingen, Germany
- Karin Egberts
- 1Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
- Roland Burghardt
- 2Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Oberberg Fachklinik Fasanenkiez, Berlin, Germany
- Manuel Föcker
- 3Department of Child and Adolescent Psychiatry, University of Münster, Münster, Germany
- Saad Al-Lahham
- 4Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
- Johannes Hebebrand
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Johannes Hebebrand
- Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Dagmar Fuhrer
- Department of Endocrinology, Diabetes and Metabolism and Clinical Chemistry – Division of Laboratory Research, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Dagmar Fuhrer
- 5Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Susanne Tan
- 5Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Denise Zwanziger
- Department of Endocrinology, Diabetes and Metabolism and Clinical Chemistry – Division of Laboratory Research, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Triinu Peters
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Triinu Peters
- Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Anke Hinney
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Anke Hinney
- Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- DOI
- https://doi.org/10.3389/fendo.2023.1137308
- Journal volume & issue
-
Vol. 14
Abstract
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.
Keywords