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

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

JOURNAL=Frontiers in Endocrinology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1137308

DOI=10.3389/fendo.2023.1137308

ISSN=1664-2392

ABSTRACT=<sec><title>Context</title><p>The bone-derived adipokine lipocalin-2 is relevant for body weight regulation by stimulating the leptin-melanocortin pathway.</p></sec><sec><title>Objective</title><p>We aimed to (i) detect variants in the lipocalin-2 gene (<italic>LCN2</italic>) which are relevant for body weight regulation and/or anorexia nervosa (AN); (ii) describe and characterize the impact of <italic>LCN2</italic> and <italic>MC4R</italic> variants on circulating lipocalin-2 level.</p></sec><sec><title>Methods</title><p>Sanger sequencing of the coding region of <italic>LCN2</italic> in 284 children and adolescents with severe obesity or 287 patients with anorexia nervosa. <italic>In-silico</italic> analyses to evaluate functional implications of detected <italic>LCN2</italic> 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 <italic>LCN2</italic> or <italic>MC4R</italic>, and 33 matched controls without NSVs in the two genes.</p></sec><sec><title>Results</title><p>Fourteen <italic>LCN2</italic>-variants (five NSVs) were detected. <italic>LCN2</italic>-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 <italic>LCN</italic>2-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 (<italic>p</italic> = 0.033).</p></sec><sec><title>Conclusion</title><p>Lipocalin-2 levels are positively associated with body mass index (BMI). Single <italic>LCN2</italic>-variants might have a profound effect on lipocalin-2 levels.</p></sec>