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

Zheng, Yiran and Rajcsanyi, Luisa Sophie and Kowalczyk, Manuela and Giuranna, Johanna and Herpertz-Dahlmann, Beate and Seitz, Jochen and de Zwaan, Martina and Herzog, Wolfgang and Ehrlich, Stefan and Zipfel, Stephan and Giel, Katrin and Egberts, Karin and Burghardt, Roland and Föcker, Manuel and Al-Lahham, Saad and Hebebrand, Johannes and Fuhrer, Dagmar and Tan, Susanne and Zwanziger, Denise and Peters, Triinu and Hinney, Anke (2023) Lipocalin 2 – mutation screen and serum levels in patients with anorexia nervosa or obesity and in lean individuals. Frontiers in Endocrinology, 14. ISSN 1664-2392

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Context: The bone-derived adipokine lipocalin-2 is relevant for body weight regulation by stimulating the leptin-melanocortin pathway.

Objective: We 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.

Methods: Sanger 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.

Results: Fourteen 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).

Conclusion: Lipocalin-2 levels are positively associated with body mass index (BMI). Single LCN2-variants might have a profound effect on lipocalin-2 levels.

Item Type: Article
Subjects: Eprints STM archive > Mathematical Science
Depositing User: Unnamed user with email admin@eprints.stmarchive
Date Deposited: 06 Jul 2023 04:54
Last Modified: 31 Oct 2023 04:54

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