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

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 a...

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Main Authors: Zheng, Yiran (Author) , Rajcsanyi, Luisa Sophie (Author) , Kowalczyk, Manuela (Author) , Giuranna, Johanna (Author) , Herpertz-Dahlmann, Beate (Author) , Seitz, Jochen (Author) , de Zwaan, Martina (Author) , Herzog, Wolfgang (Author) , Ehrlich, Stefan (Author) , Zipfel, Stephan (Author) , Giel, Katrin (Author) , Egberts, Karin M. (Author) , Burghardt, Roland (Author) , Föcker, Manuel (Author) , Al-Lahham, Saad (Author) , Hebebrand, Johannes (Author) , Fuhrer, Dagmar (Author) , Tan, Susanne (Author) , Zwanziger, Denise (Author) , Peters, Triinu (Author) , Hinney, Anke (Author)
Format: Article (Journal)
Language:English
Published: 21 March 2023
In: Frontiers in endocrinology
Year: 2023, Volume: 14, Pages: 1-12
ISSN:1664-2392
Online Access:Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fendo.2023.1137308
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Author Notes:Yiran Zheng, Luisa Sophie Rajcsanyi, Manuela Kowalczyk, Johanna Giuranna, Beate Herpertz-Dahlmann, Jochen Seitz, Martina de Zwaan, Wolfgang Herzog, Stefan Ehrlich, Stephan Zipfel, Katrin Giel, Karin Egberts, Roland Burghardt, Manuel Föcker, Saad Al-Lahham, Johannes Hebebrand, Dagmar Fuhrer, Susanne Tan, Denise Zwanziger, Triinu Peters and Anke Hinney
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Summary: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 Description:Gesehen am 07.06.2023
Physical Description:Online Resource
ISSN:1664-2392

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