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 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.

Overview publication

TitleLipocalin 2 – mutation screen and serum levels in patients with anorexia nervosa or obesity and in lean individuals
DateMarch 21st, 2023
Issue nameFrontiers in Endocrinology
Issue numberv14
DOI10.3389/fendo.2023.1137308
AuthorsZheng Y, Rajcsanyi LS, Kowalczyk M, Giuranna J, Herpertz-Dahlmann B, Seitz J, de Zwaan M, Herzog W, Ehrlich S, Zipfel S, Giel K, Egberts K, Burghardt R, Föcker M, Al-Lahham S, Hebebrand J, Fuhrer D, Tan S, Zwanziger D, Peters T & Hinney A
MTGsMTG5
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