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Endocrinol."],"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>The bone-derived adipokine lipocalin-2 is relevant for body weight regulation by stimulating the leptin-melanocortin pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to (i) detect variants in the lipocalin-2 gene (<jats:italic>LCN2<\/jats:italic>) which are relevant for body weight regulation and\/or anorexia nervosa (AN); (ii) describe and characterize the impact of <jats:italic>LCN2<\/jats:italic> and <jats:italic>MC4R<\/jats:italic> variants on circulating lipocalin-2 level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sanger sequencing of the coding region of <jats:italic>LCN2<\/jats:italic> in 284 children and adolescents with severe obesity or 287 patients with anorexia nervosa. <jats:italic>In-silico<\/jats:italic> analyses to evaluate functional implications of detected <jats:italic>LCN2<\/jats: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 <jats:italic>LCN2<\/jats:italic> or <jats:italic>MC4R<\/jats:italic>, and 33 matched controls without NSVs in the two genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fourteen <jats:italic>LCN2<\/jats:italic>-variants (five NSVs) were detected. <jats:italic>LCN2<\/jats: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 <jats:italic>LCN<\/jats: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 (<jats:italic>p<\/jats:italic> = 0.033).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Lipocalin-2 levels are positively associated with body mass index (BMI). Single <jats:italic>LCN2<\/jats:italic>-variants might have a profound effect on lipocalin-2 levels.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1137308","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T06:10:15Z","timestamp":1679379015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Lipocalin 2 \u2013 mutation screen and serum levels in patients with anorexia nervosa or obesity and in lean individuals"],"prefix":"10.3389","volume":"14","author":[{"given":"Yiran","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa Sophie","family":"Rajcsanyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Kowalczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Giuranna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Herpertz-Dahlmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Seitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"de Zwaan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Herzog","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Ehrlich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Zipfel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Giel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Egberts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Burghardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"F\u00f6cker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad","family":"Al-Lahham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Hebebrand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmar","family":"Fuhrer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Zwanziger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Triinu","family":"Peters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anke","family":"Hinney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.087213","article-title":"Energy balance and obesity","volume":"126","author":"Hill","year":"2012","journal-title":"Circulation"},{"key":"B2","first-page":"1","article-title":"Physical status: the use and interpretation of anthropometry. 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