{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:49:34Z","timestamp":1760147374826,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["209933838","82DZD00601"],"award-info":[{"award-number":["209933838","82DZD00601"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsches Zentrum f\u00fcr Diabetesforschung","award":["209933838","82DZD00601"],"award-info":[{"award-number":["209933838","82DZD00601"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The SNP rs10487505 in the promotor region of the leptin gene was reported to be associated with decreased circulating leptin and increased body mass index (BMI). However, the phenotypic outcomes affected by rs10487505 in the leptin regulatory pathway have not been systematically studied. Therefore, the aim of this study was to elucidate the influence of rs10487505 on leptin mRNA expression and obesity-related parameters. We genotyped rs10487505 in DNA samples from 1665 patients with obesity and lean controls and measured leptin gene expression in paired samples of adipose tissue (AT, N = 310), as well as circulating leptin levels. We confirm the leptin-lowering effect of rs10487505 in women. In contrast to the previously reported data from population-based studies, in this mainly obese cohort, we describe a lower mean BMI in women carrying the C allele of rs10487505. However, no association of rs10487505 with AT leptin mRNA expression was found. Our data suggest that reduced circulating leptin levels are not a result of the direct silencing of leptin mRNA expression. Furthermore, leptin reduction by rs10487505 does not associate with BMI in a linear manner. Instead, the decreasing effect on BMI might be dependent on the severity of obesity.<\/jats:p>","DOI":"10.3390\/genes14020378","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T03:22:47Z","timestamp":1675221767000},"page":"378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex-Specific Effects of the Genetic Variant rs10487505 Upstream of leptin in the Development of Obesity"],"prefix":"10.3390","volume":"14","author":[{"given":"Janine","family":"Molder","sequence":"first","affiliation":[{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9204-5780","authenticated-orcid":false,"given":"Esther","family":"Guiu-Jurado","sequence":"additional","affiliation":[{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany"},{"name":"Deutsches Zentrum f\u00fcr Diabetesforschung e.V., 85764 Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5936-0217","authenticated-orcid":false,"given":"Yusef","family":"Moulla","sequence":"additional","affiliation":[{"name":"Clinic for Visceral, Transplantation and Thorax and Vascular Surgery, University Hospital Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Stroh","sequence":"additional","affiliation":[{"name":"Department of General, Abdominal and Pediatric Surgery, Municipal Hospital, 07548 Gera, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arne","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Clinic for Visceral, Transplantation and Thorax and Vascular Surgery, University Hospital Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Sch\u00f6n","sequence":"additional","affiliation":[{"name":"St\u00e4dtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, 76133 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"St\u00e4dtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, 76133 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Lohmann","sequence":"additional","affiliation":[{"name":"Municipal Clinic Dresden-Neustadt, 01129 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Dressler","sequence":"additional","affiliation":[{"name":"Municipal Clinic Dresden-Neustadt, 01129 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Stumvoll","sequence":"additional","affiliation":[{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany"},{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0290-5423","authenticated-orcid":false,"given":"Peter","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0208-2065","authenticated-orcid":false,"given":"Matthias","family":"Bl\u00fcher","sequence":"additional","affiliation":[{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany"},{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7625-7254","authenticated-orcid":false,"given":"Nora","family":"Kl\u00f6ting","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum M\u00fcnchen at the University of Leipzig and University Hospital Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nature05487","article-title":"Mechanisms linking obesity with cardiovascular disease","volume":"444","author":"Mertens","year":"2006","journal-title":"Nature"},{"key":"ref_2","first-page":"291546","article-title":"Obesity as a major risk factor for cancer","volume":"2013","author":"Silvestris","year":"2013","journal-title":"J. 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