{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:29:14Z","timestamp":1768868954020,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","doi-asserted-by":"publisher","award":["209933838"],"award-info":[{"award-number":["209933838"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","doi-asserted-by":"publisher","award":["82DZD00601"],"award-info":[{"award-number":["82DZD00601"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsches Zentrum f\u00fcr Diabetesforschung","award":["209933838"],"award-info":[{"award-number":["209933838"]}]},{"name":"Deutsches Zentrum f\u00fcr Diabetesforschung","award":["82DZD00601"],"award-info":[{"award-number":["82DZD00601"]}]},{"name":"China Scholarship Council","award":["209933838"],"award-info":[{"award-number":["209933838"]}]},{"name":"China Scholarship Council","award":["82DZD00601"],"award-info":[{"award-number":["82DZD00601"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>GRB14\/COBLL1 locus has been shown to be associated with body fat distribution (FD), but neither the causal gene nor its role in metabolic diseases has been elucidated. We hypothesize that GRB14\/COBLL1 may act as the causal genes for FD-related SNPs (rs10195252 and rs6738627), and that they may be regulated by SNP to effect obesity-related metabolic traits. We genotyped rs10195252 and rs6738627 in 2860 subjects with metabolic phenotypes. In a subgroup of 560 subjects, we analyzed GRB14\/COBLL1 gene expression in paired visceral and subcutaneous adipose tissue (AT) samples. Mediation analyses were used to determine the causal relationship between SNPs, AT GRB14\/COBLL1 mRNA expression, and obesity-related traits. In vitro gene knockdown of Grb14\/Cobll1 was used to test their role in adipogenesis. Both gene expressions in AT are correlated with waist circumference. Visceral GRB14 mRNA expression is associated with FPG and HbA1c. Both SNPs are associated with triglycerides, FPG, and leptin levels. Rs10195252 is associated with HbA1c and seems to be mediated by visceral AT GRB14 mRNA expression. Our data support the role of the GRB14\/COBLL1 gene expression in body FD and its locus in metabolic sequelae: in particular, lipid metabolism and glucose homeostasis, which is likely mediated by AT GRB14 transcript levels.<\/jats:p>","DOI":"10.3390\/ijms23158558","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T21:41:37Z","timestamp":1659476497000},"page":"8558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Metabolic Effects of the Waist-To-Hip Ratio Associated Locus GRB14\/COBLL1 Are Related to GRB14 Expression in Adipose Tissue"],"prefix":"10.3390","volume":"23","author":[{"given":"Chang","family":"Sun","sequence":"first","affiliation":[{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franz","family":"F\u00f6rster","sequence":"additional","affiliation":[{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Gutsmann","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\/0000-0002-5936-0217","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":"Departement of Obesity and Metabolic Surgery, SRH Wald-Klinikum Gera Str.d. Friedens 122, 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\/0000-0003-0208-2065","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\/0000-0002-0290-5423","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"}]},{"given":"Jana","family":"Breitfeld","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\/0000-0001-9204-5780","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":"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"},{"name":"Deutsches Zentrum f\u00fcr Diabetesforschung e.V., 85764 Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJMra1514009","article-title":"Mechanisms, Pathophysiology, and Management of Obesity","volume":"376","author":"Heymsfield","year":"2017","journal-title":"N. 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