78825 20220525082803.0 doi 10.1038/s41598-019-40482-0 sideral 111148 ART-2019-111148 eng Ruiz-Ojeda, F.J. Effects of X-chromosome Tenomodulin Genetic Variants on Obesity in a Children’s Cohort and Implications of the Gene in Adipocyte Metabolism 2019 Access copy available to the general public Unrestricted Tenomodulin (TNMD) is a type II transmembrane glycoprotein that has been recently linked to obesity, and it is highly expressed in obese adipose tissue. Several sex-dependent associations have been observed between single-nucleotide polymorphisms (SNPs) of the TNMD gene, which is located in the X-chromosome, and obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome in adults. On the other hand, results are lacking for children. We aimed (i) to study the association between TNMD genetic variants and metabolic complications related to childhood obesity and (ii) to investigate the function of TNMD in human adipocytes. We conducted a case-control, multicenter study in 915 Spanish children and demonstrated significant positive associations between TNMD genetic variants and BMI z-score, waist circumference, fasting glucose, and insulin resistance in boys, highlighting the SNP rs4828038. Additionally, we showed a BMI-adjusted inverse association with waist circumference in girls. Second, in vitro experiments revealed that TNMD is involved in adipogenesis, along with glucose and lipid metabolism in differentiated adipocytes, and these effects may be mediated through AMPK activation. Hence, these results suggest that TNMD genetic variants could be potentially useful as early life risk indicators for obesity and T2DM. In addition, we support the fact that TNMD exhibits significant metabolic functions in adipocytes. info:eu-repo/grantAgreement/ES/ISCIII/PI020826 info:eu-repo/grantAgreement/ES/ISCIII/PI051968 info:eu-repo/grantAgreement/ES/ISCIII/PI11-02042 info:eu-repo/grantAgreement/ES/ISCIII/PI16-00871 info:eu-repo/grantAgreement/ES/ISCIII/RETICS-RD12-0026-0015 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.998 2019 MULTIDISCIPLINARY SCIENCES 17 / 71 = 0.239 2019 Q1 T1 1.341 2019 Multidisciplinary 2019 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Anguita-Ruiz, A. Rupérez, A.I. Universidad de Zaragoza (orcid)0000-0002-3850-8235 Gomez-Llorente, C. Olza, J. Vázquez-Cobela, R. Gil-Campos, M. Bueno, G. Universidad de Zaragoza (orcid)0000-0002-0902-387X Leis, R. Cañete, R. Moreno, L.A. Universidad de Zaragoza (orcid)0000-0003-0454-653X Gil, A. Aguilera, C.M. 1006 255 Universidad de Zaragoza Dpto. Fisiatría y Enfermería Área Enfermería 1010 670 Universidad de Zaragoza Dpto. Pediatría Radiol.Med.Fís Área Pediatría 9, 1 (2019), 3979 [16 pp] Sci. rep. Scientific Reports 2045-2322 897030 http://zaguan.unizar.es/record/78825/files/texto_completo.pdf Versión publicada 109588 http://zaguan.unizar.es/record/78825/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:78825 articulos driver 2022-05-25-08:24:12 ARTICLE