Effects of X-chromosome Tenomodulin Genetic Variants on Obesity in a Children’s Cohort and Implications of the Gene in Adipocyte Metabolism View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Francisco Javier Ruiz-Ojeda, Augusto Anguita-Ruiz, Azahara I. Rupérez, Carolina Gomez-Llorente, Josune Olza, Rocío Vázquez-Cobela, Mercedes Gil-Campos, Gloria Bueno, Rosaura Leis, Ramón Cañete, Luis A. Moreno, Angel Gil, Concepcion Maria Aguilera

ABSTRACT

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. More... »

PAGES

3979

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-019-40482-0

    DOI

    http://dx.doi.org/10.1038/s41598-019-40482-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112641535

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30850679


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    388 Department of Paediatrics, Reina Sofia University Hospital, Institute Maimónides of Biomedicine Investigation of Córdoba (IMIBIC), University of Córdoba, Avda Menéndez Pidal s/n, 14004, Córdoba, Spain
    389 Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014, Granada, Spain
    390 Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain
    391 rdf:type schema:Organization
    392 https://www.grid.ac/institutes/grid.488737.7 schema:alternateName Instituto de Investigación Sanitaria Aragón
    393 schema:name Growth, Exercise, NUtrition and Development (GENUD) Research Group, Universidad de Zaragoza, Zaragoza, Spain
    394 Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain
    395 Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain
    396 rdf:type schema:Organization
     




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