Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Armand Valsesia, Qiao-Ping Wang, Nele Gheldof, Jérôme Carayol, Hélène Ruffieux, Teleri Clark, Victoria Shenton, Lisa J. Oyston, Gregory Lefebvre, Sylviane Metairon, Christian Chabert, Ondine Walter, Polina Mironova, Paulina Lau, Patrick Descombes, Nathalie Viguerie, Dominique Langin, Mary-Ellen Harper, Arne Astrup, Wim H. Saris, Robert Dent, Greg G. Neely, Jörg Hager

ABSTRACT

Hundreds of genetic variants have been associated with Body Mass Index (BMI) through genome-wide association studies (GWAS) using observational cohorts. However, the genetic contribution to efficient weight loss in response to dietary intervention remains unknown. We perform a GWAS in two large low-caloric diet intervention cohorts of obese participants. Two loci close to NKX6.3/MIR486 and RBSG4 are identified in the Canadian discovery cohort (n = 1166) and replicated in the DiOGenes cohort (n = 789). Modulation of HGTX (NKX6.3 ortholog) levels in Drosophila melanogaster leads to significantly altered triglyceride levels. Additional tissue-specific experiments demonstrate an action through the oenocytes, fly hepatocyte-like cells that regulate lipid metabolism. Our results identify genetic variants associated with the efficacy of weight loss in obese subjects and identify a role for NKX6.3 in lipid metabolism, and thereby possibly weight control. More... »

PAGES

540

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-08492-8

    DOI

    http://dx.doi.org/10.1038/s41467-019-08492-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111838211

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30710084


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