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

Author

Listed:
  • Armand Valsesia

    (Nestlé Institute of Health Sciences)

  • Qiao-Ping Wang

    (Functional Genomics group, Charles Perkins Centre, University of Sydney
    School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University)

  • Nele Gheldof

    (Nestlé Institute of Health Sciences)

  • Jérôme Carayol

    (Nestlé Institute of Health Sciences)

  • Hélène Ruffieux

    (Nestlé Institute of Health Sciences
    Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Teleri Clark

    (Functional Genomics group, Charles Perkins Centre, University of Sydney)

  • Victoria Shenton

    (Functional Genomics group, Charles Perkins Centre, University of Sydney)

  • Lisa J. Oyston

    (Functional Genomics group, Charles Perkins Centre, University of Sydney)

  • Gregory Lefebvre

    (Nestlé Institute of Health Sciences)

  • Sylviane Metairon

    (Nestlé Institute of Health Sciences)

  • Christian Chabert

    (Nestlé Institute of Health Sciences)

  • Ondine Walter

    (Nestlé Institute of Health Sciences)

  • Polina Mironova

    (Nestlé Institute of Health Sciences)

  • Paulina Lau

    (Ottawa Hospital Weight Management Clinic, The Ottawa Hospital)

  • Patrick Descombes

    (Nestlé Institute of Health Sciences)

  • Nathalie Viguerie

    (Institute of Metabolic and Cardiovascular Diseases, INSERM, Paul Sabatier University, UMR 1048, Obesity Research Laboratory, University of Toulouse)

  • Dominique Langin

    (Institute of Metabolic and Cardiovascular Diseases, INSERM, Paul Sabatier University, UMR 1048, Obesity Research Laboratory, University of Toulouse
    Toulouse University Hospitals)

  • Mary-Ellen Harper

    (Faculty of Medicine, University of Ottawa)

  • Arne Astrup

    (Faculty of Science, University of Copenhagen)

  • Wim H. Saris

    (Maastricht University Medical Centre+(MUMC+))

  • Robert Dent

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Greg G. Neely

    (Functional Genomics group, Charles Perkins Centre, University of Sydney)

  • Jörg Hager

    (Nestlé Institute of Health Sciences)

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.

Suggested Citation

  • Armand Valsesia & Qiao-Ping Wang & Nele Gheldof & Jérôme Carayol & Hélène Ruffieux & Teleri Clark & Victoria Shenton & Lisa J. Oyston & Gregory Lefebvre & Sylviane Metairon & Christian Chabert & Ondin, 2019. "Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08492-8
    DOI: 10.1038/s41467-019-08492-8
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