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

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 and Jörg Hager
Additional contact information
Armand Valsesia: Nestlé Institute of Health Sciences
Qiao-Ping Wang: Functional Genomics group, Charles Perkins Centre, University of Sydney
Nele Gheldof: Nestlé Institute of Health Sciences
Jérôme Carayol: Nestlé Institute of Health Sciences
Hélène Ruffieux: Nestlé Institute of Health Sciences
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
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

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08492-8

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