Статья

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

Armand ValsesiaNestlé Institute of Health Sciences, 1015, Lausanne, Switzerland. [email protected]Qiao‐Ping WangFunctional Genomics group, Charles Perkins Centre, University of Sydney, 2006, Sydney, NSW, AustraliaNele GheldofNestlé Institute of Health Sciences, 1015, Lausanne, SwitzerlandJérôme CarayolNestlé Institute of Health Sciences, 1015, Lausanne, SwitzerlandHélène RuffieuxEcole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, SwitzerlandTeleri ClarkFunctional Genomics group, Charles Perkins Centre, University of Sydney, 2006, Sydney, NSW, AustraliaVictoria ShentonFunctional Genomics group, Charles Perkins Centre, University of Sydney, 2006, Sydney, NSW, AustraliaLisa J. OystonFunctional Genomics group, Charles Perkins Centre, University of Sydney, 2006, Sydney, NSW, AustraliaGrégory LefebvreNestlé Institute of Health Sciences, 1015, Lausanne, SwitzerlandSylviane MétaironNestlé Institute of Health Sciences, 1015, Lausanne, SwitzerlandChristian ChabertNestlé Institute of Health Sciences, 1015, Lausanne, SwitzerlandOndine WalterNestlé Institute of Health Sciences, 1015, Lausanne, SwitzerlandPolina MironovaNestlé Institute of Health Sciences, 1015, Lausanne, SwitzerlandPaulina LauOttawa Hospital Weight Management Clinic, The Ottawa Hospital, K1Y 4E9, Ottawa, ON, CanadaPatrick DescombesNestlé Institute of Health Sciences, 1015, Lausanne, SwitzerlandNathalie ViguerieInstitute of Metabolic and Cardiovascular Diseases, INSERM, Paul Sabatier University, UMR 1048, Obesity Research Laboratory, University of Toulouse, 31432, Toulouse, FranceDominique LanginDepartment of Clinical Biochemistry, Toulouse University Hospitals, 31432, Toulouse, FranceMary‐Ellen HarperDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, ON, CanadaArne AstrupDepartment of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2200, Copenhagen, DenmarkWim H. M. SarisDepartment of Human Biology, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+(MUMC+), 6211, Maastricht, The NetherlandsRobert DentEcole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, SwitzerlandG. Gregory NeelyFunctional Genomics group, Charles Perkins Centre, University of Sydney, 2006, Sydney, NSW, AustraliaJörg HagerNestlé Institute of Health Sciences, 1015, Lausanne, Switzerland

2019en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1038/s41467-019-08492-8

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar