Scientific Publications Database
Article Title: Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolismAuthors: Valsesia, Armand; Wang, Qiao-Ping; Gheldof, Nele; Carayol, Jerome; Ruffieux, Helene; Clark, Teleri; Shenton, Victoria; Oyston, Lisa J.; Lefebvre, Gregory; Metairon, Sylviane; Chabert, Christian; Walter, Ondine; Mironova, Polina; Lau, Paulina; Descombes, Patrick; Viguerie, Nathalie; Langin, Dominique; Harper, Mary-Ellen; Astrup, Arne; Saris, Wim H.; Dent, Robert; Neely, Greg G.; Hager, Joerg
Journal: NATURE COMMUNICATIONS Volume 10
Date of Publication:2019
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.