Q1 · CROSS-FIELD
ArticleOA
Author: Shenton, Victoria ; Descombes, Patrick ; Ruffieux, Hélène ; Oyston, Lisa J ; Chabert, Christian ; Astrup, Arne ; Hager, Jörg ; Saris, Wim H ; Neely, Greg G ; Mironova, Polina ; Dent, Robert ; Harper, Mary-Ellen ; Lau, Paulina ; Viguerie, Nathalie ; Metairon, Sylviane ; Clark, Teleri ; Lefebvre, Gregory ; Carayol, Jérôme ; Langin, Dominique ; Gheldof, Nele ; Valsesia, Armand ; Walter, Ondine ; Wang, Qiao-Ping
AbstractHundreds 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 toNKX6.3/MIR486andRBSG4are identified in the Canadian discovery cohort (n = 1166) and replicated in the DiOGenes cohort (n = 789). Modulation ofHGTX(NKX6.3ortholog) levels inDrosophila melanogasterleads 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 forNKX6.3in lipid metabolism, and thereby possibly weight control.