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Valsesia, Armand; Wang, Qiao-Ping; Gheldof, Nele; Carayol, Jérôme; Ruffieux, Hélène; 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, Jörg
Nature communications, 02/2019, Letnik: 10, Številka: 1Journal Article
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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in: SICRIS
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