Valsesia, A., Wang, Q.P., Gheldof, N., Carayol, J., Ruffieux, H., Clark, T., Shenton, V., Oyston, L.J., Lefebvre, G., Metairon, S., Chabert, C., Walter, O., Mironova, P., Lau, P., Descombes, P., Viguerie, N., Langin, D., Harper, M.E., Astrup, A., Saris, W.H., Dent, R., Neely, G.G., Hager, J. (2019). Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism.  Nat. Commun. 10(1): 540.

FBrf0241349

Research paper

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.

PMC6358625 (PMC) (EuropePMC)