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

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.

SUBMITTER: Valsesia A

PROVIDER: S-EPMC6358625 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Valsesia Armand A Wang Qiao-Ping QP Gheldof Nele N Carayol Jérôme J Ruffieux Hélène H Clark Teleri T Shenton Victoria V Oyston Lisa J LJ Lefebvre Gregory G Metairon Sylviane S Chabert Christian C Walter Ondine O Mironova Polina P Lau Paulina P Descombes Patrick P Viguerie Nathalie N Langin Dominique D Harper Mary-Ellen ME Astrup Arne A Saris Wim H WH Dent Robert R Neely Greg G GG Hager Jörg J

Nature communications 20190201 1

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 = ...[more]

PMID: 30710084

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Project description:BackgroundObesity and its cardiovascular complications are extremely common medical problems, but evidence on how to accomplish weight loss in clinical practice is sparse.MethodsWe conducted a randomized, controlled trial to examine the effects of two behavioral weight-loss interventions in 415 obese patients with at least one cardiovascular risk factor. Participants were recruited from six primary care practices; 63.6% were women, 41.0% were black, and the mean age was 54.0 years. One intervention provided patients with weight-loss support remotely--through the telephone, a study-specific Web site, and e-mail. The other intervention provided in-person support during group and individual sessions, along with the three remote means of support. There was also a control group in which weight loss was self-directed. Outcomes were compared between each intervention group and the control group and between the two intervention groups. For both interventions, primary care providers reinforced participation at routinely scheduled visits. The trial duration was 24 months.ResultsAt baseline, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) for all participants was 36.6, and the mean weight was 103.8 kg. At 24 months, the mean change in weight from baseline was -0.8 kg in the control group, -4.6 kg in the group receiving remote support only (P<0.001 for the comparison with the control group), and -5.1 kg in the group receiving in-person support (P<0.001 for the comparison with the control group). The percentage of participants who lost 5% or more of their initial weight was 18.8% in the control group, 38.2% in the group receiving remote support only, and 41.4% in the group receiving in-person support. The change in weight from baseline did not differ significantly between the two intervention groups.ConclusionsIn two behavioral interventions, one delivered with in-person support and the other delivered remotely, without face-to-face contact between participants and weight-loss coaches, obese patients achieved and sustained clinically significant weight loss over a period of 24 months. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00783315.).

Dataset Information

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

Publications

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

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