Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 499642
Title Network analysis of metabolite GWAS hits : Implication of CPS1 and the urea cycle in weight maintenance
Author(s) Matone, Alice; Scott-Boyer, Marie Pier; Carayol, Jerome; Fazelzadeh, Parastoo; Lefebvre, Gregory; Valsesia, Armand; Charon, Celine; Vervoort, Jacques; Astrup, Arne; Saris, Wim H.M.; Morine, Melissa; Hager, Jörg
Source PLoS One 11 (2016)3. - ISSN 1932-6203
DOI https://doi.org/10.1371/journal.pone.0150495
Department(s) Chair Nutrition Metabolism and Genomics
Biochemistry
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2016
Abstract

Background and Scope Weight loss success is dependent on the ability to refrain from regaining the lost weight in time. This feature was shown to be largely variable among individuals, and these differences, with their underlying molecular processes, are diverse and not completely elucidated. Altered plasma metabolites concentration could partly explain weight loss maintenance mechanisms. In the present work, a systems biology approach has been applied to investigate the potential mechanisms involved in weight loss maintenance within the Diogenes weight-loss intervention study. Methods and Results A genome wide association study identified SNPs associated with plasma glycine levels within the CPS1 (Carbamoyl-Phosphate Synthase 1) gene (rs10206976, p-value = 4.709e- II and rs12613336, p-value = 1.368e-08). Furthermore, gene expression in the adipose tis sue showed that CPS1 expression levels were associated with successful weight mainte nance and with several SNPs within CPS1 (cis-eQTL). In order to contextualize these results, a gene-metabolite interaction network of CPS1 and glycine has been built and ana lyzed, showing functional enrichment in genes involved in lipid metabolism and one carbon pool by folate pathways. Conclusions CPS1 is the rate-limiting enzyme for the urea cycle, catalyzing carbamoyl phosphate from ammonia and bicarbonate in the mitochondria. Glycine and CPS1 are connected through the one-carbon pool by the folate pathway and the urea cycle. Furthermore, glycine could be linked to metabolic health and insulin sensitivity through the betaine osmolyte. These considerations, and the results from the present study, highlight a possible role of CPS1 and related pathways in weight loss maintenance, suggesting that it might be partly genetically determined in humans.

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