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Network Analysis of Metabolite GWAS Hits: Implication of CPS1 and the Urea Cycle in Weight Maintenance
- Source :
- PLOS ONE, 11(3):e0150495. Public Library of Science, PLoS ONE, Matone, A, Scott-Boyer, M-P, Carayol, J, Fazelzadeh, P, Lefebvre, G C, Valsesia, A, Charon, C, Vervoort, J, Astrup, A, Saris, W H M, Morine, M & Hager, J 2016, ' Network analysis of metabolite GWAS hits : Implication of CPS1 and the urea cycle in weight maintenance ', P L o S One, vol. 11, no. 3, e0150495 . https://doi.org/10.1371/journal.pone.0150495, PLoS ONE, 11(3), PLoS ONE 11 (2016) 3, PLoS ONE, Vol 11, Iss 3, p e0150495 (2016)
- 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-11 and rs12613336, p-value = 1.368e-08). Furthermore, gene expression in the adipose tissue showed that CPS1 expression levels were associated with successful weight maintenance 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 analyzed, 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.
- Subjects :
- 0301 basic medicine
Proteomics
Male
Physiology
lcsh:Medicine
Gene Expression
Genetic Networks
Biochemistry
Voeding, Metabolisme en Genomica
chemistry.chemical_compound
Weight loss
Carbamoyl phosphate
Medicine and Health Sciences
Metabolites
Urea
Gene Regulatory Networks
Amino Acids
lcsh:Science
Multidisciplinary
Organic Compounds
Chromosome Mapping
Genomics
Metabolism and Genomics
Mitochondria
Carbamoyl-Phosphate Synthase (Ammonia)
Chemistry
Physiological Parameters
Osmolyte
Metabolisme en Genomica
Urea cycle
Physical Sciences
Metabolome
Nutrition, Metabolism and Genomics
Protein Interaction Networks
Female
medicine.symptom
Network Analysis
Research Article
Adult
Computer and Information Sciences
Carbamyl Phosphate
Quantitative Trait Loci
Glycine
Biochemie
Biology
Polymorphism, Single Nucleotide
03 medical and health sciences
Voeding
Ammonia
Weight Loss
medicine
Genetics
Genome-Wide Association Studies
Life Science
Humans
Obesity
Nutrition
VLAG
Caloric Restriction
lcsh:R
Organic Chemistry
Body Weight
Chemical Compounds
Biology and Life Sciences
Proteins
Computational Biology
Lipid metabolism
Human Genetics
Genome Analysis
Lipid Metabolism
Betaine
030104 developmental biology
Metabolism
chemistry
Aliphatic Amino Acids
lcsh:Q
Insulin Resistance
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PLOS ONE, 11(3):e0150495. Public Library of Science, PLoS ONE, Matone, A, Scott-Boyer, M-P, Carayol, J, Fazelzadeh, P, Lefebvre, G C, Valsesia, A, Charon, C, Vervoort, J, Astrup, A, Saris, W H M, Morine, M & Hager, J 2016, ' Network analysis of metabolite GWAS hits : Implication of CPS1 and the urea cycle in weight maintenance ', P L o S One, vol. 11, no. 3, e0150495 . https://doi.org/10.1371/journal.pone.0150495, PLoS ONE, 11(3), PLoS ONE 11 (2016) 3, PLoS ONE, Vol 11, Iss 3, p e0150495 (2016)
- Accession number :
- edsair.doi.dedup.....1f01d04bb1261399ed4d029030e64d42