title: Metabolomic Profile of Low-Copy Number Carriers at the Salivary α-Amylase Gene Suggests a Metabolic Shift Toward Lipid-Based Energy Production.
abstract: Low serum salivary amylase levels have been associated with a range of metabolic abnormalities, including obesity and insulin resistance. We recently suggested that a low copy number at the AMY1 gene, associated with lower enzyme levels, also increases susceptibility to obesity. To advance our understanding of the effect of AMY1 copy number variation on metabolism, we compared the metabolomic signatures of high- and low-copy number carriers. We analyzed, using mass spectrometry and nuclear magnetic resonance (NMR), the sera of healthy normal-weight women carrying either low-AMY1 copies (LAs: four or fewer copies; n = 50) or high-AMY1 copies (HAs: eight or more copies; n = 50). Best-fitting multivariate models (empirical P < 1 × 10-3) of mass spectrometry and NMR data were concordant in showing differences in lipid metabolism between the two groups. In particular, LA carriers showed lower levels of long- and medium-chain fatty acids, and higher levels of dicarboxylic fatty acids and 2-hydroxybutyrate (a known marker of glucose malabsorption). Taken together, these observations suggest increased metabolic reliance on fatty acids in LA carriers through β- and ω-oxidation and reduced cellular glucose uptake with consequent diversion of acetyl-CoA into ketogenesis. Our observations are in line with previously reported delayed glucose uptake in LA carriers after starch consumption. Further functional studies are needed to extrapolate from our findings to implications for biochemical pathways.
authors.affiliation: Hamad Ben Khalifa University, Qatar Biomedical Research Institute, Diabetes Research Centre, Qatar Foundation, Doha, Qatar aarredouani@qf.org.qa mario.falchi@kcl.ac.uk.|Department of Genomics of Common Disease, Imperial College London, U.K.
authors.forename: Abdelilah
authors.identifier: http://orcid.org/0000-0002-5060-916X
authors.initials: A
authors.lastname: Arredouani
authors.affiliation: S-IN Soluzioni Informatiche, Vicenza, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Stocchero
authors.affiliation: Istituto di Chimica Biomolecolare, Laboratory of Nuclear Magnetic Resonance, Consiglio Nazionale delle Ricerche, Sassari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Culeddu
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, St. Thomas' Hospital Campus, London, U.K.
authors.forename: Julia El-Sayed
authors.initials: JE
authors.lastname: Moustafa
authors.affiliation: Institut Inter-Régional Pour la Santé, La Riche, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Tichet
authors.affiliation: Centre de Recherche en Epidémiologie et Santé des Populations, Le Centre de Recherche en Epidémiologie et Santé des Populations, INSERM U1018, Renal and Cardiovascular Epidemiology, Villejuif, France.|Universities Versailles-St. Quentin and Paris-Sud, UMRS 1018, Villejuif, France.
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.affiliation: UF8832, Biochimie Automatisée, Pôle de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire, Lille, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Brousseau
authors.affiliation: Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, the Netherlands.|Accelerators & Technology Sector, CERN, Geneva, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Manca
authors.affiliation: Department of Genomics of Common Disease, Imperial College London, U.K. aarredouani@qf.org.qa mario.falchi@kcl.ac.uk.|Department of Twin Research & Genetic Epidemiology, King's College London, St. Thomas' Hospital Campus, London, U.K.
authors.forename: Mario
authors.initials: M
authors.lastname: Falchi
mesh_terms: D000328:Adult; D050260:Carbohydrate Metabolism / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D003998:Dicarboxylic Acids / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006885:Hydroxybutyrates / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D055291:Salivary alpha-Amylases / Q000235:genetics*
chemical_list: D003998:Dicarboxylic Acids; D005227:Fatty Acids; D006885:Hydroxybutyrates; D055291:Salivary alpha-Amylases; D005947:Glucose; C031570:2-hydroxybutyric acid