Metabolomic Profile of Low–Copy Number Carriers at the Salivary α-Amylase Gene Suggests a Metabolic Shift Toward Lipid-Based Energy Production

• DOI: 10.2337/db16-0315
• Publication Date: 2016-07-20T01:54:18Z
• Authors: Abdelilah Arredouani; Matteo Stocchero; Nicola Culeddu; Julia El-Sayed Mo...; ; Jean Tichet; Beverley Balkau; Thierry Brousseau; Marco Manca; Mario Falchi
• Keywords: Adult; 2. Zero hunger; 570; Magnetic Resonance Spectroscopy; DNA Copy Number Variations; ALPHA-AMYLASE; Diabetes; Fatty Acids; 610; Hydroxybutyrates; Lipid Metabolism; NMR; OPLS-DA; Mass Spectrometry; LC-MS; Glucose; Salivary alpha-Amylases; Multivariate Analysis; Carbohydrate Metabolism; Humans; Metabolomics; Dicarboxylic Acids; Female; GC-MS

Low serum salivary amylase levels have been associated with a range of metabolic abnormalities, including obesity and insulin resistance. We recently suggested that low copy number at the AMY1 gene, lower enzyme levels, also increases susceptibility to obesity. To advance our understanding effect variation on metabolism, we compared metabolomic signatures high- low-copy carriers. analyzed, using mass spectrometry nuclear magnetic resonance (NMR), sera healthy normal-weight women carrying either low-AMY1 copies (LAs: four or fewer copies; n = 50) high-AMY1 (HAs: eight more 50). Best-fitting multivariate models (empirical P < 1 × 10-3) NMR data were concordant in showing differences lipid metabolism between two groups. In particular, LA carriers showed long- medium-chain fatty acids, higher dicarboxylic acids 2-hydroxybutyrate (a known marker glucose malabsorption). Taken together, these observations suggest increased reliance through β- ω-oxidation reduced cellular uptake consequent diversion acetyl-CoA into ketogenesis. Our are line previously reported delayed after starch consumption. Further functional studies needed extrapolate from findings implications for biochemical pathways.