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

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Abdelilah Arredouani, Matteo Stocchero, Nicola Culeddu, Julia El-Sayed Moustafa, Jean Tichet, Beverley Balkau, Thierry Brousseau, Marco Manca, Mario Falchi, D.E.S.I.R. study group

Original languageEnglish
JournalDiabetes
Early online date19 Jul 2016
DOIs
Publication statusPublished - 1 Aug 2016

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Abstract

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, 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 analysed, using mass spectrometry and NMR, the sera of healthy normal-weight women carrying either low (LA:≤4 copies; n=50) or high (HA:≥8 copies; n=50) AMY1 copies. Best fitting multivariate models (empirical P<1x10(-3)) of MS 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 (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.

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