Metabolomic profile of low-copy number carriers at the salivary α-amylase gene suggests a metabolic shift toward lipid-based energy production

Abdelilah Arredouani, Matteo Stocchero, Nicola Culeddu, Julia El Sayed Moustafa, Jean Tichet, Beverley Balkau, Thierry Brousseau, Marco Manca, Mario Falchi

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 3 1023) 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 band v-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.

Original languageEnglish
Pages (from-to)3362-3368
Number of pages7
JournalDiabetes
Volume65
Issue number11
DOIs
Publication statusPublished - 1 Nov 2016

    Fingerprint

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Arredouani, A., Stocchero, M., Culeddu, N., Moustafa, J. E. S., Tichet, J., Balkau, B., Brousseau, T., Manca, M., & Falchi, M. (2016). Metabolomic profile of low-copy number carriers at the salivary α-amylase gene suggests a metabolic shift toward lipid-based energy production. Diabetes, 65(11), 3362-3368. https://doi.org/10.2337/db16-0315