Abdelilah Arredouani
Qatar Foundation, Qatar
Title: Metabolomic profile of low copy-number carriers at the salivary alpha-amylase gene suggests a Metabolic shift towards lipid-based energy production
Biography
Biography: Abdelilah Arredouani
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.