TY - JOUR
T1 - Metabolomic Profile of Low Copy-Number Carriers at the Salivary Alpha-Amylase Gene Suggests a Metabolic Shift Towards Lipid-Based Energy Production
AU - Arredouani, Abdelilah
AU - Stocchero, Matteo
AU - Culeddu, Nicola
AU - El-Sayed Moustafa, Julia
AU - Tichet, Jean
AU - Balkau, Beverley
AU - Brousseau, Thierry
AU - Manca, Marco
AU - Falchi, Mario
AU - D.E.S.I.R. study group
N1 - © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
U2 - 10.2337/db16-0315
DO - 10.2337/db16-0315
M3 - Article
C2 - 27436124
SN - 0012-1797
JO - Diabetes
JF - Diabetes
ER -
