15)BMC Med.2017 Feb 23;15(1):37.

Relationship between salivary/pancreatic amylase and body mass index: a systems biology approach

Amélie Bonnefond 1Loïc Yengo 2 3Aurélie Dechaume 2Mickaël Canouil 2Maxime Castelain 2Estelle Roger 2Frédéric Allegaert 2Robert Caiazzo 4 5Violeta Raverdy 4 5Marie Pigeyre 4 5Abdelilah Arredouani 6Jean-Michel Borys 7Claire Lévy-Marchal 8Jacques Weill 9Ronan Roussel 10 11 12Beverley Balkau 13Michel Marre 10 11 12François Pattou 4 5Thierry Brousseau 14Philippe Froguel 15 16

Abstract

Background: Salivary (AMY1) and pancreatic (AMY2) amylases hydrolyze starch. Copy number of AMY1A (encoding AMY1) was reported to be higher in populations with a high-starch diet and reduced in obese people. These results based on quantitative PCR have been challenged recently. We aimed to re-assess the relationship between amylase and adiposity using a systems biology approach.

Methods: We assessed the association between plasma enzymatic activity of AMY1 or AMY2, and several metabolic traits in almost 4000 French individuals from D.E.S.I.R. longitudinal study. The effect of the number of copies of AMY1A (encoding AMY1) or AMY2A (encoding AMY2) measured through droplet digital PCR was then analyzed on the same parameters in the same study. A Mendelian randomization analysis was also performed. We subsequently assessed the association between AMY1A copy number and obesity risk in two case-control studies (5000 samples in total). Finally, we assessed the association between body mass index (BMI)-related plasma metabolites and AMY1 or AMY2 activity.

Results: We evidenced strong associations between AMY1 or AMY2 activity and lower BMI. However, we found a modest contribution of AMY1A copy number to lower BMI. Mendelian randomization identified a causal negative effect of BMI on AMY1 and AMY2 activities. Yet, we also found a significant negative contribution of AMY1 activity at baseline to the change in BMI during the 9-year follow-up, and a significant contribution of AMY1A copy number to lower obesity risk in children, suggesting a bidirectional relationship between AMY1 activity and adiposity. Metabonomics identified a BMI-independent association between AMY1 activity and lactate, a product of complex carbohydrate fermentation.

Conclusions: These findings provide new insights into the involvement of amylase in adiposity and starch metabolism.