1232Relationship between leucine metabolism and executive function development: the GUSTO cohort

Abstract

Abstract Background Molecular biomarkers for cognitive function have also been widely investigated. However, few investigated early development of executive function (EF) comprehensively, which is a higher-level of cognitive function responsible for coordinating other cognitive ability. Methods We investigated the metabolomic biomarkers for EF in a multi-ethnicity birth cohort in Singapore. Circulating level of 165 metabolites were quantified using a nuclear magnetic resonance (NMR)-based metabolomics platform in 457 and 524 children at age 6 and 8 years. EF was assessed in 495 children (∼7 years) using parent-reported Behavior Rating Inventory of Executive Function, Second Edition. We incorporated genetic data and performed mediation analysis to investigate the role of rs1260326 (GCKR) in the relationship between leucine metabolism and EF. Results Higher circulating level of leucine was consistently associated with poorer EFs (Initiate, Working Memory, Plan/Organize, Task-Monitor, and Organization of Materials) after adjusting for age, sex, maternal ethnicity, maternal educational level, household income at recruitment, and child body-mass index (BMI). Comparing to CT genotype, CC genotype in rs1260326 is potentially associated with poorer EFs. But these associations were not mediated via circulating leucine level or BMI. Higher circulating leucine exerts effect on EFs and part of the effect may be via impact on BMI. Leucine-BMI interaction may exist in CT subgroup. Conclusions Our analysis suggested that leucine exerts harmful effect on EF, but at a lower level, leucine-BMI interaction may counteract with the effect of leucine. Key messages Higher level of circulating leucine was associated with poorer EF. Leucine-BMI interaction influences the leucine-EF association.