Amino Acid Metaboli is Altered in Adolescents with Nonalcoholic Fatty Liver Disease—An Untargeted, High Resolution Metabolomics Study
Ran Jin,Sophia Banton,ViLinh T. Tran,Juna V. Konomi
DOI:
http://dx.doi.org/10.1016/j.jpeds.2016.01.026 Abstract
Objective
To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents.
Study design
This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30had hepatic steatosis ≥5% and 9 were matched controls with hepatic steatosis <5%. Fasting plaa samples were yzed in triplicate using ultra-high resolution metabolomics on a Thermo Fisher Q Exactive mass spectrometry system, coupled with C18 reverse phase liquid chromatography. Differences in plaa metabolites between adolescents with and without nonalcoholic fatty liver disease (NAFLD) were determined by independentttests and visualized using Manhattan plots. Untargeted pathway yses using Mummichog were performed among the significant metabolites to identify pathways that were most dysregulated in NAFLD.
Results
The metabolomics ysis yielded 9583 metabolites, and 7711 with 80% presence across all samples remained for statistical testing. Of these, 478 metabolites were associated with the presence of NAFLD compared with the matched controls. Pathway ysis revealed that along with lipid metaboli, several major amino acid pathways were dysregulated in NAFLD, with tyrosine metaboli being the most affected.
Conclusions
Metabolic pathways of several amino acids are significantly disturbed in adolescents with elevated hepatic steatosis. This is a novel finding and suggests that these pathways may be integral in the mechanis of NAFLD.
