Serum metabolome alterations in hyperhomocysteinemia based on targeted and non-targeted MS-platforms

Abstract

Background and aims

Hyperhomocysteinemia (Hhcy) is a pathological condition marked by increased level of homocysteine and serves as an independent risk factor for a range of diseases including cardiovascular diseases and Alzheimer’s disease. This study aims to examine alterations in Hhcy-related metabolites using serum metabolomics and unravel the distinct metabolic pathways involved, thereby offering a theoretical foundation for the early prevention and treatment of Hhcy.

Methods

Serum samples were collected from 56 individuals with Hhcy and 44 healthy controls. Metabolic alterations in Hhcy were assessed through multi-platform serum metabolomics analyses. Through multivariate statistical analysis and regression modeling, distinct metabolites in the serum were identified, and various metabolic pathways associated with Hhcy were investigated.

Results

Our findings revealed 21 significant different metabolites that distinguished Hhcy from healthy controls. These varied metabolites primarily comprised 10 organic acids, 4 amino acids, 2 fatty acids, and 5 other metabolites. The key differential metabolic pathways identified were the TCA cycle, pyruvate metabolism, arginine biosynthesis, as well as alanine, aspartate, and glutamate metabolism.

Conclusions

This study elucidated the variances in metabolic profiles between Hhcy and healthy control groups, highlighting distinct metabolic pathways that may help explain the etiology of Hhcy. These findings offer valuable insights to address the knowledge gaps related to the metabolic alterations associated with Hhcy.