Determinants of plasma branched-chain amino acids and associations with cardiometabolic biomarkers and proteomic signatures
Metabolism and Target Organ Damage, 2026
Luo X., He X., Wang Y., He Q., Zhao Y., Wang T., Dong Y., Jiao A., Li R., Li Y., Li F., Li S., Zhang S., Xue Q., Wen Y., Yang Y., Pan X.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Metabolic Diseases CVD Nutritional Science | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
Aim: We aimed to identify dietary and non-dietary determinants of plasma branched-chain amino acids (BCAAs), evaluate their associations with comprehensive biomarkers of cardiometabolic health (CMH), and characterize BCAA-related proteomic signatures to clarify potential biological pathways underlying these associations.
Methods: This observational study utilized baseline data from the UK Biobank. Multivariable linear regression models were applied to evaluate associations of dietary and non-dietary factors with plasma BCAAs among 28,273 participants. Subsequent models assessed relationships between these amino acids and comprehensive cardiometabolic biomarkers in 22,779 participants. Using high-throughput proteomics in a subcohort of 2,351 individuals, proteins associated with BCAAs were identified, followed by pathway enrichment and protein-protein interaction analyses.
Results: Plasma BCAAs were positively associated with animal-based foods and total animal protein intake, but inversely associated with plant-based dietary components. Adiposity exhibited strong positive associations, whereas older age, female sex, and higher physical activity correlated with lower BCAAs. Elevated BCAAs were consistently associated with adverse glycemic and lipid profiles alongside impaired renal function, with the strongest association observed for triglycerides. Proteomic analyses identified 172 consensus proteins converging on core metabolic pathways, with LEP as a central hub. Beyond these shared signatures, individual BCAA species exhibited distinct functional networks: leucine-specific proteins (centered on CXCL8 and SDC1) were primarily associated with chemotaxis and cell migration, whereas valine-specific proteins (centered on F10 and PLAT) were associated with coagulation and fibrinolysis.
Conclusion: Circulating BCAAs are significantly influenced by modifiable host factors, particularly dietary components. They are associated with cardiometabolic risk through distinct proteomic signaling cascades.