Branched chain amino acids: Passive biomarkers or the key to the pathogenesis of cardiometabolic diseases?

Abstract

The metabolomic approach to research on lifestyle diseases has led to the discovery of new potential biomarkers of pathological conditions as well as key metabolic pathways that may become targets of therapeutic intervention. Current evidence supports plasma branched chain amino acids (BCAAs) as potential diagnostic and prognostic biomarkers of cardiometabolic diseases. However, the biological mechanisms of the associations that have been identified are still not completely understood and should be clarified before implementing BCAA-based biomarkers in the clinical setting. The most crucial issue that needs to be solved first is determining whether BCAA plasma profile disturbances are only passive biomarkers or whether they facilitate dysmetabolic processes. In this context, further research is also warranted to investigate the role of dietary BCAAs. Gaining this knowledge would be significant progress in molecular nutrition research, providing perspective for target therapeutic and prophylactic interventions. This paper provides a comprehensive review of the main hypotheses and mechanistic models that consider circulating BCAAs both as passive biomarkers and as contributors to cardiometabolic diseases.

Transgenerational metabolomic fingerprints in mice ancestrally exposed to the obesogen TBT

“…In parallel, leucine, isoleucine and valine (males, both doses) were discriminant variables decreased in the liver. Current human metabolomics research suggests that BCAAs are valuable diagnostic and prognostic plasma biomarkers of cardiometabolic diseases, including obesity and metabolic syndrome, although the mechanisms underlying the relationship of plasma BCAA to disease processes require further clarification ( Siomkajlo and Daroszewski, 2019 ).…”

Metabolic Syndrome and PCOS: Pathogenesis and the Role of Metabolites

“…On the other hand, some studies have also suggested that BCAAs are associated with insulin resistance, obesity and even T2DM, which have similarities with the phenotypes of PCOS. These results indicate that BCAAs may be involved in the onset of PCOS or serve as biomarkers for PCOS [93,94].…”

Serum metabolomics study of the association between dairy intake and the anti-müllerian hormone annual decline rate

“…Short term changes in dairy intakes by 1.5–2 serving of daily milk intake for one month could not affect plasma BCAAs, proline, and other free amino acids in an intervention study of 102 healthy adults [ 32 ]. Whereas the BCAAs catabolism is tightly regulated, increased dietary intakes of BCAAs have been proposed not to contribute a remarkable elevation in their circulatory levels in prandial state [ 34 , 35 ]. In addition to dietary intake, protein turnover and gene expression of activity of the branched-chain-keto acid dehydrogenase (BCKAD), the rate-limiting enzyme of BCAAs catabolism, also influence their circulatory levels [ 34 , 36 ].…”

“…Whereas the BCAAs catabolism is tightly regulated, increased dietary intakes of BCAAs have been proposed not to contribute a remarkable elevation in their circulatory levels in prandial state [ 34 , 35 ]. In addition to dietary intake, protein turnover and gene expression of activity of the branched-chain-keto acid dehydrogenase (BCKAD), the rate-limiting enzyme of BCAAs catabolism, also influence their circulatory levels [ 34 , 36 ]. Although the cause and effect relationship between insulin resistance and elevated BCAA is unknown, it is believed that insulin activates BCKD, so insulin resistance leads to the decreased catabolism of the amino-acids [ 35 ].…”