3-Hydroxyisobutyrate (3HIB) is a catabolic intermediate of the branched-chain amino acid (BCAA), valine. 3HIB has recently been identified as a bioactive paracrine metabolite that is secreted from muscle and regulates trans-endothelial flux of fatty acids. Increased catabolic flux of BCAA may increase secretion of 3HIB from muscle, leading to increased import of fatty acid into muscle and accumulation of lipotoxic, incompletely esterified intermediates that blunt insulin signalling (2). Accordingly, elevated 3HIB in serum has been observed in individuals with diabetes, and recently to be associated with incident diabetes type 2 (3).
Assessment of cardiovascular risk and risk of diabetes type 2, linked to levels of BCAA.
Patient/subject: No special precaution.
Matrix: Serum or EDTA plasma.
Volume: Minimum volume is 50 µL, but 200 µL is optimal and allows reanalysis.
Preparation and stability: Stable.
Reported values: 15-25 µmol/L
Intraclass correlation coefficient (ICC): na.
1. Midttun, Ø., McCann, A., Aarseth, O., Krokeide, M., Kvalheim, G., Meyer, K., and Ueland, P.M. (2016). Combined measurement of 6 fat-soluble vitamins and 26 water-soluble functional vitamin markers and amino acids in 50 μL of serum or plasma by high-throughput mass spectrometry. Anal Chem 88, 10427-436.
2. Jang, C., Oh, S.F., Wada, S., Rowe, G.C., Liu, L., Chan, M.C., Rhee, J., Hoshino, A., Kim, B., et al. (2016). A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat Med 22, 421-26.
3. Arany, Z., and Neinast, M. (2018). Branched chain amino acids in metabolic disease. Curr Diab Rep 18, 76.