3-Hydroxyisobutyrate (3-HIB) is an intermediate in the metabolism of the branched-chain amino acid valine that is secreted by skeletal muscle. [1] [2] It dose-dependently increases fatty acid uptake by human umbilical vein endothelial cells (HUVECs) when used at concentrations ranging from 0.1 to 100 mM. [3] 3-HIB also increases fatty acid uptake and lipid accumulation in mouse skeletal muscle when administered in drinking water. The levels of 3-HIB in muscle are increased in db/db diabetic mice and in humans with diabetes. Human plasma levels are increased in obesity and correlate with a future risk of type 2 diabetes.[3] In addition, human serum levels of 3-HIB decrease by 2.5-fold immediately following an exercise regimen of 2.5 hours of running for three days. [1]
Reference:
[1]. Nieman, D.C., Shanely, R.A., Gillitt, N.D., et al. Serum metabolic signatures induced by a three-day intensified exercise period persist after 14 h of recovery in runners. J. Proteome Res. 12(10), 4577-4584 (2013).
[2]. Jang, C., Oh, S.F., Wada, S., et al. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat. Med. 22(4), 421-426 (2016).
[3]. Mardinoglu, A., Gogg, S., Lotta, L., et al. Elevated plasma levels of 3-hydroxyisobutyric acid are associated with incident type 2 diabetes. EBioMedicine 27, 151-155 (2018).