Differential Effects of Beta-Hydroxybutyrate Enantiomers on Induced Pluripotent Stem Derived Cardiac Myocyte Electrophysiology.
Matthew L KlosWanqing HouWenqiang WeiShiwang WengChuyun YanJianping WengEric DevaneyShuxin HanPublished in: Biomolecules (2022)
Beta-hydroxybutyrate (βOHB), along with acetoacetate and acetone, are liver-produced ketone bodies that are increased after fasting or prolonged exercise as an alternative fuel source to glucose. βOHB, as the main circulating ketone body, is not only a G-protein coupled receptor ligand but also a histone deacetylases inhibitor, prompting the reexamination of its role in health and disease. In this study, we compared the effects of two commercial βOHB formulations an enantiomer R βOHB and a racemic mixture ±βOHB on induced pluripotent stem cell cardiac myocytes (iPS-CMs) electrophysiology. Cardiac myocytes were cultured in R βOHB or ±βOHB for at least ten days after lactate selection. Flouvolt or Fluo-4 was used to assay iPS-CMs electrophysiology. We found that while both formulations increased the optical potential amplitude, R βOHB prolonged the action potential duration but ±βOHB shortened the action potential duration. Moreover, ±βOHB increased the peak calcium transient but R βOHB reduced the peak calcium transient. Co-culturing with glucose or fatty acids did not ameliorate the effects, suggesting that βOHB was more than a fuel source. The effect of βOHB on iPS-CMs electrophysiology is most likely stereoselective, and care must be taken to evaluate the role of exogenous βOHB in health and disease.
Keyphrases
- healthcare
- stem cells
- human health
- public health
- left ventricular
- high glucose
- blood glucose
- mental health
- fatty acid
- endothelial cells
- drug induced
- high throughput
- risk assessment
- dna methylation
- high resolution
- physical activity
- palliative care
- heart failure
- gene expression
- high intensity
- metabolic syndrome
- health promotion
- mass spectrometry
- skeletal muscle
- resting state
- single cell
- functional connectivity
- social media
- blood brain barrier