A Non-invasive Method to Assess Hepatic Acetyl-CoA In Vivo

Cell Metab. 2017 Mar 7;25(3):749-756. doi: 10.1016/j.cmet.2016.12.017. Epub 2017 Jan 19.


Acetyl-coenzyme A (acetyl-CoA) is a critical metabolic signaling molecule that regulates gluconeogenesis, pyruvate oxidation, protein acetylation, and steroid and fatty acid biosynthesis; however, measurements of this metabolite using standard biochemical approaches are technically demanding, and there is currently no method to non-invasively assess hepatic acetyl-CoA content in vivo. To this end, we developed and validated a method to non-invasively detect differences in hepatic acetyl-CoA content in vivo across a 5-fold range of physiological acetyl-CoA concentrations by assessing the turnover of [13C4]β-hydroxybutyrate (β-OHB). Here, we show a strong correlation (R2 = 0.86, p < 0.0001) between hepatic acetyl-CoA content and β-OHB turnover in rats with varying degrees of fasting hyperglycemia and insulin resistance. These studies demonstrate that β-OHB turnover can be used as a surrogate to non-invasively assess hepatic acetyl-CoA content, thereby allowing researchers to further elucidate the role of this metabolite in the regulation of hepatic gluconeogenesis and other metabolic processes in vivo.

Keywords: acetyl-CoA; ketone turnover; β-hydroxybutyrate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • 3-Hydroxybutyric Acid / metabolism
  • Acetyl Coenzyme A / metabolism*
  • Animals
  • Blood Glucose / metabolism
  • Fasting / blood
  • Feeding Behavior / drug effects
  • Glucose / pharmacology
  • Glycerol / pharmacology
  • Hyperglycemia / blood
  • Hyperglycemia / metabolism
  • Insulin / pharmacology
  • Liver / metabolism*
  • Male
  • Metabolic Networks and Pathways / drug effects
  • Models, Biological
  • Rats
  • Starvation / metabolism


  • Blood Glucose
  • Insulin
  • Acetyl Coenzyme A
  • Glucose
  • Glycerol
  • 3-Hydroxybutyric Acid