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

Publication date: Available online 19 January 2017
Source:Cell Metabolism
Author(s): Rachel J. Perry, Liang Peng, Gary W. Cline, Kitt Falk Petersen, Gerald I. Shulman
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.

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Teaser

Levels of acetyl-CoA, a key metabolite in metabolism and signaling, are technically challenging to measure. Perry et al. present a novel method to non-invasively assess hepatic acetyl-CoA content in vivo by assessing rates of β-OHB turnover, validating this approach in rats with varying degrees of fasting hyperglycemia and insulin resistance.


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