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

Citation
Perry, R. J., et al. “A Non-Invasive Method To Assess Hepatic Acetyl-Coa In Vivo.”. Cell Metabolism, pp. 749-756.
Center Yale University
Author Rachel J Perry, Liang Peng, Gary W Cline, Kitt Falk Petersen, Gerald I Shulman
Keywords acetyl-CoA, ketone turnover, β-hydroxybutyrate
Abstract

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 [C]β-hydroxybutyrate (β-OHB). Here, we show a strong correlation (R = 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.

Year of Publication
2017
Journal
Cell metabolism
Volume
25
Issue
3
Number of Pages
749-756
Date Published
12/2017
ISSN Number
1932-7420
DOI
10.1016/j.cmet.2016.12.017
Alternate Journal
Cell Metab.
PMID
28111213
PMCID
PMC5342911
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