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

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

Author information

1
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
2
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
3
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: gerald.shulman@yale.edu.

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 [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

PMID:
28111213
PMCID:
PMC5342911
DOI:
10.1016/j.cmet.2016.12.017
[Indexed for MEDLINE]
Free PMC Article

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