Perry Rachel J, Peng Liang, Cline Gary W, Petersen Kitt Falk, Shulman Gerald I
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
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.
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 [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.
乙酰辅酶A（acetyl-CoA）是一种关键的代谢信号分子，可调节糖异生、丙酮酸氧化、蛋白质乙酰化以及类固醇和脂肪酸的生物合成；然而，使用标准生化方法测量这种代谢物在技术上要求很高，目前尚无在体内非侵入性评估肝脏乙酰辅酶A含量的方法。为此，我们开发并验证了一种方法，通过评估[C]β-羟基丁酸酯（β-OHB）的周转率，在体内非侵入性地检测生理乙酰辅酶A浓度5倍范围内肝脏乙酰辅酶A含量的差异。在此，我们展示了在不同程度的空腹高血糖和胰岛素抵抗大鼠中，肝脏乙酰辅酶A含量与β-OHB周转率之间存在强相关性（R = 0.86，p < 0.0001）。这些研究表明，β-OHB周转率可作为一种替代指标，用于非侵入性评估肝脏乙酰辅酶A含量，从而使研究人员能够进一步阐明这种代谢物在体内肝脏糖异生和其他代谢过程调节中的作用。
