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

作者：Perry, Rachel J.; Peng, Liang; Cline, Gary W.; Petersen, Kitt Falk; Shulman, Gerald I.^*

来源：Cell Metabolism, 2017, 25(3): 749-756.

DOI：10.1016/j.cmet.2016.12.017

• PITUITARY-ADRENAL AXIS
• GLUCONEOGENESIS
• RAT
• KETOGENESIS
• SUPPRESSION
• COENZYME
• KETOSIS
• LIVER

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 noninvasively 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-13(4)] b-hydroxybutyrate (b-OHB). Here, we show a strong correlation (R-2 = 0.86, p < 0.0001) between hepatic acetyl-CoA content and b-OHB turnover in rats with varying degrees of fasting hyperglycemia and insulin resistance. These studies demonstrate that b-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.

• 出版日期2017-3-7
• 单位中日友好医院