Abdurrachim, D., Woo, C.C., Teo, X.Q. et al. A new hyperpolarized 13C ketone body probe reveals an increase in acetoacetate utilization in the diabetic rat heart. Sci Rep 9, 5532 (2019). https://doi.org/10.1038/s41598-019-39378-w
Abstract:
Emerging studies have recently shown the potential importance of ketone bodies in cardio-metabolic health. However, techniques to determine myocardial ketone body utilization in vivo are lacking. In this work, we developed a novel method to assess myocardial ketone body utilization in vivo using hyperpolarized [3-13C]acetoacetate and investigated the alterations in myocardial ketone body metabolism in diabetic rats. Within a minute upon injection of [3-13C]acetoacetate, the production of [5-13C]glutamate and [1-13C] acetylcarnitine can be observed real time in vivo. In diabetic rats, the production of [5-13C]glutamate was elevated compared to controls, while [1-13C]acetylcarnitine was not different. This suggests an increase in ketone body utilization in the diabetic heart, with the produced acetyl-CoA channelled into the tricarboxylic acid cycle. This observation was corroborated by an increase activity of succinyl-CoA:3-ketoacid-CoA transferase (SCOT) activity, the rate-limiting enzyme of ketone body utilization, in the diabetic heart. The increased ketone body oxidation in the diabetic hearts correlated with cardiac hypertrophy and dysfunction, suggesting a potential coupling between ketone body metabolism and cardiac function. Hyperpolarized [3-13C]acetoacetate is a new probe with potential for non-invasive and real time monitoring of myocardial ketone body oxidation in vivo, which offers a powerful tool to follow disease progression or therapeutic interventions.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This study was supported by an intramural funding (Asian neTwork for Translational Research and Cardiovascular Trials, ATTRaCT) from A*STAR Biomedical Research Council.