Assessment of differential activation of TCA cycle activity and PDH flux by DCA in skeletal muscle using hyperpolarized [2-13C,3-2H3]pyruvate

Motivation: The linkage of PDH flux and the TCA remains unexplored in skeletal muscle. Goal(s): To compare drug-modulated PDH activation and the TCA cycle activity in skeletal muscle. Approach: 13C-labeled products, including acetyl-L-carnitine and glutamate, from hyperpolarized [2-13C,3-2H3]pyruvate was quantified from rat skeletal muscle at baseline and after dichloroacetate treatment. Results: The dichloroacetate-induced PDH activation was detected with the smaller activation of glutamate, suggesting that the TCA cycle activity was not proportional to the PDH flux in the skeletal muscle. Impact: The dichloroacetate-induced PDH activation was detected with a smaller activation of glutamate, suggesting that the TCA cycle activity was not proportional to the PDH flux in the skeletal muscle. This highlights that ALCAR may play a significant role.