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Abstract #0297

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

Sung-Han Lin1, Mai T. Huynh1, Zohreh Erfani1, Sasanka Nadishan Gunarathn Wathukara Dewage1, Blanka Kucejova2, Thomas Jue3, Zoltan Kovacs1, Shawn Burgess2, and Jae Mo Park1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, 2UT Southwestern Medical Center, Dallas, TX, United States, 3Biochemistry and Molecular Medicine, UC Davis School of Medicine, Davis, CA, United States

Synopsis

Keywords: Muscle, Hyperpolarized MR (Non-Gas)

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.

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Keywords