In Vivo Substrate Oxidation in Skeletal Muscle of Mice

Patricia Maria Nunes¹, Alan James Wright¹, Cees Tack², Arend Heerschap¹

A mouse-scale 13C MRS method was developed, to enable the evaluation of knockout mice in vivo for skeletal-muscle substrate oxidation at the level of TCA cycle. [2-13C]acetate or [2,4,6,8-13C]octanoate was infused and yielded sufficient 13C labelling in glutamate C4/C2. Half-maximal 13C enrichments during acetate and octanoate infusion were respectively, 7.21.8min and 30.74.2min for glutamate C4, and for glutamate C2 19.93.9min and 38.311.8min. Relative anaplerotic contribution for TCA-cycle flux were similar in both acetate and octanoate infusions with 0.400.10 and 0.420.20. This study shows the feasibility of 13C MRS to compare in vivo fatty-acid oxidation and TCA-cycle kinetics in mouse skeletal-muscle.