(P14-006-24) Mitochondrial Transplants Did Not Improve Exercise Performance, but Altered Exercise-Induced Immune Response in C57Bl6 Mice

Objectives: In the current study we determined if weekly mitochondrial transplants given to animals undergoing a muscle damaging exercise training protocol will improve performance and reduce exercise-induced muscle damage and immune responses.

Methods: Eight-week-old C57/BL6 male mice were allocated to one of two groups; group 1 (n=7) received a weekly mitochondrial transplant and group 2 (n=7) an equal volume of vehicle (PBS) on the same schedule for 6 weeks. Mitochondria were harvested from the livers of C57/BL6 male mice (11-13 weeks of age). Each mouse received mitochondria at a dose of 20ug/g (suspended in PBS for a total volume of 100ul) or a 100ul of PBS (control group) via the retroorbital vein. All mice underwent a muscle damaging training protocol; animals ran 3 times a week for 1-hour on a treadmill with a 15° decline for the 6 weeks study period. A run-to-fatigue (RTF) test was performed at baseline, and again after 4 and 6 weeks of training. Blood was collected immediately after the last RTF test for cytokine (IL-1β, IL-6 and TNF-α) measurements. Tissues were harvested 24 hours after the last RTF test for histological analysis and transcript measurements of PGC1-α and TFAM in the tibialis anterior (TA) muscle and liver.

Results: No significant differences were found in the in the run performance between groups after 4 (p = 0.71) and 6 weeks (p = 0.99). Average run time at week 6 was 102.95 minutes for group 1 and 103.91 minutes for group 2. Histological analysis of the TA did not show differences in damage-associated centralized nuclei and expression of mitochondrial proteins did not differ between groups (PGC1-α, p = 0.71; TFAM, p = 0.99). In the liver no difference was detected for TFAM expression (p = 0.88), however, PGC1-α transcripts were significantly decreased in the mitochondrial transplanted group (p = 0.01). Inflammatory cytokines measured immediately after exercise showed no difference in TNF-α (p = 0.99) and IL-1β (p = 0.78) between groups, but IL-6 levels were significantly decreased in the mitochondrial transplanted group (p = 0.03).

Conclusions: Mitochondrial transplant therapy did not result in changes in run performance. However, changes in inflammatory response to exercise were observed, with a reduction in exercise-induced IL-6.

Funding Sources: University of Memphis, Indirect Cost Recovery Fund (van der Merwe)