Intraperitoneal Injection Of Cardiolipin Boosts Respiratory Function In Skeletal Muscle

: Cardiolipin is a phospholipid found in the inner mitochondrial membrane and, consequently, is involvedin energy metabolism. Research has demonstrated that cardiolipin is released from necrotic cellsfollowing myocardial ischemia and reperfusion injury. Despite its various effects on liver, smooth andcardiac muscle, the impact of increased cardiolipin on skeletal muscle remains unknown. PURPOSE: Toexamine the effects of long-term administration of cardiolipin on aerobic capacity and mitochondrialrespiration of skeletal muscle in a mouse model. METHODS: C57BL/6 mice were randomized to anexperimental and a control group (n = 8/group). The mice were injected 2x/week for 6 weeks with 0.1mlof cardiolipin (1.8 mg/kg body weight) or placebo solution. Concurrently, voluntary running distance wasalso measured using in-cage running wheels. At baseline, week 3 and week 6, aerobic capacity wasassessed by recording time to exhaustion on a treadmill at a speed of 16 m/min. At the experimentalendpoint, the mice were euthanized and the vastus lateralis muscle was extracted and mitochondrialrespiratory capacity was measured by high-resolution respirometry [2 mM malate, 10 mM glutamate,6 mM pyruvate, 5 mM ADP, 10 μM cytochrome C, 10 mM succinate, 2 μg/ml oligomycin, 0.25 μM FCCP].Respiratory control ratio (RCR) and acceptor control ratio (ACR) were calculated. Two-tailed t-tests wereused to compare data between the two groups. RESULTS: Mice injected with cardiolipin showed strongtrends of increased respiration rates. Succinate increased notably (59.83 ± 5.16 vs. 46.03 ± 5.66 pmol/s/mg, p > 0.05) but did not show significance, whereas glutamate (6.76 ± 1.05 vs. 4.12 ± 0.58 pmol/s/mg, p < 0.05) and oligomycin (34.45 ± 2.80 vs. 27.70 ± 2.10 pmol/s/mg, p < 0.05) did. No significantdifferences in voluntary running distance, functional aerobic capacity, RCR or ACR were seen. CONCLUSION: Cardiolipin enhances LEAK respiration and may have a positive effect on oxidativephosphorylation in skeletal muscle. Future experiments include increasing sample size and analyzingmitochondrial density of this tissue.