Intraperitoneal Administration of Cardiolipin Enhances Mitochondrial Respiration in Skeletal Muscle of Male Mice

Cardiolipin is a phospholipid located in the inner mitochondrial membrane and is released following myocardial ischemia-reperfusion injury. While cardiolipin has documented effects in several tissues, its impact on skeletal muscle function and mitochondrial respiration remains unclear. The purpose of this study was to investigate the effects of exogenously elevated cardiolipin on aerobic capacity and mitochondrial respiratory function in skeletal muscle using a mouse model.

Male C57BL/6 mice were randomized into an experimental group (n = 11) receiving cardiolipin injections and a control group (n = 12) receiving a placebo solution. Mice were injected twice weekly for 6 weeks with 0.1 mL of cardiolipin (0.5 mg/mL) or placebo. Voluntary running distance was monitored throughout the intervention. Aerobic capacity was assessed at baseline, week 3, and week 6 by measuring time to exhaustion during treadmill running at a constant speed of 16 m min^-1. Following the intervention, mice were euthanized, the vastus lateralis muscle was excised, and mitochondrial respiratory capacity was evaluated using high-resolution respirometry. Mitochondrial density was assessed by immunoblotting.

Mice receiving cardiolipin exhibited increased skeletal muscle oxygen consumption compared with controls. No differences in mitochondrial density were observed between groups, suggesting that the enhanced oxygen consumption was not associated with increased mitochondrial content but may instead reflect alterations in mitochondrial respiratory efficiency.

Exogenously elevated cardiolipin is associated with enhanced skeletal muscle mitochondrial respiratory function without altering mitochondrial density, which may indicate improved mitochondrial efficiency. These findings provide novel insight into the potential role of cardiolipin in skeletal muscle energy metabolism and aerobic performance. Future studies should explore the combined effects of cardiolipin administration and exercise training on skeletal muscle respiratory capacity and further investigate the underlying mechanisms.