Abstract
Myostatin (Mstn) inactivation or inhibition is considered as a promising treatment for various muscle-wasting disorders because it promotes muscle growth. However, myostatin-deficient hypertrophicmuscles show strong fatigability associated with abnormal mitochondria and lipid metabolism. Here, weinvestigated whether endurance training could improve lipid metabolism and mitochondrial membranelipid composition in mice where theMstngene was genetically ablated (Mstn /-mice). InMstn /-mice, 4weeks of daily running exercise sessions (65e70% of the maximal aerobic speed for 1 h) improvedsignificantly aerobic performance, particularly the endurance capacity (up toþ280% compared withuntrainedMstn /-mice), to levels comparable to those of trained wild type (WT) littermates. Theexpression of oxidative and lipid metabolism markers also was increased, as indicated by the upregu-lation of theCpt1,Ppar-dandFasngenes. Moreover, endurance training also increased, but far less thanWT, citrate synthase level and mitochondrial protein content. Interestingly endurance trainingnormalized the cardiolipin fraction in the mitochondrial membrane ofMstn /-muscle compared withWT. These results suggest that the combination of myostatin inhibition and endurance training couldincrease the muscle mass while preserving the physical performance with specific effects on cardiolipinand lipid-related pathways.