Muscle hypertrophy induced by myostatin inhibition is suppressed by rapamycin administration

Abstract Text: Recent studies have shown that myostatin (MSTN), a skeletal muscle specific negative growth factor, may regulate skeletal muscle mass through the mTOR pathway. The mTOR pathway is known to be blocked by rapamycin (RAP), thus it was hypothesized that muscle hypertrophy induced by MSTN inhibition would be blocked by RAP treatment. This study was designed to examine the effect of RAP administration on muscle growth in MSTN-propeptide transgenic mice, a hypermuscular phenotype by MSTN inhibition. 5 week old male heterozygous MSTN-propeptide transgenic mice and wild type littermates were administered with 0 or 3 mg/kg body weight of RAP intraperitoneally every other day for 4 weeks. At the end of RAP treatment, animals were sacrificed, and gastrocnemius, plantaris, and soleus muscles were dissected, weighed, and snap-frozen for later analysis. Body weight gain of transgenic mice was greater (P<0.01) than that of wild type mice. RAP suppressed (P<0.05) body weight gain about 40% in both genotypes. Soleus, plantaris, and gastrocnemius muscle weights of transgenic mice were greater (P<0.05) than those of wild type mice. RAP suppressed (P<0.05) muscle growth in both genotypes, but the extent of suppression was greater in transgenic mice than in wild type mice (6.6% vs 18.6% in plantaris, and 20.7% vs 24.8% in gastrocnemius). When the expressions of MyoD and myogenin were analyzed by real time PCR, expressions of these myogenic regulatory factors were not affected by either genotype or RAP administration. The current result of suppressing muscle growth by RAP in MSTN-propeptide transgenic mice supports that the mTOR pathway is involved in the regulation of muscle growth by MSTN. 

Keywords: myostatin, rapamycin, mTOR pathway