Undernutrition regulates the expression of a novel splice variant of myostatin and insulin-like growth factor 1 in ovine skeletal muscle

• We have recently identified a myostatin splice variant (MSV) that binds to and antagonizes the canonical signaling of myostatin.
• This is the first study showing that short-term underfeeding, which results in the reduction of the mass of skeletal muscles, is associated with a decrease in the concentration of MSV mRNA, while the abundance of MSV protein was moderately increased.
• In contrast, the abundance of myostatin protein did not change with undernutrition. Therefore, the modest increase in the abundance of MSV, which could potentially decrease the bioavailability of myostatin, was insufficient to overcome the effect of undernutrition in this study.
• We observed the expected reduction in expression of IGF-1 mRNA in skeletal muscles that were undergoing atrophy due to undernutrition.
• Our study suggests that the myostatin/MSV axis may be less important than that of IGF1 in regulating the wasting, or prevention of wasting, respectively, of skeletal muscles during undernutrition.

Undernutrition suppresses the growth of skeletal muscles and alters the expression of insulin-like growth factor 1 (IGF1), a key mitogen, and myostatin, a potent inhibitor of myogenesis. These changes can explain, at least in part, the reduced growth of skeletal muscles in underfed lambs. We have recently identified a myostatin splice variant (MSV) that binds to and antagonizes the canonical signaling of myostatin. In the present study, we hypothesized that the expression of MSV would be reduced in conjunction with myostatin and IGF1 in response to underfeeding in skeletal muscles of sheep. Young growing ewes were fed either ad libitum or an energy-restricted diet (30% of maintenance requirements) for 28 d. This regime of underfeeding resulted in a 24% reduction in body mass (P < 0.001) and a 36% reduction in the mass of the semitendinosus muscles relative to controls (P < 0.001) by day 28. The concentrations of MSV and IGF1 messenger RNA (mRNA) were reduced (both P < 0.001), but myostatin mRNA was not altered in semitendinosus muscles. Unlike the reduced expression of mRNA, the abundance of MSV protein was increased (P < 0.05) and there was no change in the abundance of myostatin protein. Our results suggest that undernutrition for 28 d decreases the signaling of myostatin by increasing the abundance of MSV protein. Although this action may reduce the growth inhibitory activity of myostatin, it cannot prevent the loss of growth of skeletal muscles during undernutrition.