Erythropoietin induces a shift of muscle phenotype from fast glycolytic to slow oxidative

Sedentary and trained rat groups were studied. Each of these groups was either erythropoietin or placebo treated. Erythropoietin treatment increased significantly all haematological parameters studied. Training per se failed to modify haematological parameters. In a second time, we studied the specific activity of several oxidative enzymes in three different muscles. In sedentary rats, erythropoietin treatment increased significantly the specific activities of cytochrome c oxidase and L-3-hydroxyacyl CoA dehydrogenase in the soleus and those of L-3-hydroxyacyl CoA dehydrogenase and phosphofructokinase in both locomotor muscles. Training increased the oxidative enzymes activities in all muscles studied. In trained rats, effects of erythropoietin and training on oxidative enzymes activities were additive. In all erythropoietin treated muscles, the expression of slow twitch myosin light chains and oxidative myosin heavy chains increased. A similar phenomenon took place in all trained groups for light chains and in placebo treated trained rats for heavy chains. In trained groups, the effects of the hormone and of training were additive. Our results suggest strongly that two different mechanisms are involved in the response of skeletal muscles to erythropoietin treatment and to endurance training and probably whole body endurance is affected by erythropoietin treatment by an increase of oxygenation of all tissues.