Neutralization of tumor necrosis factor reverses age-induced impairment of insulin responsiveness in skeletal muscle of Sprague-Dawley rats.

Between 7 and 14 weeks of age, male Sprague-Dawley (S-D) rats exhibit a substantial increase in adiposity and a corresponding decrease in insulin-stimulated glucose transport in skeletal muscle. In S-D rats aged 3 months, daily administration of goat antimurine tumor necrosis factor (TNF) IgG (anti-TNF; 8 mg, subcutaneously, daily for 7 days) increased insulin-stimulated glucose transport in isolated strips of soleus muscle, compared to controls treated with nonimmune IgG (NI). The TNF content of muscle was markedly higher than that of fat or plasma. Treatment with anti-TNF decreased the mass of inguinal subcutaneous fat and the TNF content of skeletal muscle, but not the TNF content of fat or plasma. Treatment with anti-TNF also produced a nonsignificant trend for reduction in weight gain. Muscle mass and visceral fat mass were unchanged. These data suggest that skeletal muscle pools of TNF may play an important role in the development of insulin resistance.