Transforming growth factor-beta in the brain regulates fat metabolism during endurance exercise.

We have previously reported that the concentration of transforming growth factor-beta (TGF-beta) increases in the cerebrospinal fluid of rats during exercise and that there is an increase in whole body fat oxidation following the intracisternal administration of TGF-beta. These results led us to postulate that TGF-beta in the brain regulates the enhancement of fatty acid oxidation during exercise. To test this hypothesis, we carried out respiratory gas analysis during treadmill running following the inhibition of TGF-beta activity in rat brain by intracisternal administration of anti-TGF-beta antibody or SB-431542, an inhibitor of the type 1 TGF-beta receptor. We found that each reagent partially blocked the increase in the fatty acid oxidation. We also compared the plasma concentrations of energy substrates in the group administered anti-TGF-beta antibody and the control group during running. We found that the plasma concentrations of nonesterified fatty acids and ketone bodies in the group administered anti-TGF-beta antibody were lower than in the control group at the end of running. In the same way, we carried out respiratory gas analysis during treadmill running after depressing corticotropin-releasing factor activity in the brain using intracisternal administration of astressin, an inhibitor of the corticotropin-releasing factor receptor. However, there were no significant differences in respiratory exchange ratio or oxygen consumption in moderate running (60% maximum oxygen consumption). These results suggest that brain TGF-beta has a role in enhancing fatty acid oxidation during endurance exercise and that this regulation is executed at least partly via the type 1 TGF-beta receptor signal transduction system.