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

Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan

Submitted 29 May 2006 ; accepted in final form 23 June 2006

We have previously reported that the concentration of transforming growth factor- (TGF-) 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-. These results led us to postulate that TGF- 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- activity in rat brain by intracisternal administration of anti-TGF- antibody or SB-431542, an inhibitor of the type 1 TGF- 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- 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- 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- 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- receptor signal transduction system.

central nervous system; energy metabolism; respiratory exchange ratio; activin receptor-like kinase 5; corticotropin-releasing factor

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				T. Shibakusa, W. Mizunoya, Y. Okabe, S. Matsumura, Y. Iwaki, A. Okuno, K. Shibata, K. Inoue, and T. Fushiki Transforming growth factor-beta in the brain is activated by exercise and increases mobilization of fat-related energy substrates in rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1851 - R1861. [Abstract] [Full Text] [PDF]