Inhibition of fatty acid oxidation activates transforming growth factor-beta in cerebrospinal fluid and decreases spontaneous motor activity.
We have previously reported that transforming growth factor (TGF)-beta in the cerebrospinal fluid (CSF) is involved in the mechanism underlying the regulation of spontaneous motor activity (SMA) by the central nervous system after exercise. However, it remained unclear what physiological condition triggers the activation of TGF-beta. We hypothesized that the shortage of energy derived from fatty acid (FA) oxidation observed in the early phase of exercise activated TGF-beta in the CSF. To test this hypothesis, we investigated whether mercaptoacetate (MA), an inhibitor of FA oxidation, could induce an activation of TGF-beta in the CSF and a decrease in SMA. Intraperitoneal (i.p.) administration of MA activated TGF-beta in CSF in rats and depressed SMA; 2-deoxyglucose, an inhibitor of carbohydrate oxidation, on the other hand, depressed SMA but failed to activate CSF TGF-beta. Intracisternal administration of anti-TGF-beta antibody abolished the depressive effect of MA on SMA. We also found that the depression of SMA and the activation of TGF-beta in the CSF by i.p. MA administration were eliminated by vagotomy. Our data suggest that TGF-beta in the CSF is activated by the inhibition of FA oxidation via the vagus nerve and that this subsequently induces depression of SMA.
Fujikawa
Teppei
T
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan.
Fujita
Ryo
R
Iwaki
Yoko
Y
Matsumura
Shigenobu
S
Fushiki
Tohru
T
Inoue
Kazuo
K
D000704:Analysis of Variance; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D004734:Energy Metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013864:Thioglycolates / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000134:cerebrospinal fluid* / Q000378:metabolism; D014630:Vagus Nerve / Q000502:physiology
D004791:Enzyme Inhibitors; D005227:Fatty Acids; D013864:Thioglycolates; D016212:Transforming Growth Factor beta; C017487:2-mercaptoacetate; D003847:Deoxyglucose