Transforming growth factor-β in the brain is activated by exercise and increases mobilization of fat-related energy substrates in rats

We have recently reported that inhibition of transforming growth factor (TGF)-β in the brain reduced fat-related energy substrates concentrations in response to exercise. We investigated the relevance between the mobilization of fat-related energy substrates (nonesterified fatty acid and ketone bodies) during exercise and the effects of TGF-β in the brain. Low-intensity exercise was simulated by contraction of the hindlimbs, induced by electrical stimulation at 2 Hz in anesthetized rats (Sim-Ex). As with actual exercise, it was confirmed that mobilization of carbohydrate-related energy substrates (glucose and lactic acid) occurred immediately after the onset of Sim-Ex, and mobilization of fat-related energy substrates followed thereafter. The timing of mobilization of fat-related substrates corresponded to that of the increase in TGF-β in cerebrospinal fluid (CSF) in Sim-Ex. The level of TGF-β in CSF significantly increased after 10 min of Sim-Ex and remained elevated until 30 min of Sim-Ex. Intracisternal administration of TGF-β caused rapid mobilization of fat-related energy substrates. Meanwhile, there were no effects on the changes in carbohydrate-related substrates. The levels of catecholamines were slightly elevated after TGF-β administration, and, although not significantly in statistical terms, we consider that at least a part of TGF-β signal was transducted via the sympathetic nervous system because of these increases. These data indicate that TGF-β in the brain is closely related to the mobilization of fat-related energy substrates during low-intensity exercise. We hypothesized that the central nervous system plays a role in the regulation of energy metabolism during low-intensity exercise and this may be mediated by TGF-β.