Blood lactate functions as a signal for enhancing fatty acid metabolism during exercise via TGF-ß in the brain.

Moderate-intensity running (treadmill velocity of 21 m/min) increased blood lactate and actived transforming growth factor-ß (TGF-ß) concentration in rat cerebrospinal fluid (CSF). On the other hand, low-intensity running (15 m/min) did not increase blood lactate and caused no change in CSF TGF-ß. Intraperitoneal (i.p.) administration of lactate to anesthetized rats caused an increase in blood lactate similar to that observed after a 21 m/min running exercise and increased the level of active TGF-ß in CSF. Intraperitoneal administration of lactate at the same dose to awake and unrestricted rats caused a decrease in the respiratory exchange ratio, that is, enhancement of fatty acid oxidation and depression of spontaneous motor activity (SMA). Given that intracisternal administration of TGF-ß to rats has been reported to enhance fatty acid metabolism and to depress SMA, we surmise that the observed changes caused by i.p. lactate administration in this study were mediated, at least in part, by TGF-ß in the brain.

Increased noradrenergic activity in the ventromedial hypothalamus during treadmill running in rats.

Physical exercise dramatically increases the energy expenditure of animals. In terms of energy substrate, at the onset of exercise, the contribution of carbohydrates to the energy expenditure is relatively predominant, and decreases gradually with the progression of exercise, while fat consumption increases progressively. The ventromedial hypothalamus (VMH) is a nucleus in the hypothalamus that regulates whole body energy metabolism via the sympathetic nervous system. Some reports have indicated that noradrenergic projections to the VMH are involved in energy metabolism during exercise. However, it is not clear whether exercise influences the activity of noradrenergic projections to the VMH. We hypothesize that during exercise, noradrenergic neurons projecting to the VMH are activated, and play an important part in enhancing fat oxidation. To test this hypothesis, we used in vivo microdialysis to investigate the effect of exercise on the activity of monoaminergic (noradrenaline: NA, dopamine: DA, serotonin: 5-HT) neurons projecting to the VMH of rats. Rats were subjected to running at 15 m/min (incline 3 degrees) for 60 min. During treadmill running, noradrenergic and dopaminergic activities increased significantly in the VMH. Extracellular 5-HT concentrations in the VMH did not change during treadmill running at the exercise intensity. Given the known effects of NA in the VMH on energy metabolism, our results suggest that the increase in noradrenergic activity in the VMH is related to the enhancement of fat oxidation during exercise.