Voluntary exercise is motivated by ghrelin, possibly related to the central reward circuit

Abstract

We previously reported that voluntary exercise contributed to the amelioration of abnormal feeding behavior with a concomitant restoration of ghrelin production in a rat model of obesity, suggesting a possible relationship between exercise and appetite-regulating hormones. Ghrelin is known to be involved in the brain reward circuits via dopamine neurons related to motivational properties. We investigated the relevance of ghrelin as an initiator of voluntary exercise as well as feeding behavior. The plasma ghrelin concentration fluctuates throughout the day with its peak at the beginning of the dark period in the wild-type (WT) mice with voluntary exercise. Although predominant increases in wheel running activity were observed accordant to the peak of plasma ghrelin concentration in the WT mice, those were severely attenuated in the ghrelin-knockout (GKO) mice under either ad libitum or time-restricted feeding. A single injection of ghrelin receptor agonist brought about and reproduced a marked enhancement of wheel running activity, in contrast to no effect by the continuous administration of the same drug. Brain dopamine levels (DAs) were enhanced after food consumption in the WT mice under voluntary exercise. Although the acceleration of DAs were apparently blunted in the GKO mice, they were dramatically revived after the administration of ghrelin receptor agonist, suggesting the relevance of ghrelin in the reward circuit under voluntary exercise. These findings emphasize that the surge of ghrelin plays a crucial role in the formation of motivation for the initiation of voluntary exercise possibly related to the central dopamine system.

The effects of voluntary wheel running during weight-loss on biomarkers of hepatic lipid metabolism and inflammation in C57Bl/6J mice

“…As result of lower energy stores produced by running wheel exercise during weight-loss, increased dietary intake was observed to compensate for energy depletion. The effects of running wheel exercise on increased energy compensation through dietary intake have been observed in previous wheel running studies ( Copes et al, 2015 ; Mifune et al, 2020 ). In contrast, when examining measures of inflammation following weight-loss, the addition of voluntary wheel running did not provide any observable benefits when compared to weight-loss by diet alone.…”

Unexpected Association of Desacyl-Ghrelin with Physical Activity and Chronic Food Restriction: A Translational Study on Anorexia Nervosa

“…These data are of importance since they emphasise how ghrelin, usually studied for its involvement in the modulation of food intake [ 54 ], is essential to initiate voluntary exercise in parallel to feeding behaviour. Here, in our quantitative food-restricted model, we consolidated the data obtained by Mifune et al in their time-food restricted model [ 53 ]. Indeed, only the food-restricted mice that developed the highest FAA displayed the highest plasma concentrations of both AG and DAG.…”

“…Indeed during 5 days of ABA protocol, GHRS-R1a antagonism inhibited food anticipatory activity (FAA) in mice [ 38 ] and the motivational drive to eat in rats [ 52 ]. Moreover, ghrelin knockout mice exhibited a lower FAA in wheel during a time-restricted feeding protocol and acute administration of GHRP-6, a GHSR-1a agonist, was sufficient to enhance the amount of voluntary exercise in ghrelin KO mice [ 53 ]. This increase of FAA induced by GHRP-6 is mediated by an increase of dopaminergic activity in the nucleus accumbens [ 53 ].…”

“…Moreover, ghrelin knockout mice exhibited a lower FAA in wheel during a time-restricted feeding protocol and acute administration of GHRP-6, a GHSR-1a agonist, was sufficient to enhance the amount of voluntary exercise in ghrelin KO mice [ 53 ]. This increase of FAA induced by GHRP-6 is mediated by an increase of dopaminergic activity in the nucleus accumbens [ 53 ]. These data are of importance since they emphasise how ghrelin, usually studied for its involvement in the modulation of food intake [ 54 ], is essential to initiate voluntary exercise in parallel to feeding behaviour.…”

“…Translational data might be a prerequisite to stress the mechanisms that support a successful recovery in AN. On one hand, ghrelin agonists induced motivation to exercise through activation of the central reward circuit [ 53 ]. Furthermore, central administration of ghrelin enhances exercise through dopamine release in the nucleus accumbens [ 83 ].…”