Regular exercise augments gut-brain communication and visceral feedback control of appetite

Regular exercise is widely accepted to support long-term body weight management; however, the neurobiological adaptations that contribute to the beneficial effects of habitual physical activity beyond increases in energy expenditure per se remain unclear. Here, we investigated whether regular exercise alters gut-brain communication and visceral feedback control of feeding.

Mice were subjected to regular voluntary wheel running. Energy expenditure and feeding were assessed under basal conditions and following an overnight fast. Nutrients were delivered directly into the stomach by intragastric infusion. Brain-wide responses to intragastric nutrient delivery were assessed using positron emission tomography (PET). Single-cell sequencing and histological analyses were used to determine nutrient-responsive neuronal populations in the caudal brainstem. Genetic associations with body weight were evaluated using GWAS data.

Intragastric nutrient delivery suppressed feeding more strongly in exercising mice. Brain-wide PET revealed enhanced responses to intragastric nutrients in various brain regions. Single-cell sequencing identified several nutrient-responsive caudal brainstem populations, including a previously unrecognized population marked by expression of fibrinogen C domain containing 1 (FIBCD1). Regular exercise selectively enhanced the nutrient-evoked activation of FIBCD1 neurons. Histological analyses demonstrate that FIBCD1 neurons are also present in the human brainstem, and GWAS data suggest a potential relevance of this neuron population to body-weight regulation.

Regular exercise enhances behavioral and brain responses to intragastric nutrient delivery and sensitizes FIBCD1 neurons in the brainstem of mice. These findings reveal an exercise-associated adaptation of gut-brain communication that may contribute to improved matching of caloric intake to energy expenditure.