Gastrointestinal Vagal Afferents and Food Intake: Relevance of Circadian Rhythms

Abstract

Gastrointestinal vagal afferents (VAs) play an important role in food intake regulation, providing the brain with information on the amount and nutrient composition of a meal. This is processed, eventually leading to meal termination. The response of gastric VAs, to food-related stimuli, is under circadian control and fluctuates depending on the time of day. These rhythms are highly correlated with meal size, with a nadir in VA sensitivity and increase in meal size during the dark phase and a peak in sensitivity and decrease in meal size during the light phase in mice. These rhythms are disrupted in diet-induced obesity and simulated shift work conditions and associated with disrupted food intake patterns. In diet-induced obesity the dampened responses during the light phase are not simply reversed by reverting back to a normal diet. However, time restricted feeding prevents loss of diurnal rhythms in VA signalling in high fat diet-fed mice and, therefore, provides a potential strategy to reset diurnal rhythms in VA signalling to a pre-obese phenotype. This review discusses the role of the circadian system in the regulation of gastrointestinal VA signals and the impact of factors, such as diet-induced obesity and shift work, on these rhythms.

Keywords: circadian; food intake; gastrointestinal tract; vagal afferents.

Figure 1

Schematic of the wall of the gastrointestinal tract with the location of the receptive fields of subclasses of gastrointestinal vagal afferents (VAs), including mechanosensitive (mucosal stroking) and/or chemosensitive mucosal afferents (Black), intraganglionic laminar endings (IGLEs, tension receptors; Purple), stretch sensitive intramuscular arrays (IMAs, stretch receptors; Green) and tension-mucosal afferents (Brown; sensitive to mucosal stroking and stretch). Chemosensing occurs via specialized enteroendocrine cells (EECs) that express nutrient receptors (NS) which when activated initiate an intracellular process culminating in: (1) the release of gut hormones, such as cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1) which subsequently act on peripheral VA terminals; or (2) the release of a neurotransmitter, such as glutamate, directly onto VA endings via neuropods that protrude from the basolateral surface of EECs.

Figure 2

Schematic of the relationship between energy demand (e.g., during the active dark phase (dark grey region) verses inactive light phase (light blue region)), gastric vagal afferent (VA) sensitivity to food related stimuli (pink line) and food intake and meal size in mice. During the light phase the mice are resting and energy demand is low. Further, gastric VA sensitivity is high and associated with reduced food intake and meal size. Conversely, during the dark phase mice are active and consequently energy demand is high. In addition, gastric VA sensitivity is low and associated with increased food intake and meal size.

Figure 3

Schematic of the effect of circadian desynchrony on diurnal gastric vagal afferent (VA) responses to food related stimuli (e.g., stretch or mucosal stroking) in mice. On a normal standard laboratory diet (SLD) gastric VAs display diurnal rhythms in sensitivity to food related stimuli, with associated diurnal rhythms in food intake. In high fat diet-induced obese mice and/or mice exposed to a rotating light cycle diurnal rhythms in gastric VA responses to food related stimuli are lost and associated with a disruption in diurnal food intake patterns. High fat diet-fed mice exposed to a time restricted feeding (TRF) protocol, where food is restricted to the 12 h light phase or 12 h dark phase, retain diurnal rhythms in gastric VA responses to food related stimuli.