Disruption of the light cycle ablates diurnal rhythms in gastric vagal afferent mechanosensitivity

Abstract

BACKGROUND:Gastric vagal afferents (GVAs) respond to mechanical stimulation, initiating satiety. These afferents exhibit diurnal fluctuations in mechanosensitivity, facilitating food intake during the dark phase in rodents. In humans, desynchrony of diurnal rhythms (eg, shift work) is associated with a higher risk of obesity. To test the hypothesis that shift work disrupts satiety signaling, the effect of a rotating light cycles on diurnal rhythms in GVA mechanosensitivity in lean and high-fat diet (HDF)-induced obese mice was determined. METHODS:Male C57BL/6 mice were fed standard laboratory diet (SLD) or HFD for 12 weeks. After 4 weeks, mice were randomly allocated to a normal light (NL; 12 hour light: 12 hour dark; lights on at zeitgeber time [ZT] 0) or rotating light (RL; 3-day NL cycle, 4-day reversed light cycle [lights on: ZT12] repeated) cycle for 8 weeks. At week 12, eight mice from each group were housed in metabolic cages. After 12 weeks, ex vivo GVA recordings were taken at 3 hour intervals starting at ZT0. KEY RESULTS:SLD-RL and HFD-RL gained more weight compared to SLD-NL and HFD-NL mice, respectively. Gonadal fat pad mass was higher in SLD-RL compared to SLD-NL mice. In SLD-NL mice, tension and mucosal receptor mechanosensitivity exhibited diurnal rhythms with a peak at ZT9. These rhythms were lost in SLD-RL, HFD-NL, and HFD-RL mice and associated with dampened diurnal rhythms in food intake. CONCLUSIONS & INFERENCES:GVA diurnal rhythms are susceptible to disturbances in the light cycle and/or the obese state. This may underpin the observed changes in feeding behavior.