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.

Rhythmic neuronal activities of the rat nucleus of the solitary tract are impaired by high‐fat diet – implications for daily control of satiety

“…In this design, neuronal activity recorded in the NTS reflects both intrinsic circadian drive as well as feedback from behavioural and physiological processes such as that arising from consumption and ingestion preceding the time of cull. Here we show, that under CD, the NTS activity peaks at late day (ZT11) confirming our recent finding in mice fed standard laboratory diet (Chrobok et al, 2020) and coinciding with the acrophase in the circadian rhythm of vagal afferent activities (Kentish et al, 2016(Kentish et al, , 2019. This daily variation in CD rats is broadly consistent with rhythm of Period clock gene expression in the rodent NTS reported by a number of groups (Herichová et al, 2007;Kaneko et al, 2009;Chrobok et al, 2020;Paul et al, 2020).…”

“…2020) and coinciding with the acrophase in the circadian rhythm of vagal afferent activities (Kentish et al . 2016, 2019). This daily variation in CD rats is broadly consistent with the rhythm of the Period clock gene expression in the rodent NTS as reported by a number of groups (Herichová et al .…”

Daily changes in neuronal activities of the dorsal motor nucleus of the vagus under standard and high‐fat diet

“…To our knowledge, circadian rhythmicity of efferent vagal activity has not yet been reported, but the afferent branch of vagus nerve exhibits daily and circadian properties. The somas of sensory vagal neurons are localised in nodose ganglia and these demonstrate rhythmic clock gene expression as well as a daytime (ZT6-9) peak in mechanosensitivity (Kentish et al 2013(Kentish et al , 2016(Kentish et al , 2019. These observations raise the possibility that daily variation in DMV molecular and neuronal activity is dependent on recurrent circadian input from other DVC structures as well as signals from the peripheral nervous system.…”

“…The somas of sensory vagal neurons are localised in nodose ganglia and these demonstrate rhythmic clock gene expression as well as a daytime (ZT6‐9) peak in mechanosensitivity (Kentish et al . 2013, 2016, 2019). These observations raise the possibility that daily variation in DMV molecular and neuronal activity is dependent on recurrent circadian input from other DVC structures as well as signals from the peripheral nervous system.…”

Jetlagged microbiota: A problem for gut and metabolic function

“…1 However, when these circadian rhythms are disrupted, as in jetlag models, food intake patterns are also disrupted leading to a loss of diurnal rhythms in food intake and a 'grazing-like' behaviour. 1,3 As stated the gastrointestinal tract can also be entrained by food intake and can be uncoupled from the SCN using time restricted feeding protocols, such as restricted feeding during the natural sleep phase. 2 This raises the question of whether the changes in food intake patterns are driving changes in gastrointestinal rhythmicity or disruption of gastrointestinal clocks is changing food intake patterns.…”