PT  - JOURNAL ARTICLE
AU  - Stephen J. Kentish
AU  - George Hatzinikolas
AU  - Hui Li
AU  - Claudine A Frisby
AU  - Gary A. Wittert
AU  - Amanda J. Page
TI  - Time restricted feeding prevents ablation of diurnal rhythms in gastric vagal afferent mechanosensitivity observed in high fat diet-induced obese mice
AID  - 10.1523/JNEUROSCI.0052-18.2018
DP  - 2018 May 14
TA  - The Journal of Neuroscience
PG  - 0052-18
4099  - http://www.jneurosci.org/content/early/2018/05/14/JNEUROSCI.0052-18.2018.short
4100  - http://www.jneurosci.org/content/early/2018/05/14/JNEUROSCI.0052-18.2018.full
AB  - Mechanosensitive gastric vagal afferents (GVAs) are involved in the regulation of food intake. GVAs exhibit diurnal rhythmicity in their response to food related stimuli allowing time of day specific satiety signalling. This diurnal rhythmicity is ablated in high fat diet (HFD)-induced obesity. Time restricted feeding (TRF) has a strong influence on peripheral clocks. This study aimed to determine whether diurnal patterns in GVA mechanosensitivity are entrained by TRF.Eight-week old male C57BL/6 mice (N=256) were fed a standard laboratory diet (SLD) or HFD for 12wks. After 4wks diet acclimatisation the mice were fed either ad libitum or only during the light (zeitgeber (ZT)0-12) or dark phase (ZT12-24) for 8wks. A subgroup of mice from all conditions (N=8/condition) were placed in metabolic cages. After 12wks, ex vivo GVA recordings were taken at 3h intervals starting at ZT0.HFD mice gained more weight than SLD mice. TRF did not affect weight gain in the SLD mice but decreased weight gain in the HFD mice irrespective of the TRF period. In SLD mice diurnal rhythms in food intake were inversely associated with diurnal rhythmicity of GVA mechanosensitivity. These diurnal rhythms were entrained by the timing of food intake. In HFD mice diurnal rhythms in food intake and diurnal rhythmicity of GVA mechanosensitivity was dampened. Loss of diurnal rhythmicity in HFD-mice was abrogated by TRF.In conclusion, diurnal rhythmicity in GVA responses to food related stimuli can be entrained by food intake. TRF prevents the loss of diurnal rhythmicity that occurs in HFD-induced obesity.SIGNIFICANCE STATEMENTDiurnal control of food intake is vital for maintaining metabolic health. Diet-induced obesity is associated with strong diurnal changes in food intake. Vagal afferents are involved in regulation of feeding behaviour, particularly meal size, and exhibit diurnal fluctuations in mechanosensitivity. These diurnal fluctuations in vagal afferent mechanosensitivity are lost in diet-induced obesity. This study provides evidence that time restricted feeding entrains diurnal rhythmicity in vagal afferent mechanosensitivity in lean and high fat diet-induced (HFD) obese mice and more importantly prevents the loss of rhythmicity in HFD-induced obesity. These data have important implications for the development of strategies to treat obesity.