Mechanosensitive gastric vagal afferents are part of a co-ordinated set of peripheral mechanisms involved in the regulation of food intake. Previously we have shown that (i) gastric vagal afferent response to mechanical stimulation exhibits circadian variation1, and (ii) obesity reduces vagal afferent mechanosensitivity2. However, the effect of obesity on circadian variation of gastric vagal afferent activity is unknown and thus we aimed to determine this.We fed 8 week old male C57BL/6 mice either a standard laboratory diet (SLD; 12% energy from fat, N=48) or high fat diet (HFD; 60% energy from fat, N=48) for 12 weeks then sacrificed mice at 3 hour intervals (N=6/diet/time point) starting at 18:00 (lights off). Stomach contents were measured and single fibre recordings from gastric vagal tension and mucosal receptors were obtained at each time point3. In a separate cohort of SLD and HFD mice (N=8/diet) 13C octanoic acid breath testing studies were performed to determine the gastric emptying rate of a liquid meal at 18:00, 00:00, 06:00 and 12:004.In SLD mice, at 00:00 (N=6) as compared to 12:00 (N=6), stomach contents were 175% greater (p<0.001, one-way ANOVA, Tukey’s post-hoc test), response of tension receptors to tension (3g) was reduced by 60% (p<0.001, one-way ANOVA, Tukey’s post-hoc test) and that of mucosal receptors to stroking (50mg) was reduced by 60% (p<0.001, one-way ANOVA, Tukey’s post-hoc test). In HFD mice circadian variation in stomach contents, vagal afferent mechanosensitivity was minimal. There was little variation in liquid gastric emptying at any time point in either SLD (t½ 28.2±1.1min at 18:00- 38.8±5.2min at 00:00) or HFD mice (t½ 31.9±3.5min at 18:00- 35.0±4.4min at 00:00) (both p>0.05, one-way ANOVA) and there was no difference between SLD and HFD mice (p>0.05, SLD vs. HFD two-way ANOVA, diet effect).In conclusion, HFD induced obesity suppresses circadian variations in gastric vagal afferent mechanosensitivity, which may represent a mechanism which would allow for alterations in daily food intake patterns in obesity.
Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCB047
Poster Communications: High fat diet-induced obesity disrupts circadian variations in gastric vagal afferent satiety signals in mice
S. J. Kentish1, S. Kritas3, G. A. Wittert1, D. J. Kennaway2, A. J. Page1
1. Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia. 2. Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia. 3. Women's & Children's Hospital, Adelaide, South Australia, Australia.
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Where applicable, experiments conform with Society ethical requirements.