Diet induced obesity disrupts gastric vagal afferent circadian rhythm (#123)
Many processes including food intake are regulated in a circadian manner1 . Disruption of circadian cycles (e.g. shift workers) increase the risk for developing metabolic conditions, such as obesity and type 2 diabetes2 . Mechanosensitive gastric vagal afferents are part of a co-ordinated set of peripheral mechanisms involved in the regulation of food intake3. Previously we have shown that (i) gastric vagal afferent response to mechanical stimulation exhibits circadian variation, (ii) obesity reduces vagal afferent mechanosensitivity and (iii) instead of potentiating gastric vagal mucosal receptors leptin inhibits tension receptors4 . However, whether the circadian cycle regulates the vagal modulatory effect of leptin and whether diet-induced obesity disrupts circadian variation of gastric vagal afferent activity is unknown.
Therefore, we fed 8 week old female C57BL/6 mice either a standard laboratory diet (SLD; 7% energy from fat, N=12) or high fat diet (HFD; 60% energy from fat, N=12) for 12 weeks. At which time mice were sacrificed at 6 hour intervals starting at 18:00. Stomach contents were measured and single fibre recordings from gastric vagal tension and mucosal receptors were obtained at each time point, in the absence and presence of leptin (1nM)5 .
In SLD mice, at 00:00 as compared to 12:00, stomach contents were 168% greater (p<0.01), response of tension receptors to tension (3g) was reduced by 59% (p<0.01) and that of mucosal receptors to stroking (50mg) was reduced by 62% (p<0.001). Leptin potentiation of mucosal receptor responses to stroking (50mg), were 70% less at 00:00 than 12:00 (p<0.05). In HFD mice circadian variation in stomach contents, vagal afferent mechanosensitivity, and leptin inhibition of tension receptors, was minimal.
In conclusion, HFD induced obesity suppresses circadian variations in gastric vagal afferent mechanosensitivity, responsiveness of tension receptors to leptin and alters food intake patterns.
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- Kentish SJ, O'Donnell TA, Isaacs NJ, Young RL, Li H, Harrington AM, et al. Gastric vagal afferent modulation by leptin is influenced by food intake status. J Physiol. 2013;591:1921-34.
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