Abstract
Signals arising from the upper part of the gut are essential for the regulation of food intake, particularly satiation. This information is supplied to the brain partly by vagal nervous afferents. The porcine model, because of its sizeable gyrencephalic brain, omnivorous regimen, and comparative anatomy of the proximal part of the gut to that of humans, has provided several important insights relating to the relevance of vagally mediated gut-brain relationships to the regulation of food intake. Furthermore, its large size combined with the capacity to become obese while overeating a western diet makes it a pivotal addition to existing murine models, especially for translational studies relating to obesity. How gastric, proximal intestinal, and portal information relating to meal arrival and transit are encoded by vagal afferents and their further processing by primary and secondary brain projections are reviewed. Their peripheral and central plasticities in the context of obesity are emphasized. We also present recent insights derived from chronic stimulation of the abdominal vagi with specific reference to the modulation of mesolimbic structures and their role in the restoration of insulin sensitivity in the obese miniature pig model.
Highlights
Large animal and murine models have contributed to the understanding of vagally mediated gut-brain relationships since the early recognition of the importance of this pathway for appetite control by Iggo in the UK and Mei [1] in France initially in cats [2] and subsequently in sheep [3]
In the pig, obesity-induced insulin resistance leads to functional portal denervation with marked suppression of vagal sensitivity to portal glucose
The latter appears to be the consequence of a reduction in the density of glucagon-like peptide-1 receptor (GLP-1r), as indicated by diminished GLP-1r binding potential in obese insulin-resistant animals [79]
Summary
Large animal and murine models have contributed to the understanding of vagally mediated gut-brain relationships since the early recognition of the importance of this pathway for appetite control by Iggo in the UK and Mei [1] in France initially in cats [2] and subsequently in sheep [3]. Meaningful information from the time interval between two consecutive meals cannot be obtained, which is not an index of satiety but rather a reflection of the boredom of the animal These limitations were overcome by the incorporation of several modifications controlling the access to the trough using a vertical hatch and allowing the remains of the meal to be removed immediately before the initiation of a new meal by capsizing the trough. A an index of satiety but rather a reflection of the boredom of the animal This concept is further supported by creating actual diabetes in the obese miniature pig after the additional administration of a small dose of streptozotocin that, alone, is unable to be effective in lean animals [12]
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