Vagally Mediated Gut-Brain Relationships in Appetite Control-Insights from Porcine Studies

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.

Bilateral Subdiaphragmatic Vagal Nerve Stimulation Using a Novel Waveform Decreases Body Weight, Food Consumption, Adiposity, and Activity in Obesity-Prone Rats

“…Several studies have found that VNS promotes reduced food intake, causes weight loss, and reduces cravings and appetite [ 15 , 25 – 33 ]. VNS has been associated with reduced plasma glucose, cholesterol, visceral fat, and blood pressure [ 34 ].…”

Appetite and Satiety Control—Contribution of Gut Mechanisms

“…Page summarises current knowledge about the transmission of gastrointestinal luminal, meal-related signals to the brain via the vagus nerve, the modulatory role of circadian rhythms on vagal responsiveness to luminal signals and the influences of obesity and light cycle disruptions—the latter simulating shift-work [ 12 ]. Malbert addresses vagally mediated gut–brain relationships, focusing on important insights derived from studies in pigs [ 13 ], particularly in relation to the sensing of information from the stomach, intestines and portal vein by vagal afferents and the central processing of this information, as evaluated by sophisticated imaging techniques. DiPatrizio summarises the evidence that supports an important modulatory role for endocannabinoids in transmitting signals along the gut-brain axis via direct and indirect interactions with vagal afferents [ 14 ].…”