Intact vagal gut-brain signalling prevents hyperphagia and excessive weight gain in response to high-fat high-sugar diet

Abstract

Aim: The tools that have been used to assess the function of the vagus nerve lack specificity. This could explain discrepancies about the role of vagal gut-brain signalling in long-term control of energy balance. Here we use a validated approach to selectively ablate sensory vagal neurones that innervate the gut to determine the role of vagal gut-brain signalling in the control of food intake, energy expenditure and glucose homoeostasis in response to different diets.

Methods: Rat nodose ganglia were injected bilaterally with either the neurotoxin saporin conjugated to the gastrointestinal hormone cholecystokinin (CCK), or unconjugated saporin as a control. Food intake, body weight, glucose tolerance and energy expenditure were measured in both groups in response to chow or high-fat high-sugar (HFHS) diet. Willingness to work for fat or sugar was assessed by progressive ratio for orally administered solutions, while post-ingestive feedback was tested by measuring food intake after an isocaloric lipid or sucrose pre-load.

Results: Vagal deafferentation of the gut increases meal number in lean chow-fed rats. Switching to a HFHS diet exacerbates overeating and body weight gain. The breakpoint for sugar or fat solution did not differ between groups, suggesting that increased palatability may not drive HFHS-induced hyperphagia. Instead, decreased satiation in response to intra-gastric infusion of fat, but not sugar, promotes hyperphagia in CCK-Saporin-treated rats fed with HFHS diet.

Conclusions: We conclude that intact sensory vagal neurones prevent hyperphagia and exacerbation of weight gain in response to a HFHS diet by promoting lipid-mediated satiation.

Keywords: fat; obesity; palatability; post-ingestive; sugar; vagus nerve.