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.

tVNS Increases Liking of Orally Sampled Low-Fat Foods: A Pilot Study

“…We also observed that tVNS did not change liking or wanting for stimuli varying in sugar content. This is in line with the observation that vagal deafferentation of the gut results in increased food intake after a fat but not sugar preload (McDougle et al, 2020), and may suggest a more prominent role for the vagus nerve in signaling fat content to the brain. However, it is also possible that the fixed order of non-fatty sweet Jell-O samples presentation after fatty puddings samples may have worked against observing effects on sweetness perception, as a reduction in fat levels may result in a reduction of perceived sweetness (Wiet et al, 1993;Biguzzi et al, 2014).…”

The Phantom Satiation Hypothesis of Bariatric Surgery

“…At the same time, vagotomy-induced overeating is often transient, presumably due to compensatory changes at the central level ( Walls et al, 1995 ; Chavez et al, 1997 ; Phillips and Powley, 1998 ; Zafra et al, 2003 ; Reidelberger et al, 2014 ). Instead, in normal-weight animals, long-term vagotomy and deafferentation have been reported to result in animals eating smaller meals, with some degree of anorexia and weight loss ( Mordes et al, 1979 ; Sclafani and Kramer, 1985 ; Kraly et al, 1986 ; Erecius et al, 1996 ; Leonhardt et al, 2004 ; Powley et al, 2005a ; McDougle et al, 2020 ). Interestingly, eating smaller meals post-vagotomy is often compensated by more frequent meals, further suggesting significant brain adaptations ( Powley et al, 2005a ).…”

“…It has often been argued, with good reasons, that vagotomies, especially when vagal (motor) efferents are involved, are difficult to interpret because of secondary dysmotility, malaise, and dyspepsia ( Sclafani et al, 1981 ; McDougle et al, 2020 ). At the same time, the latter factors could not entirely account for reduced food intake and weight loss ( Mordes et al, 1979 ; Sclafani and Kramer, 1985 ).…”

Ghrelin signaling regulates feeding behavior, metabolism, and memory through the vagus nerve

“…However, we did not find changes in Mch1r nor Cb1r gene expression in VAN GHSR KD rats compared with controls, suggesting that dysregulation of these receptors is not contributing to the meal pattern changes observed. Notably, ablation of cholecystokinin (CCK) receptorexpressing VAN, which overlap substantially with GHSR-positive VAN [9], produces similar increases in meal frequency without affecting meal size [41]. While CCKR expression was not measured in the present study, the possibility that GHSR and CCKR interact in VAN to influence meal frequency is unlikely given that VAN GHSR KD did not affect VAN neural responses to gut-restricted CCK.…”