The vagus nerve, food intake and obesity

doi:10.1016/j.regpep.2007.08.024

Regulatory Peptides

Volume 149, Issues 1–3, 7 August 2008, Pages 15-25

https://doi.org/10.1016/j.regpep.2007.08.024 Get rights and content

Abstract

Food interacts with sensors all along the alimentary canal to provide the brain with information regarding its composition, energy content, and beneficial effect. Vagal afferents innervating the gastrointestinal tract, pancreas, and liver provide a rapid and discrete account of digestible food in the alimentary canal, as well as circulating and stored fuels, while vagal efferents, together with the sympathetic nervous system and hormonal mechanisms, codetermine the rate of nutrient absorption, partitioning, storage, and mobilization. Although vagal sensory mechanisms play a crucial role in the neural mechanism of satiation, there is little evidence suggesting a significant role in long-term energy homeostasis. However, increasing recognition of vagal involvement in the putative mechanisms making bariatric surgeries the most effective treatment for obesity should greatly stimulate future research to uncover the many details regarding the specific transduction mechanisms in the periphery and the inter- and intra-neuronal signaling cascades disseminating vagal information across the neuraxis.

Introduction

There is no doubt that the prevalence of obesity and the metabolic syndrome is rapidly increasing, with abdominal obesity in more than half of the adult US population and a 60% increase of abdominal obesity from 1999–2004 in children [1], [2]. The strong correlation between BMI and development of type 2 diabetes, cardiovascular disease, gall bladder disease, osteoarthritis, sleep, and mental disorders makes it the major health problem.

Current treatment of obesity targets both energy intake and expenditure, and includes dieting and physical exercise (life style changes), as well as surgery, drugs, plant extracts, and many scientifically undocumented remedies. Most of these treatments are not very effective, with a typical maximal weight loss of less than 10%, and not able to stop the epidemic. Obesity surgery is presently the most effective treatment with sustained weight loss of up to 50%. Obesity surgery consists of restricting the capacity of the stomach to accommodate ingested food and/or redirecting the flow of digesta to the lower gut, implicating gut–brain signaling as an important factor in the development and prevention of obesity [3]. The vagus nerve is arguably the most important link between the gut and the brain, and the present review attempts to clarify the role of this nerve in the control of food intake, energy balance, and the development of obesity. Furthermore, some of the literature exploiting stimulation of vagal components as potential obesity treatment is reviewed.

Section snippets

Oral cavity: taste receptors and trigeminal mechanosensors

Gustatory input via taste receptor cells on the tongue and palate is considered most important for guiding food intake and selection (Fig. 1). Although only a minor portion of this information is mediated to the brain by the vagus nerve, the gustatory system is included here because it shares the nucleus tractus solitarius (NTS) and other central processing stations with vagal afferents from the gastrointestinal tract. The gustatory and trigeminal systems act as “gate keepers” at the entrance

Integration of vagal mechanisms within the hindbrain

The brainstem harbors an impressive array of neurons and circuits directly involved in ingestion, digestion, and absorption of food, as well as in utilization of metabolites and fuels. The neural circuits controlling most of these tasks are contained within the brainstem and do not require the forebrain for their execution. Just as for respiration and circulation, other body functions essential for survival, the regulation of nutrient supply is to a large extent autonomically organized within

Evidence for vagal afferents in short- but not long-term control of food intake

Given this impressive breadth of sensory capacities of vagal afferents, one could expect that they play a crucial role in the control of food intake and possibly energy balance. Since vagal afferents transmit predominantly satiety signals from the gut to the brain, they seem important for keeping appetite under control and may help prevent development of obesity.

However, total food intake and body weight are surprisingly impervious to manipulations of vagal integrity. Total abdominal vagotomies

Conclusions

Vagal pathways innervating the gastrointestinal tract, pancreas, and liver are intimately involved in the control of assimilation, storage, mobilization, conversion, and oxidation of macronutrients. Although much is already known about vagal afferent nutrient sensors informing the brain about the short-term availability of energy, many details regarding the specific transduction mechanisms in the periphery and the inter- and intra-neuronal signaling cascades disseminating the sensory

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ReviewThe vagus nerve, food intake and obesity

Abstract

Introduction

Section snippets

Oral cavity: taste receptors and trigeminal mechanosensors

Integration of vagal mechanisms within the hindbrain

Evidence for vagal afferents in short- but not long-term control of food intake

Conclusions

Nutrition

Brain Res Brain Res Rev

Auton Neurosci

J Auton Nerv Syst

Neuroscience

Physiol Behav

Gastroenterology

Physiol Behav

Neuroscience

Auton Neurosci

Physiol Behav

Neuroscience

Auton Neurosci

J Auton Nerv Syst

Peptides

Cell Metab

Peptides

Regul Pept

Brain Res

Regul Pept

Auton Neurosci

Brain Res

J Auton Nerv Syst

Curr Opin Neurobiol

Front Neuroendocrinol

Brain Res Bull

Neuroscience

Horm Behav

Recent trends in waist circumference and waist–height ratio among US children and adolescents

Pediatrics

Increasing trends in waist circumference and abdominal obesity among US adults

Obesity (Silver Spring)

Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution

J Clin Endocrinol Metab

Taste perception and coding in the periphery

Cell Mol Life Sci

Discrete innervation of murine taste buds by peripheral taste neurons

J Neurosci

CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions

J Clin Invest

Vagal and spinal mechanosensors in the rat stomach and colon have multiple receptive fields

Am J Physiol Regul Integr Comp Physiol

Intraganglionic laminar endings are mechano-transduction sites of vagal tension receptors in the guinea-pig stomach

J Physiol

Distribution and structure of vagal afferent intraganglionic laminar endings (IGLEs) in the rat gastrointestinal tract

Anat Embryol (Berl)

Vagal afferent innervation of the rat fundic stomach: morphological characterization of the gastric tension receptor

J Comp Neurol

The stomach is a source of leptin

Nature

Two types of leptin-responsive gastric vagal afferent terminals: an in vitro single-unit study in rats

Am J Physiol

Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve

Eur J Neurosci

Leptin and CCK selectively activate vagal afferent neurons innervating the stomach and duodenum

Am J Physiol Regul Integr Comp Physiol

A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans

Diabetes

Ghrelin receptors in rat and human nodose ganglia: putative role in regulating CB-1 and MCH receptor abundance

Am J Physiol Gastrointest Liver Physiol

Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy

J Clin Endocrinol Metab

Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat

J Neurosci

Luminal amino acid sensing in the rat gastric mucosa

Am J Physiol Gastrointest Liver Physiol

Vagal sensors in the rat duodenal mucosa: distribution and structure as revealed by in vivo DiI-tracing

Anat Embryol (Berl)

Vagal afferent nerve fibres contact mast cells in rat small intestinal mucosa

Neuroimmunomodulation

Vagal afferents innervating the gastrointestinal tract and CCKA-receptor immunoreactivity

Anat Rec

Review
The vagus nerve, food intake and obesity