Central Neurocircuits Regulating Food Intake in Response to Gut Inputs—Preclinical Evidence

The regulation of energy balance requires the complex integration of homeostatic and hedonic pathways, but sensory inputs from the gastrointestinal (GI) tract are increasingly recognized as playing critical roles. The stomach and small intestine relay sensory information to the central nervous system (CNS) via the sensory afferent vagus nerve. This vast volume of complex sensory information is received by neurons of the nucleus of the tractus solitarius (NTS) and is integrated with responses to circulating factors as well as descending inputs from the brainstem, midbrain, and forebrain nuclei involved in autonomic regulation. The integrated signal is relayed to the adjacent dorsal motor nucleus of the vagus (DMV), which supplies the motor output response via the efferent vagus nerve to regulate and modulate gastric motility, tone, secretion, and emptying, as well as intestinal motility and transit; the precise coordination of these responses is essential for the control of meal size, meal termination, and nutrient absorption. The interconnectivity of the NTS implies that many other CNS areas are capable of modulating vagal efferent output, emphasized by the many CNS disorders associated with dysregulated GI functions including feeding. This review will summarize the role of major CNS centers to gut-related inputs in the regulation of gastric function with specific reference to the regulation of food intake.

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The Role of the Dorsal Vagal Complex and the Vagus Nerve in Feeding Effects of Melanocortin-3/4 Receptor Stimulation*

Endocrinology ◽

10.1210/endo.141.4.7410 ◽

2000 ◽

Vol 141 (4) ◽

pp. 1332-1337 ◽

Cited By ~ 89

Author(s):

Diana L. Williams ◽

Joel M. Kaplan ◽

Harvey J. Grill

Keyword(s):

Food Intake ◽

Vagus Nerve ◽

Messenger Rna ◽

Motor Nucleus ◽

Dorsal Vagal Complex ◽

Dorsal Motor Nucleus ◽

Ventricular Response ◽

Feeding Effects ◽

Diet Intake

Abstract Fourth intracerebroventricular (4th-icv) administration of the melanocortin-3/4 receptor (MC3/4-R) agonist, MTII, reduces food intake; the antagonist, SHU9119, increases feeding. The dorsal motor nucleus of the vagus nerve (DMX) contains the highest density of MC4-R messenger RNA in the brain. To explore the possibility that the DMX contributes to 4th-icv MC4-R effects, we delivered doses of MTII and SHU9119 that are subthreshold for ventricular response unilaterally through a cannula centered above the DMX. MTII markedly suppressed 2-h (50%), 4-h (50%), and 24-h (33%) intake. Feeding was significantly increased 4 h (50%) and 24 h (20%) after SHU9119 injections. These results suggest that receptors in the DMX, or the dorsal vagal complex more generally, underlie effects obtained with 4th-icv administration of these ligands. We investigated possible vagal mediation of 4th-icv MTII effects by giving the agonist to rats with subdiaphragmatic vagotomy. MTII suppressed 2-, 4-, and 24-h liquid diet intake (∼80%) to the same extent in vagotomized and surgical control rats. We conclude that stimulation or antagonism of MC3/4-Rs in the dorsal vagal complex yields effects on food intake that do not require an intact vagus nerve.

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Glutamatergic plasticity within neurocircuits of the dorsal vagal complex and the regulation of gastric functions

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00014.2021 ◽

2021 ◽

Author(s):

Courtney Clyburn ◽

Kirsteen N Browning

Keyword(s):

Food Intake ◽

Energy Homeostasis ◽

Intestinal Secretion ◽

Motor Nucleus ◽

Glutamatergic Transmission ◽

Gi Tract ◽

Dorsal Motor Nucleus ◽

Efferent Neurons ◽

Rapid Transmission

The meticulous regulation of the gastrointestinal (GI) tract is required for the co-ordination of gastric motility and emptying, intestinal secretion, absorption, and transit as well as for the overarching management of food intake and energy homeostasis. Disruption of GI functions is associated with the development of severe GI disorders as well as the alteration of food intake and caloric balance. Functional GI disorders as well as the dysregulation of energy balance and food intake are frequently associated with, or result from, alterations in the central regulation of GI control. The faithful and rapid transmission of information from the stomach and upper GI tract to second order neurons of the nucleus of the tractus solitarius (NTS) relies on the delicate modulation of excitatory glutamatergic transmission, as does the relay of integrated signals from the NTS to parasympathetic efferent neurons of the dorsal motor nucleus of the vagus (DMV). Many studies have focused on understanding the physiological and pathophysiological modulation of these glutamatergic synapses, although their role in the control and regulation of GI functions has lagged behind that of cardiovascular and respiratory functions. The purpose of this review is to examine the current literature exploring the role of glutamatergic transmission in the DVC in the regulation of Gl functions.

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The contribution of afferent signals from the liver to metabolic regulation during exercise

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y02-137 ◽

2002 ◽

Vol 80 (11) ◽

pp. 1035-1044 ◽

Cited By ~ 8

Author(s):

Jean-Marc Lavoie

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Blood Glucose ◽

Food Intake ◽

Vagus Nerve ◽

Metabolic Regulation ◽

Vagal Activity ◽

The Central Nervous System ◽

Response To Exercise

The crucial role of the liver as the only organ to produce glucose used by skeletal muscle during exercise is well known. Since hepatic glucose production is central to blood glucose homeostasis during exercise, it has been postulated that the liver may inform the central nervous system and other organs of its diminishing capacity to produce glucose from glycogen, before blood glucose falls. The sensory role of the liver during exercise would be similar to its role in the control of food intake. As a consequence, the experimental approaches used to test the hypothesis that afferent signals from the liver contribute to metabolic regulation during exercise are inspired by those used to test the same hypothesis in the regulation of food intake. In the present review, two questions are addressed. The existing evidence for the liver's sensory influence on metabolic adjustments to exercise is first reviewed; the nature of the initiating stimuli for the afferent contribution of the liver to physical exercise is discussed thereafter. The hypothetical construct upon which rests the contribution of the liver's afferent signals to metabolic regulation during exercise is that a decrease in liver glycogen or a related metabolic intermediate is sensed by the liver, and the signal is transduced to the central nervous system, most likely through the afferent activity of the hepatic vagus nerve, where it contributes to the orchestration of the metabolic and hormonal responses to exercise. Support in favour of this construct comes mainly from the demonstration that sectioning of the hepatic vagus nerve attenuates the normal hormonal response to exercise. It seems that the liverglucagon axis is particularly responsive to this reflex activation. In other respects, the hepatic mechanism responsible for linking the metabolic activity in the liver to an afferent signal capable of regulating the metabolic response to exercise remains speculative. Substrates or derivatives of substrate oxidation, energy-related compounds (ATP and Pi), or changes in cell volume may all be related to changes in transmembrane potential in the liver cell, which according to the "potentiostatic" theory would determine the afferent vagal activity. Key words: hepatic vagotomy, insulin, glucagon, portal infusion, metabolic regulation.

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NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus Mediates the Enhancement of Gastric Motility by Stimulating ST36

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/438460 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

Xinyan Gao ◽

Yongfa Qiao ◽

Baohui Jia ◽

Xianghong Jing ◽

Bin Cheng ◽

...

Keyword(s):

Synaptic Transmission ◽

Gastric Motility ◽

Low Frequency ◽

Synaptic Activity ◽

Motor Nucleus ◽

Dorsal Motor Nucleus ◽

Vagal Reflex ◽

Precise Molecular Mechanism ◽

Lines Of Evidence

Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). We also identified that suppression of presynapticμ-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36.

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Direct amygdaloid projections to the dorsal motor nucleus of the vagus nerve: a light and electron microscopic study in the rat

Brain Research ◽

10.1016/0006-8993(83)91182-4 ◽

1983 ◽

Vol 280 (1) ◽

pp. 143-147 ◽

Cited By ~ 42

Author(s):

Yoshiki Takeuchi ◽

Sachi Matsushima ◽

Ryotaro Matsushima ◽

David A. Hopkins

Keyword(s):

Vagus Nerve ◽

Microscopic Study ◽

Electron Microscopic Study ◽

Motor Nucleus ◽

Electron Microscopic ◽

Dorsal Motor Nucleus

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NMDA Receptors of Gastric-Projecting Neurons in the Dorsal Motor Nucleus of the Vagus Mediate the Regulation of Gastric Emptying by EA at Weishu (BL21)

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/583479 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Xin Zhang ◽

Bin Cheng ◽

Xianghong Jing ◽

Yongfa Qiao ◽

Xinyan Gao ◽

...

Keyword(s):

Gastric Emptying ◽

Nmda Receptor ◽

Ampa Receptor ◽

Gastrointestinal Motility ◽

Kynurenic Acid ◽

Basic Mechanism ◽

Motor Nucleus ◽

Dorsal Motor Nucleus ◽

Lines Of Evidence

A large number of studies have been conducted to explore the efficacy of electroacupuncture (EA) for the treatment of gastrointestinal motility. While several lines of evidence addressed the basic mechanism of EA on gastrointestinal motility regarding effects of limb and abdomen points, the mechanism for effects of the back points on gastric motility still remains unclear. Here we report that the NMDA receptor (NMDAR) antagonist kynurenic acid inhibited the gastric emptying increase induced by high-intensity EA at BL21 and agonist NMDA enhanced the effect of the same treatment. EA at BL21 enhanced NMDAR, but not AMPA receptor (AMPAR) component of miniature excitatory postsynaptic current (mEPSC) in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). In sum, our data demonstrate an important role of NMDAR-mediated synaptic transmission of gastric-projecting DMV neurons in mediating EA at BL21-induced enhancement of gastric emptying.

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Load-Regulating Mechanisms in Gait and Posture: Comparative Aspects

Physiological Reviews ◽

10.1152/physrev.2000.80.1.83 ◽

2000 ◽

Vol 80 (1) ◽

pp. 83-133 ◽

Cited By ~ 333

Author(s):

J. Duysens ◽

F. Clarac ◽

H. Cruse

Keyword(s):

Functional Role ◽

Stance Phase ◽

Force Feedback ◽

Sensory Information ◽

Specific Load ◽

Afferent Activity ◽

Basic Principles ◽

Load Sensing ◽

The Central Nervous System

How is load sensed by receptors, and how is this sensory information used to guide locomotion? Many insights in this domain have evolved from comparative studies since it has been realized that basic principles concerning load sensing and regulation can be found in a wide variety of animals, both vertebrate and invertebrate. Feedback about load is not only derived from specific load receptors but also from other types of receptors that previously were thought to have other functions. In the central nervous system of many species, a convergence is found between specific and nonspecific load receptors. Furthermore, feedback from load receptors onto central circuits involved in the generation of rhythmic locomotor output is commonly found. During the stance phase, afferent activity from various load detectors can activate the extensor part in such circuits, thereby providing reinforcing force feedback. At the same time, the flexion is suppressed. The functional role of this arrangement is that activity in antigravity muscles is promoted while the onset of the next flexion is delayed as long as the limb is loaded. This type of reinforcing force feedback is present during gait but absent in the immoble resting animal.

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The Role of Ankle Proprioception for Balance Control in relation to Sports Performance and Injury

BioMed Research International ◽

10.1155/2015/842804 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 45

Author(s):

Jia Han ◽

Judith Anson ◽

Gordon Waddington ◽

Roger Adams ◽

Yu Liu

Keyword(s):

Sports Injuries ◽

Balance Control ◽

Sensory Information ◽

Proprioceptive Information ◽

Central Processing ◽

Processing Theory ◽

The Central Nervous System ◽

Sports And Exercise ◽

Ankle Proprioception

Balance control improvement is one of the most important goals in sports and exercise. Better balance is strongly positively associated with enhanced athletic performance and negatively associated with lower limb sports injuries. Proprioception plays an essential role in balance control, and ankle proprioception is arguably the most important. This paper reviews ankle proprioception and explores synergies with balance control, specifically in a sporting context. Central processing of ankle proprioceptive information, along with other sensory information, enables integration for balance control. When assessing ankle proprioception, the most generalizable findings arise from methods that are ecologically valid, allow proprioceptive signals to be integrated with general vision in the central nervous system, and reflect the signal-in-noise nature of central processing. Ankle proprioceptive intervention concepts driven by such a central processing theory are further proposed and discussed for the improvement of balance control in sport.

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Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

International Journal of Molecular Sciences ◽

10.3390/ijms21072568 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2568

Author(s):

Ujendra Kumar ◽

Sneha Singh

Keyword(s):

Food Intake ◽

Hormonal Regulation ◽

Critical Role ◽

Eating Behaviour ◽

Peripheral Tissues ◽

Complex Process ◽

The Many ◽

The One ◽

Food Seeking

Obesity is one of the major social and health problems globally and often associated with various other pathological conditions. In addition to unregulated eating behaviour, circulating peptide-mediated hormonal secretion and signaling pathways play a critical role in food intake induced obesity. Amongst the many peptides involved in the regulation of food-seeking behaviour, somatostatin (SST) is the one which plays a determinant role in the complex process of appetite. SST is involved in the regulation of release and secretion of other peptides, neuronal integrity, and hormonal regulation. Based on past and recent studies, SST might serve as a bridge between central and peripheral tissues with a significant impact on obesity-associated with food intake behaviour and energy expenditure. Here, we present a comprehensive review describing the role of SST in the modulation of multiple central and peripheral signaling molecules. In addition, we highlight recent progress and contribution of SST and its receptors in food-seeking behaviour, obesity (orexigenic), and satiety (anorexigenic) associated pathways and mechanism.

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