Gastric loads and cholecystokinin synergistically stimulate rat gastric vagal afferents

1993 ◽  
Vol 265 (4) ◽  
pp. R872-R876 ◽  
Author(s):  
G. J. Schwartz ◽  
P. R. McHugh ◽  
T. H. Moran
Keyword(s):  
Food Intake ◽  
Vagal Afferents ◽  
Sufficient Information ◽  
Afferent Activity ◽  
Combined Load ◽  
Synergistic Inhibition ◽  
Afferent Fibers ◽  
Inhibit Food Intake ◽  
Vagal Afferent ◽  
Afferent Response

Both gastric preloads and exogenous cholecystokinin (CCK) administration inhibit food intake, and combinations of preloads and CCK suppress feeding to a greater degree than either stimulus delivered alone. A role for the vagus nerve in mediating CCK's inhibition of food intake has been proposed, and gastric vagal afferent fibers respond to both gastric loads and local CCK infusions. To examine whether combined load and CCK stimuli may synergistically augment gastric neural afferent activity at the level of the peripheral vagus, we have examined the gastric vagal afferent responses (n = 8) to a range of gastric saline loads (1, 2, and 3 ml) and exogenous close celiac arterial CCK (10 and 100 pmol) when administered alone or in combination. Gastric loads ineffective in eliciting a significant increase in vagal afferent activity when administered alone became effective when combined with doses of CCK that were subthreshold for the production of a vagal afferent response. Gastric loads that alone were effective in producing a significant vagal afferent response yielded an even greater response when administered in combination with both subthreshold and suprathreshold doses of CCK. These data demonstrate that, in rats, signals produced by combined gastric load and exogenous CCK administration are integrated peripherally and interact synergistically. These results suggest that signals arising from the vagus may provide sufficient information for the synergistic inhibition of food intake produced by combinations of gastric loads and exogenous CCK.

Subdiaphragmatic vagal deafferentation fails to block feeding-suppressive effects of LPS and IL-1 beta in rats

1997 ◽  
Vol 273 (3) ◽  
pp. R1193-R1198 ◽  
Author(s):  
G. J. Schwartz ◽  
C. R. Plata-Salaman ◽  
W. Langhans
Keyword(s):  
Food Intake ◽  
Interleukin 1 ◽  
Glucose Consumption ◽  
Vagal Afferents ◽  
Afferent Pathways ◽  
Afferent Fibers ◽  
Inhibit Food Intake ◽  
Vagal Afferent ◽  
Left Vagus

To evaluate the role of subdiaphragmatic vagal afferent fibers in mediating the inhibition of food intake produced by peripheral administration of bacterial lipopolysaccharide (LPS) and the proinflammatory cytokine interleukin-1 beta (IL-1 beta), we assessed the ability of 100 micrograms/kg ip LPS and 2 micrograms/kg ip human recombinant IL-1 beta to suppress solid food intake during the first 3 and 6 h of the dark cycle in rats with selective vagal rootlet deafferentation (SDA, n = 15) and in sham surgical control rats (Con, n = 17). SDA was produced by a combination of dorsal subdiaphragmatic truncal vagotomy and left vagal afferent rootlet transection as the left vagus enters the caudal brain stem. Both LPS and IL-1 beta significantly suppressed food intake at 3 and 6 h in both Con and SDA rats, and SDA failed to attenuate the LPS- and IL-1 beta-induced reductions in food consumption relative to the suppression seen in controls. Peripheral administration of the gut-brain peptide cholecystokinin (CCK) suppressed 30-min 12.5% liquid glucose consumption in control, but not in SDA rats, consistent with previous demonstrations of the role of subdiaphragmatic vagal afferents in the mediation of CCK satiety. These data demonstrate that subdiaphragmatic vagal afferents are not necessary for the feeding-suppressive actions of peripherally administered LPS and IL-1 beta and suggest that peripheral LPS and IL-1 beta may inhibit food intake via humoral and/or splanchnic visceral afferent pathways.

scholarly journals The common hepatic branch of the vagus is not required to mediate the glycemic and food intake suppressive effects of glucagon-like-peptide-1

2011 ◽  
Vol 301 (5) ◽  
pp. R1479-R1485 ◽  
Author(s):  
Matthew R. Hayes ◽  
Scott E. Kanoski ◽  
Bart C. De Jonghe ◽  
Theresa M. Leichner ◽  
Amber L. Alhadeff ◽  
...  
Keyword(s):  
Food Intake ◽  
Vagal Afferents ◽  
Oral Glucose ◽  
Afferent Fibers ◽  
The Common ◽  
Vagal Afferent ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
And Control ◽  
Hepatic Branch

The incretin and food intake suppressive effects of intraperitoneally administered glucagon-like peptide-1 (GLP-1) involve activation of GLP-1 receptors (GLP-1R) expressed on vagal afferent fiber terminals. Central nervous system processing of GLP-1R-driven vagal afferents results in satiation signaling and enhanced insulin secretion from pancreatic-projecting vagal efferents. As the vast majority of endogenous GLP-1 is released from intestinal l-cells following ingestion, it stands to reason that paracrine GLP-1 signaling, activating adjacent GLP-1R expressed on vagal afferent fibers of gastrointestinal origin, contributes to glycemic and food intake control. However, systemic GLP-1R-mediated control of glycemia is currently attributed to endocrine action involving GLP-1R expressed in the hepatoportal bed on terminals of the common hepatic branch of the vagus (CHB). Here, we examine the hypothesis that activation of GLP-1R expressed on the CHB is not required for GLP-1's glycemic and intake suppressive effects, but rather paracrine signaling on non-CHB vagal afferents is required to mediate GLP-1's effects. Selective CHB ablation (CHBX), complete subdiaphragmatic vagal deafferentation (SDA), and surgical control rats received an oral glucose tolerance test (2.0 g glucose/kg) 10 min after an intraperitoneal injection of the GLP-1R antagonist, exendin-(9–39) (Ex-9; 0.5 mg/kg) or vehicle. CHBX and control rats showed comparable increases in blood glucose following blockade of GLP-1R by Ex-9, whereas SDA rats failed to show a GLP-1R-mediated incretin response. Furthermore, GLP-1(7–36) (0.5 mg/kg ip) produced a comparable suppression of 1-h 25% glucose intake in both CHBX and control rats, whereas intake suppression in SDA rats was blunted. These findings support the hypothesis that systemic GLP-1R mediation of glycemic control and food intake suppression involves paracrine-like signaling on GLP-1R expressed on vagal afferent fibers of gastrointestinal origin but does not require the CHB.

CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents

2005 ◽  
Vol 289 (3) ◽  
pp. R695-R703 ◽  
Author(s):  
E. H. E. M. van de Wall ◽  
P. Duffy ◽  
R. C. Ritter
Keyword(s):  
Vagal Afferents ◽  
Gastric Distension ◽  
Solitary Tract ◽  
C Fibers ◽  
Balloon Distension ◽  
Electrophysiological Responses ◽  
Vagal Afferent ◽  
Fos Expression ◽  
Afferent Response ◽  
And Control

Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhances behavioral and electrophysiological responses to gastric distension in rats and people, we hypothesized that CCK might enhance the vagal afferent response to gastric distension via an action on capsaicin-insensitive vagal afferents. To test this hypothesis, we quantified expression of Fos-like immunoreactivity (Fos) in the dorsal vagal complex (DVC) of capsaicin-treated (Cap) and control rats (Veh), following gastric balloon distension alone and in combination with CCK injection. In Veh rats, intraperitoneal CCK significantly increased DVC Fos, especially in nucleus of the solitary tract (NTS), whereas in Cap rats, CCK did not significantly increase DVC Fos. In contrast to CCK, gastric distension did significantly increase Fos expression in the NTS of both Veh and Cap rats, although distension-induced Fos was attenuated in Cap rats. When CCK was administered during gastric distension, it significantly enhanced NTS Fos expression in response to distension in Cap rats. Furthermore, CCK's enhancement of distension-induced Fos in Cap rats was reversed by the selective CCK-A receptor antagonist lorglumide. We conclude that CCK directly activates capsaicin-sensitive C-type vagal afferents. However, in capsaicin-resistant A-type afferents, CCK's principal action may be facilitation of responses to gastric distension.

Responses of celiac and cervical vagal afferents to infusions of lipids in the jejunum or ileum of the rat

2000 ◽  
Vol 278 (1) ◽  
pp. R34-R43 ◽  
Author(s):  
Alan Randich ◽  
William J. Tyler ◽  
James E. Cox ◽  
Stephen T. Meller ◽  
Gary R. Kelm ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Linoleic Acid ◽  
Single Unit ◽  
Corn Oil ◽  
Body Weight Gain ◽  
Vagal Afferents ◽  
Afferent Activity ◽  
Inhibitory Effects ◽  
Vagal Afferent ◽  
Increased Activity

Multiunit celiac and single-unit cervical recordings of vagal afferents were performed before and during infusions of fatty acids, triglycerides, or saline into either the ileum or jejunum of the rat. In multiunit recordings, lipids increased activity of vagal afferents to a greater extent than saline. The greatest increases in vagal afferent activity resulted from infusions of linoleic acid, conjugated linoleic acid, or oleic acid. The triglycerides, corn oil or Intralipid, were less effective than the fatty acids in affecting vagal afferent activity. Ileal pretreatment with the hydrophobic surfactant Pluronic L-81 significantly attenuated the response of celiac vagal afferents to ileal infusion of linoleic acid. Single-unit recordings of cervical vagal afferents supported the multiunit data in showing lipid-induced increased vagal afferent activity in ∼50% of ileal units sampled and 100% of a limited number of jejunal units sampled. These data demonstrate that free fatty acids can activate ileal and jejunal vagal afferents in the rat, and this effect can be attenuated by pretreatment with a chylomicron inhibitor. These data are consistent with the view that lipid-induced activation of vagal afferents could be a potential substrate for the inhibitory effects of intestinal lipids on gastrointestinal function, food intake, and body weight gain.

Integration of vagal afferent responses to gastric loads and cholecystokinin in rats

1991 ◽  
Vol 261 (1) ◽  
pp. R64-R69 ◽  
Author(s):  
G. J. Schwartz ◽  
P. R. McHugh ◽  
T. H. Moran
Keyword(s):  
Discharge Rate ◽  
Celiac Artery ◽  
Gastric Volume ◽  
Afferent Activity ◽  
Rapid Adaptation ◽  
Discharge Rates ◽  
Group I ◽  
Afferent Fibers ◽  
Vagal Afferent ◽  
Contrast Group

The neurophysiological responses to 2-ml intragastric saline loads and 100-pmol celiac artery infusions of cholecystokinin (CCK) were obtained from 20 vagal afferent fibers in 14 rats. Two groups of fibers were identified. Discharge rates of group I fibers (n = 16) were significantly increased by gastric loading, adapted slowly to maintained gastric volume, and were inhibited by load withdrawal. CCK elicited a significant increase in the discharge rate of these group I fibers. Prior exposure to CCK nearly doubled the response of these fibers to a subsequent gastric load. In contrast, group II fibers (n = 4) increased firing rate only during infusion of a gastric load and showed rapid adaptation and no response to CCK. CCK failed to alter subsequent responses to gastric loads in these fibers. These results 1) demonstrate an integration of signals elicited by exogenous CCK and gastric loads at the level of vagal afferent fibers and 2) imply that aspects of CCK's inhibition of food intake may derive from CCK's ability to mimic and amplify vagal afferent activity provoked by meal-related gastric events.

scholarly journals Deletion of GPR40 fatty acid receptor gene in mice blocks mercaptoacetate-induced feeding

2016 ◽  
Vol 310 (10) ◽  
pp. R968-R974 ◽  
Author(s):  
Ai-Jun Li ◽  
Michael F. Wiater ◽  
Qing Wang ◽  
Stephen Wank ◽  
Sue Ritter
Keyword(s):  
Fatty Acid ◽  
Food Intake ◽  
Receptor Gene ◽  
Treatment Groups ◽  
Metabolic Monitoring ◽  
Afferent Activation ◽  
Inhibit Food Intake ◽  
Vagal Afferent ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

Both increased and decreased fatty acid (FA) availability contribute to control of food intake. For example, it is well documented that intestinal FA reduces feeding by triggering enterondocrine secretion of satietogenic peptides, such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). In contrast, mechanisms by which decreased FA availability increase feeding are not well understood. Over the past three decades substantial research related to FA availability and increased feeding has involved use of the orexigenic compound mercaptoacetate (MA). Because MA reportedly inhibits FA oxidation, it has been assumed that reduced FA oxidation accounts for the orexigenic action of MA. Recently, however, we demonstrated that MA antagonizes G protein-coupled receptor 40 (GPR40), a membrane receptor for long and medium chain FA. We also demonstrated that, by antagonizing GPR40, MA inhibits GLP-1 secretion and attenuates vagal afferent activation by FA. Because both vagal afferent activation and GLP-1 inhibit food intake, we postulated that inhibition of GPR40 by MA might underlie the orexigenic action of MA. We tested this hypothesis using male and female GPR40 knockout (KO) and wild-type (WT) mice. Using several testing protocols, we found that MA increased feeding in WT, but not GPR40 KO mice, and that GPR40 KO mice gained more weight than WT on a high-fat diet. Metabolic monitoring after MA or saline injection in the absence of food did not reveal significant differences in respiratory quotient or energy expenditure between treatment groups or genotypes. These results support the hypothesis that MA stimulates food intake by blocking FA effects on GPR40.

Responses of medullary raphe neurons to electrical and chemical activation of vagal afferent nerve fibers

1993 ◽  
Vol 70 (5) ◽  
pp. 1950-1961 ◽  
Author(s):  
A. R. Evans ◽  
R. W. Blair
Keyword(s):  
Electrical Stimulation ◽  
Chemical Activation ◽  
Vagal Afferents ◽  
Frequency Dependent ◽  
Afferent Fibers ◽  
Vagal Afferent ◽  
Mixed Responses ◽  
Excitatory Responses ◽  
Dose Dependent ◽  
Stimulation Of

1. Various intensities, frequencies, and pulse widths of electrical stimulation of vagal afferent fibers were used to assess the responses of 87 medullary raphe neurons to vagal afferent fiber input in pentobarbital sodium-anesthetized, barodenervated paralyzed cats. Thirty-seven neurons were antidromically activated from the T2-T3 segments of the thoracic spinal cord, and 40 neurons could not be antidromically activated. Neurons were located in the nucleus raphe magnus (79%) and the nucleus raphe obscurus (15%). The remaining 6% of the neurons were not found; however, their locations were comparable in depth and position on the midline with other neurons in the same animals whose locations were identified. 2. The responses of 60 neurons to electrical stimulation of vagal afferent fibers were classified as excitatory (38%), inhibitory (24%), or mixed, (7%). The mixed responses were characterized by excitation at one frequency or intensity and inhibition at another frequency or intensity. The remaining 27 neurons did not clearly respond. 3. The excitatory responses to electrical stimulation of the cervical vagus nerve were intensity and frequency dependent. Inhibitory responses were frequency dependent at lower frequencies of stimulation and both frequency and intensity dependent at higher frequencies. The mixed responses were frequency dependent. Overall, longer pulse widths produced significantly greater responses than shorter pulse widths. 4. Thirty-three neurons were tested for responses to chemical stimulation of vagal afferents with intra-atrial injections of three doses of veratridine. Twenty-one percent were excited, 55% were inhibited, and 6% had mixed responses. For the mixed responses, excitation occurred at one dose and inhibition at another. The remaining 18% of the neurons were unresponsive to veratridine. The excitatory responses were dose dependent, but the inhibitory responses were not. Three doses of phenybiguanide (PBG) were also used to chemically activate vagal afferents in 27 neurons. Eleven percent were excited, 44% were inhibited, and 4% had mixed responses. The remaining 41% were unresponsive to PBG. The excitatory and inhibitory responses were dose dependent. 5. When comparing responses in projection and nonprojection neurons, inhibition was seen significantly more often in projection neurons and excitation in nonprojection neurons. Sixty-three percent of the neurons inhibited by electrical stimulation were raphespinal neurons, and 78% of the neurons excited by vagal stimulation were nonprojection neurons. Similar observations were made with the responses to chemical activation of the vagus. 6. Neurons with lower spontaneous discharge rates were more often excited by vagal stimulation and neurons with higher rates were more often inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)

Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity

2015 ◽  
Vol 308 (5) ◽  
pp. R360-R369 ◽  
Author(s):  
Yusaku Iwasaki ◽  
Yuko Maejima ◽  
Shigetomo Suyama ◽  
Masashi Yoshida ◽  
Takeshi Arai ◽  
...  
Keyword(s):  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Body Weight Gain ◽  
Vagal Afferents ◽  
Afferent Neuron ◽  
Afferent Neurons ◽  
Vagal Afferent ◽  
Fos Expression ◽  
Novel Target ◽  
Anorexigenic Effect

Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca2+ concentration ([Ca2+]i) in single vagal afferent neurons. The Oxt-induced [Ca2+]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca2+]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity.

Leptin and CCK modulate complementary background conductances to depolarize cultured nodose neurons

2006 ◽  
Vol 290 (2) ◽  
pp. C427-C432 ◽  
Author(s):  
J. H. Peters ◽  
R. C. Ritter ◽  
S. M. Simasko
Keyword(s):  
Food Intake ◽  
Outward Current ◽  
Vagal Afferents ◽  
Afferent Neurons ◽  
Inward Current ◽  
Adult Rat ◽  
Nodose Ganglia ◽  
Sodium Dependent ◽  
Ionic Mechanisms ◽  
Vagal Afferent

We have previously reported that intraceliac infusion of leptin induces a reduction of meal size that depends on intact vagal afferents. This effect of leptin is enhanced in the presence of cholecystokinin (CCK). The mechanisms by which leptin and CCK activate vagal afferent neurons are not known. In the present study, we have begun to address this question by using patch-clamp electrophysiological techniques to examine the mechanisms by which leptin and CCK activate cultured vagal afferents from adult rat nodose ganglia. We found that leptin depolarized 41 (60%) of 68 neurons. The magnitude of membrane depolarization was dependent on leptin concentration and occurred in both capsaicin-sensitive and capsaicin-insensitive neurons. We also found that a majority (16 of 22; 73%) of nodose neurons activated by leptin were also sensitive to CCK. CCK-induced depolarization was primarily associated with the increase of an inward current (11 of 12), whereas leptin induced multiple changes in background conductances through a decrease in an outward current (7 of 13), an increase in an inward current (3 of 13), or both (3 of 13). However, further isolation of background currents by recording in solutions that contained only sodium or only potassium revealed that both leptin and CCK were capable of increasing a sodium-dependent conductance or inhibiting a potassium-dependent conductance. Our results support the hypothesis that vagal afferents are a point of convergence and integration of leptin and CCK signaling for control of food intake and suggest multiple ionic mechanisms by which leptin and CCK activate vagal afferent neurons.

Apolipoprotein A-IV stimulates duodenal vagal afferent activity to inhibit gastric motility via a CCK1 pathway

2004 ◽  
Vol 287 (2) ◽  
pp. R354-R359 ◽  
Author(s):  
J. Glatzle ◽  
N. Darcel ◽  
A. J. Rechs ◽  
T. J. Kalogeris ◽  
P. Tso ◽  
...  
Keyword(s):  
Gastric Motility ◽  
Feedback Inhibition ◽  
Lipid Absorption ◽  
Nerve Terminals ◽  
Afferent Activity ◽  
Apolipoprotein A ◽  
Afferent Fibers ◽  
Vagal Afferent ◽  
Upper Gastrointestinal

Apolipoprotein A-IV (apo A-IV), a peptide expressed by enterocytes in the mammalian small intestine and released in response to long-chain triglyceride absorption, may be involved in the regulation of gastric acid secretion and gastric motility. The specific aim of the present study was to determine the pathway involved in mediating inhibition of gastric motility produced by apo A-IV. Gastric motility was measured manometrically in response to injections of either recombinant purified apo A-IV (200 μg) or apo A-I, the structurally similar intestinal apolipoprotein not regulated by triglyceride absorption, close to the upper gastrointestinal tract in urethane-anesthetized rats. Injection of apo A-IV significantly inhibited gastric motility compared with apo A-I or vehicle injections. The response to exogenous apo A-IV injections was significantly reduced by 77 and 55%, respectively, in rats treated with the CCK1 receptor blocker devazepide or after functional vagal deafferentation by perineural capsaicin treatment. In electrophysiological experiments, isolated proximal duodenal vagal afferent fibers were recorded in vitro in response to close-arterial injection of vehicle, apo A-IV (200 μg), or CCK (10 pmol). Apo A-IV stimulated the discharge of duodenal vagal afferent fibers, significantly increasing the discharge in 4/7 CCK-responsive units, and the response was abolished by CCK1 receptor blockade with devazepide. These data suggest that apo A-IV released from the intestinal mucosa during lipid absorption stimulates the release of endogenous CCK that activates CCK1 receptors on vagal afferent nerve terminals initiating feedback inhibition of gastric motility.

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