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Helen E Raybould - One of the best experts on this subject based on the ideXlab platform.

  • microbial metabolites and the vagal Afferent Pathway in the control of food intake
    Physiology & Behavior, 2021
    Co-Authors: Helen E Raybould, Danielle L Zumpano
    Abstract:

    The gut microbiota is able to influence overall energy balance via effects on both energy intake and expenditure, and is a peripheral target for potential obesity therapies. However, the precise mechanism by which the gut microbiota influences energy intake and body weight regulation is not clear. Microbes use small molecules to communicate with each other; some of these molecules are ligands at mammalian receptors and this may be a mechanism by which microbes communicate with the host. Here we briefly review the literature showing beneficial effects of microbial metabolites on food intake regulation and examine the potential role for vagal Afferent neurons, the gut-brain axis.

  • human milk oligosaccharide 2 fucosyllactose supplementation improves gut barrier function and signaling in the vagal Afferent Pathway in mice
    Food & Function, 2021
    Co-Authors: Sunhye Lee, Michael L Goodson, Wendie Vang, Jennifer M Rutkowsky, Karen M Kalanetra, Mrittika Bhattacharya, Daniela Barile, Helen E Raybould
    Abstract:

    2'-Fucosyllactose (2'-FL) is one of the predominant oligosaccharides found in human milk and has several well-established beneficial effects in the host. It has previously been shown that 2'-FL can improve the metabolic phenotype in high-fat (HF)-fed mice. Here we investigated whether dietary supplementation with 2'-FL was associated with improved intestinal barrier integrity, signaling in the vagal Afferent Pathway and cognitive function. Mice were fed either a low-fat (LF, 10% fat per kcal) or HF (45% fat per kcal) diet with or without supplementation of 2'-FL (10% w/w) in the diet for 8 weeks. Body weight, energy intake, fat and lean mass, intestinal permeability (ex vivo in Ussing chambers), lipid profiles, gut microbiome and microbial metabolites, and cognitive functions were measured. Vagal Afferent activity was measured via immunohistochemical detection of c-Fos protein in the brainstem in response to peripheral administration of cholecystokinin (CCK). 2'-FL significantly attenuated the HF-induced increase in fat mass and energy intake. 2'-FL significantly reduced intestinal permeability and significantly increased expression of interleukin (IL)-22, a cytokine known for its protective role in the intestine. Additionally, 2'-FL led to changes in the gut microbiota composition and in the associated microbial metabolites. Signaling in the vagal Afferent Pathway was improved but there was no effect on cognitive function. In conclusion, 2'-FL supplementation improved the metabolic profiles, gut barrier integrity, lipid metabolism and signaling in the vagal Afferent Pathway. These findings support the utility of 2'-FL in the control of gut barrier function and metabolic homeostasis under a metabolic challenge.

  • Glucagon-Like Peptide 1 Interacts with Ghrelin and Leptin to Regulate Glucose Metabolism and Food Intake through Vagal Afferent Neuron Signaling
    Journal of Nutrition, 2015
    Co-Authors: Charlotte C. Ronveaux, Daniel Tomé, Helen E Raybould
    Abstract:

    Emerging evidence has suggested a possible physiologic role for peripheral glucagon-like peptide 1 (GLP-1) in regulating glucose metabolism and food intake. The likely site of action of GLP-1 is on vagal Afferent neurons (VANs). The vagal Afferent Pathway is the major neural Pathway by which information about ingested nutrients reaches the central nervous system and influences feeding behavior. Peripheral GLP-1 acts on VANs to inhibit food intake. The mechanism of the GLP-1 receptor (GLP-1R) is unlike other gut-derived receptors; GLP-1Rs change their cellular localization according to feeding status rather than their protein concentrations. It is possible that several gut peptides are involved in mediating GLP-1R translocation. The mechanism of peripheral GLP-1R translocation still needs to be elucidated. We review data supporting the role of peripheral GLP-1 acting on VANs in influencing glucose homeostasis and feeding behavior. We highlight evidence demonstrating that GLP-1 interacts with ghrelin and leptin to induce satiation. Our aim was to understand the mechanism of peripheral GLP-1 in the development of noninvasive antiobesity treatments.

  • deletion of leptin signaling in vagal Afferent neurons results in hyperphagia and obesity
    Molecular metabolism, 2014
    Co-Authors: Guillaume De Lartigue, Charlotte C. Ronveaux, Helen E Raybould
    Abstract:

    The vagal Afferent Pathway senses hormones released from the gut in response to nutritional cues and relays these signals to the brain. We tested the hypothesis that leptin resistance in vagal Afferent neurons (VAN) is responsible for the onset of hyperphagia by developing a novel conditional knockout mouse to delete leptin receptor selectively in sensory neurons (Nav1.8/LepR fl/fl mice). Chow fed Nav1.8/LepR fl/fl mice weighed significantly more and had increased adiposity compared with wildtype mice. Cumulative food intake, meal size, and meal duration in the dark phase were increased in Nav1.8/LepR fl/fl mice; energy expenditure was unaltered. Reduced satiation in Nav1.8/LepR fl/fl mice is in part due to reduced sensitivity of VAN to CCK and the subsequent loss of VAN plasticity. Crucially Nav1.8/LepR l/fl mice did not gain further weight in response to a high fat diet. We conclude that disruption of leptin signaling in VAN is sufficient and necessary to promote hyperphagia and obesity.

  • vagal Afferent neurons in high fat diet induced obesity intestinal microflora gut inflammation and cholecystokinin
    Physiology & Behavior, 2011
    Co-Authors: Guillaume De Lartigue, Claire B De La Serre, Helen E Raybould
    Abstract:

    The vagal Afferent Pathway is the major neural Pathway by which information about ingested nutrients reaches the CNS and influences both GI function and feeding behavior. Vagal Afferent neurons (VAN) express receptors for many of the regulatory peptides and molecules released from the intestinal wall, pancreas, and adipocytes that influence GI function, glucose homeostasis, and regulate food intake and body weight. As such, they play a critical role in both physiology and pathophysiology, such as obesity, where there is evidence that vagal Afferent function is altered. This review will summarize recent findings on changes in vagal Afferent function in response to ingestion of high fat diets and explore the hypothesis that changes in gut microbiota and integrity of the epithelium may not only be important in inducing these changes but may be the initial events that lead to dysregulation of food intake and body weight in response to high fat, high energy diets.

Chung Owyang - One of the best experts on this subject based on the ideXlab platform.

  • Octreotide reduces perception of rectal electrical stimulation by spinal Afferent Pathway inhibition
    American Journal of Physiology-Gastrointestinal and Liver Physiology, 1995
    Co-Authors: William D. Chey, Ahmad Beydoun, D. J. Roberts, William L. Hasler, Chung Owyang
    Abstract:

    Octreotide reduces perception of rectal distension in normal volunteers and irritable bowel patients. To localize octreotide's site of action, perceptual and evoked potential responses to rectal electrical stimulation were tested in seven normal volunteers after double-blind octreotide (100 micrograms 2) or placebo. After octreotide, the currents needed to elicit threshold perception of square-wave impulses delivered to the rectum were 29% higher than after placebo. When electrical stimulation was delivered at constant currents 50% above threshold, rectal perception scores were significantly reduced after octreotide compared with placebo. Rectal electrical stimulation led to characteristic and reproducible cerebral evoked potentials. Octreotide had no effect on latencies, but reduced peak-to-peak amplitudes by 35% compared with placebo. Rectal electrical stimulation also led to characteristic and reproducible spinal evoked potentials. Octreotide had no effect on spinal latencies, but reduced peak-to-peak amplitudes by 51%. In conclusion, octreotide reduces perception of rectal electrical stimulation, which is associated with inhibition of cerebral and spinal evoked potential amplitude, indicating effects on spinal Afferent Pathways.

  • secretin at physiological doses inhibits gastric motility via a vagal Afferent Pathway
    American Journal of Physiology-gastrointestinal and Liver Physiology, 1995
    Co-Authors: Chung Owyang
    Abstract:

    Secretin is an important modulator of gastric motility. In this study, we investigated the site(s) and mechanism(s) of action of secretin to inhibit gastric motility, using an in vivo rat model. Intragastric pressure response to graded doses of secretin was recorded in anesthetized rats by a balloon attached to a catheter passed through an incision in the duodenum into the body of the stomach. The intragastric pressure was set at 10 cmH2O with balloon distension. Intravenous infusion of secretin (1.4, 2.8, 5.6, 11.2, and 22.4 pmol.kg-1.h-1) decreased intragastric pressure in a dose-dependent manner. The threshold dose was 2.8 pmol.kg-1.h-1, and the effective dose at 50% (ED50) was 5.6 pmol.kg-1.h-1, which produced physiological levels of plasma secretin. Pretreatment with hexamethonium (10 mg/kg) markedly reduced gastric motor response to secretin (5.6 pmol.kg-1.h-1). Bilateral truncal vagotomy also significantly diminished gastric motor responses to secretin. In contrast, secretin (5.6 pmol.kg-1.h-1) had no effect on gastric contraction evoked by electrical vagal stimulation (1.25-5 Hz) or carbachol (10(-6) to 3 x 10(-5) M). These observations indicate that physiological concentrations of secretin act via stimulation of presynaptic cholinergic neurons in a vagally mediated Pathway. In subsequent studies, we demonstrated that perivagal treatment 4 days before with the sensory neurotoxin, capsaicin, abolished gastric motor response to secretin but did not affect contraction evoked by electrical vagal stimulation. Similarly, we also showed that gastroduodenal application of capsaicin for 30 min also markedly reduced gastric response to secretin. These observations indicate that physiological doses of secretin act on vagal Afferent Pathways originating from the gastroduodenal mucosa to induce gastric relaxation.

  • endogenous cholecystokinin stimulates pancreatic enzyme secretion via vagal Afferent Pathway in rats
    Gastroenterology, 1994
    Co-Authors: Chung Owyang
    Abstract:

    Abstract Background/Aims: Recently we showed that doses of Cholecystokinin octapeptide (CCK-8) that produce physiological plasma CCK levels act via stimulation of Afferent vagal Pathway to mediate pancreatic enzyme secretion. In this study we investigated if endogenous CCK also acts via similar Pathway. Methods: In anesthetized rats, plasma CCK levels were elevated by diversion of bile pancreatic juice and duodenal casein feeding. The effects of acute vagotomy as well as that of chemical ablation of the Afferent vagal Pathway on pancreatic enzyme secretion evoked by increased endogenous plasma CCK levels were investigated. Results: Diversion of bile pancreatic juice elevated plasma CCK levels from a basal level of 0.6 ± 0.1 pmol/L to 8.9 ± 2.1 pmol/L and caused a more than twofold increase in pancreatic protein secretion. Similar increases in plasma CCK levels and pancreatic secretion were observed with duodenal administration of casein. Vagotomy or perivagal application of capsaicin, a sensory neurotoxin, abolished increases in pancreatic secretion but not plasma CCK levels in response to diversion of bile pancreatic secretion or duodenal administration of casein. In contrast, pancreatic protein responses to 2-deoxy-d-glucose, a central vagal stimulant, remained intact in rats with perivagal capsaicin treatment indicating capsaicin did not affect efferent vagal function. Conclusions: Endogenous CCK under physiological conditions acts via stimulation of vagal Afferent Pathway to mediate pancreatic enzyme secretion.

  • vagal Afferent Pathway mediates physiological action of cholecystokinin on pancreatic enzyme secretion
    Journal of Clinical Investigation, 1993
    Co-Authors: Chung Owyang
    Abstract:

    To establish the mechanism(s) and site(s) of action of cholecystokinin (CCK) on pancreatic secretion under physiological conditions, we used an in vivo model using anesthetized rats with pancreaticobiliary cannulas. Infusion of CCK-8 (10-160 pmol/kg per h) produced a dose-dependent increase in plasma CCK levels. CCK-8 infusion at 40 pmol/kg per h produced a plasma CCK level of 7.9 +/- 1.5 pM and an 80% increase in pancreatic protein output over basal. This level was closely approximated by a postprandial peak plasma CCK level by 6.2 +/- 1.1 pM. Pretreatment with atropine or hexamethonium completely abolished pancreatic protein response to low doses of CCK-8 (10-40 pmol/kg per h) but had only partial effect on doses > 40 pmol/kg per h. Bilateral vagotomy also abolished the pancreatic responses to low doses of CCK-8. Similarly perivagal treatment with a sensory neurotoxin, capsaicin, caused a complete inhibition of pancreatic protein secretion in response to CCK-8 infusion. In contrast, pancreatic protein responses to bethanechol were similar in control and capsaicin-treated rats. In separate studies we demonstrated that gastroduodenal but not jejunal application of capsaicin for 30 min abolished pancreatic protein secretion in response to physiological doses of CCK-8. In conclusion, CCK at physiological levels stimulates pancreatic enzyme secretion via a capsaicin-sensitive Afferent vagal Pathway originating from the gastroduodenal mucosa.

Helge Holzer - One of the best experts on this subject based on the ideXlab platform.

  • intestinal lipid inhibits gastric emptying via cck and a vagal capsaicin sensitive Afferent Pathway in rats
    American Journal of Physiology-gastrointestinal and Liver Physiology, 1994
    Co-Authors: Helge Holzer, C M Turkelson, Travis E Solomon, Helen E Raybould
    Abstract:

    The mechanism by which lipid in the duodenum inhibits gastric emptying was investigated in awake rats fitted with chronic gastric and duodenal cannulas. Perfusion of the duodenum with lipid (Intralipid, 5 and 10%; total amount 50 and 100 mg) caused a significant inhibition (26 and 78%, respectively) of gastric emptying of a nonnutrient liquid (0.9% saline). Functional ablation of the capsaicin-sensitive vagal, but not the spinal, sensory innervation to the upper gastrointestinal tract significantly attenuated by 57% lipid-induced inhibition of gastric emptying. In intact rats, administration of a specific cholecystokinin (CCK)-A receptor antagonist, devazepide, significantly attenuated by 66% the response to lipid. Administration of devazepide in perivagal capsaicin-treated rats did not further reduce the response to lipid. These results suggest that lipid in the duodenum inhibits gastric emptying via a mechanism involving an action of CCK at type A receptors and capsaicin-sensitive vagal Afferents.

  • secretin inhibits gastric emptying in rats via a capsaicin sensitive vagal Afferent Pathway
    European Journal of Pharmacology, 1993
    Co-Authors: Helen E Raybould, Helge Holzer
    Abstract:

    In awake rats, fitted with chronic gastric fistulas, secretin (30 and 300 pmol intraperitoneal, i.p.) inhibited gastric emptying of a non-nutrient liquid by 16% (NS) and 38% (P < 0.01) respectively. Functional ablation of vagal, but not spinal, capsaicin-sensitive Afferents reversed the action of secretin by 61%. Inhibition of gastric emptying induced by cholecystokinin (CCK) (30 pmol i.p.) was reversed by around 50% by ablation of either the vagal or spinal capsaicin-sensitive Afferent Pathway. These results suggest that hormones released after a meal can inhibit gastric emptying via activation of visceral Afferent Pathways.

Yan Feng - One of the best experts on this subject based on the ideXlab platform.

  • the baroreflex Afferent Pathway plays a critical role in h2s mediated autonomic control of blood pressure regulation under physiological and hypertensive conditions
    Acta Pharmacologica Sinica, 2021
    Co-Authors: Yan Feng, Li Liu, Xun Sun, Rongrong Zha, Hongdan Wang, Mengdi Zhang
    Abstract:

    Hydrogen sulfide (H2S), which is closely related to various cardiovascular disorders, lowers blood pressure (BP), but whether this action is mediated via the modification of baroreflex Afferent function has not been elucidated. Therefore, the current study aimed to investigate the role of the baroreflex Afferent Pathway in H2S-mediated autonomic control of BP regulation. The results showed that baroreflex sensitivity (BRS) was increased by acute intravenous NaHS (a H2S donor) administration to renovascular hypertensive (RVH) and control rats. Molecular expression data also showed that the expression levels of critical enzymes related to H2S were aberrantly downregulated in the nodose ganglion (NG) and nucleus tractus solitarius (NTS) in RVH rats. A clear reduction in BP by the microinjection of NaHS or L-cysteine into the NG was confirmed in both RVH and control rats, and a less dramatic effect was observed in model rats. Furthermore, the beneficial effects of NaHS administered by chronic intraperitoneal infusion on dysregulated systolic blood pressure (SBP), cardiac parameters, and BRS were verified in RVH rats. Moreover, the increase in BRS was attributed to activation and upregulation of the ATP-sensitive potassium (KATP) channels Kir6.2 and SUR1, which are functionally expressed in the NG and NTS. In summary, H2S plays a crucial role in the autonomic control of BP regulation by improving baroreflex Afferent function due at least in part to increased KATP channel expression in the baroreflex Afferent Pathway under physiological and hypertensive conditions.

  • contribution of baroreflex Afferent Pathway to npy mediated regulation of blood pressure in rats
    Neuroscience Bulletin, 2020
    Co-Authors: Yan Feng, Luqi Wang, Jie Sun, Yang Liu, S Y Zhao, Qiuxin Yan, Zhuo Liu, Xun Sun
    Abstract:

    Neuropeptide Y (NPY), a metabolism-related cardiovascular factor, plays a crucial role in blood pressure (BP) regulation via peripheral and central Pathways. The expression of NPY receptors (Y1R/Y2R) specific to baroreflex Afferents impacts on the sexually dimorphic neural control of circulation. This study was designed to investigate the expression profiles of NPY receptors in the nodose ganglion (NG) and nucleus tractus solitary (NTS) under hypertensive conditions. To this end, rats with hypertension induced by NG-nitro-L-arginine methylester (L-NAME) or high fructose drinking (HFD), and spontaneously hypertensive rats (SHRs) were used to explore the effects/mechanisms of NPY on BP using functional, molecular, and electrophysiological approaches. The data showed that BP was elevated along with baroreceptor sensitivity dysfunction in model rats; Y1R was up- or down-regulated in the NG or NTS of male and female HFD/L-NAME groups, while Y2R was only down-regulated in the HFD groups as well as in the NG of the male L-NAME group. In SHRs, Y1R and Y2R were both down-regulated in the NTS, and not in the NG. In addition to NPY-mediated energy homeostasis, leptin-melanocortin activation may be essential for metabolic disturbance-related hypertension. We found that leptin and α-melanocyte stimulating hormone (α-MSH) receptors were aberrantly down-regulated in HFD rats. In addition, α-MSH concentrations were reduced and NPY concentrations were elevated in the serum and NTS at 60 and 90 min after acute leptin infusion. Electrophysiological recordings showed that the decay time-constant and area under the curve of excitatory post-synaptic currents were decreased by Y1R activation in A-types, whereas, both were increased by Y2R activation in Ah- or C-types. These results demonstrate that sex- and Afferent-specific NPY receptor expression in the baroreflex Afferent Pathway is likely to be a novel target for the clinical management of metabolism-related and essential hypertension.

  • direct activation of tachykinin receptors within baroreflex Afferent Pathway and neurocontrol of blood pressure regulation
    CNS Neuroscience & Therapeutics, 2019
    Co-Authors: Mei Yuan, M N, Tingyu Wang, Yan Feng, Pei Chen, Sijie Liu, Yunxia Guo, Yue Wang, Yao Fan, Luqi Wang
    Abstract:

    Aim Substance P (SP) causes vasodilation and blood pressure (BP) reduction. However, the involvement of tachykinin receptors (NKRs) within baroreflex Afferent Pathway in SP-mediated BP regulation is largely unknown. Methods Under control and hypertensive condition, NKRs' expressions were evaluated in nodose (NG) and nucleus of tractus solitary (NTS) of male, female, and ovariectomized (OVX) rats; BP was recorded after microinjection of SP and NKRs agonists into NG; Baroreceptor sensitivity (BRS) was tested as well. Results Immunostaining and immunoblotting data showed that NK1R and NK2R were estrogen-dependently expressed on myelinated and unmyelinated Afferents in NG. A functional study showed that BP was reduced dose-dependently by SP microinjection, which was more dramatic in males and can be mimicked by NK1R and NK2R agonists. Notably, further BP elevation and BRS dysfunction were confirmed in desoxycorticosterone acetate (DOCA)-salt model in OVX compared with DOCA-salt model in intact female rats. Additionally, similar changes in NKRs' expression in NG were also detected using DOCA-salt and SHR. Compared with NG, inversed expression profiles of NKRs were also found in NTS with either gender. Conclusion The estrogen-dependent NKRs' expression in baroreflex Afferent Pathway participates at least partially in sexual-dimorphic and SP-mediated BP regulation under physiological and hypertensive conditions.

Takashi Higuchi - One of the best experts on this subject based on the ideXlab platform.

  • Prolactin releasing peptides modulate background firing rate and milk-ejection related burst of oxytocin cells in the supraoptic nucleus.
    Brain research bulletin, 2004
    Co-Authors: Kazumasa Honda, Kazumi Narita, Takuya Murata, Takashi Higuchi
    Abstract:

    The hypothalamic dorsomedial nucleus is suggested to be a final relay site for the Afferent Pathway of milk-ejection reflex. Existence of prolactin releasing peptide-immunoreactive cells in the dorsomedial nucleus and synaptic contact of prolactin releasing peptide-immunoreactive terminals with oxytocin cells was reported. Experiments were done to test the effect of prolactin releasing peptide on the electrical activity of oxytocin cells in the supraoptic nucleus. In rat brain slice preparations, oxytocin cells were unresponsive to the peptide. In lactating rats, although lateral ventricular injection of prolactin releasing peptide (20 nmol) was ineffective, a hundred nanomoles of the peptide increased basal activity and amplitude of milk-ejection related burst firing of oxytocin cells. Cells responded to lateral ventricular injection of peptides were unresponsive to direct application of peptides by pressure ejection from the recording electrode. These results suggest that prolactin releasing peptide may modulate electrical activity of oxytocin cells not through its direct action on oxytocin cells but through its action on area other than supraoptic nucleus.

  • Lesion and electrophysiological studies on the hypothalamic Afferent Pathway of the milk ejection reflex in the rat.
    Neuroscience, 1992
    Co-Authors: S. Takano, Hideo Negoro, K. Honda, Takashi Higuchi
    Abstract:

    Abstract The Afferent Pathway of the milk ejection reflex in the hypothalamus was investigated with lesion and electrophysiological methods in anesthetized lactating rats. Destruction of the central region of the mid-hypothalamus (n = 12) blocked milk ejections induced by suckling, while that of the lateral region (n = 7) had no effect. In an electrophysiological study, extracellular recordings of neurons antidromically activated by electrical stimulation of the supraoptic nucleus were obtained from the ipsilateral hypothalamus caudal to the paraventricular nucleus (n = 84). Thirty-nine neurons were examined to see whether their firing activities changed during the milk ejection reflex. A group of 13 neurons were found to show changes in their activities prior to the reflex milk ejection; the neurons displayed a brief high-frequency burst of spikes before each milk ejection in the same manner as oxytocin neurons, and none of them antidromically responded to electrical stimulation of the neurohypophysis. The bursting neurons were recorded from the dorsomedial hypothalamic nucleus (n = 6), the region just lateral to that nucleus (n = 3) and the posterior hypothalamus (n = 4). The locations were included in a region whose destruction blocked the milk ejection reflex. These results indicate that the Afferent Pathway of the milk ejection reflex in the rat runs through the medial portion of the hypothalamus posterior to the paraventricular nucleus and that this region contains neurons which relay the input to the oxytocin neurons projecting in the neurohypophysis.