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ABSTRACT: Peripheral and central glucose sensing play a major role in the regulation of food intake. Peripheral sensing occurs at duodenal and portal levels, although the importance of these sensing sites is still controversial. The present study aimed to compare the respective influence of these sensing pathways on the eating patterns; plasma concentrations of glucose, insulin and glucagon-like peptide-1 (GLP-1); and brain activity in juvenile pigs. In Experiment 1, we characterised the changes in the microstructure as a result of a 30-min meal in eight conscious animals after duodenal or portal glucose infusion in comparison with saline infusion. In Experiment 2, glucose, insulin and GLP-1 plasma concentrations were measured during 2 h after duodenal or portal glucose infusions in four anaesthetised animals. In Experiment 3, single photon emission computed tomography brain imaging was performed in five anaesthetised animals receiving duodenal or portal glucose or saline infusions. Both duodenal and portal glucose decreased the amount of food consumed, as well as the ingestion speed, although this effect appeared earlier with the portal infusion. Significant differences of glucose and GLP-1 plasma concentrations between treatments were found at the moment of brain imaging. Both duodenal and portal glucose infusions activated the dorsolateral prefrontal cortex and primary somatosensory cortex. Only duodenal glucose infusion was able to induce activation of the prepyriform area, orbitofrontal cortex, caudate and putamen, as well as deactivation of the anterior prefrontal cortex and anterior entorhinal cortex, whereas only portal glucose infusion induced a significant activation of the insular cortex. We demonstrated that duodenal and portal glucose infusions led to the modulation of brain areas that are known to regulate eating behaviour, which probably explains the decrease of food intake after both stimulations. These stimulation pathways induced specific systemic and central responses, suggesting that different brain processing matrices are involved.
Journal of Neuroendocrinology 04/2012; 24(8):1096-105. · 3.14 Impact Factor
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ABSTRACT: This study investigated the behavioural and brain responses towards conditioned flavours with different hedonic values in juvenile pigs. Twelve 30-kg pigs were given four three-day conditioning sessions: they received three different flavoured meals paired with intraduodenal (i.d.) infusions of 15% glucose (F(Glu)), lithium chloride (F(LiCl)), or saline (control treatment, F(NaCl)). One and five weeks later, the animals were subjected to three two-choice feeding tests without reinforcement to check the acquisition of a conditioned flavour preference or aversion. In between, the anaesthetised pigs were subjected to three (18)FDG PET brain imaging coupled with an olfactogustatory stimulation with the conditioned flavours. During conditioning, the pigs spent more time lying inactive, and investigated their environment less after the F(LiCl) than the F(NaCl) or F(Glu) meals. During the two-choice tests performed one and five weeks later, the F(NaCl) and F(Glu) foods were significantly preferred over the F(LICl) food even in the absence of i.d. infusions. Surprisingly, the F(NaCl) food was also preferred over the F(Glu) food during the first test only, suggesting that, while LiCl i.d. infusions led to a strong flavour aversion, glucose infusions failed to induce flavour preference. As for brain imaging results, exposure to aversive or less preferred flavours triggered global deactivation of the prefrontal cortex, specific activation of the posterior cingulate cortex, as well as asymmetric brain responses in the basal nuclei and the temporal gyrus. In conclusion, postingestive visceral stimuli can modulate the flavour/food hedonism and further feeding choices. Exposure to flavours with different hedonic values induced metabolism differences in neural circuits known to be involved in humans in the characterization of food palatability, feeding motivation, reward expectation, and more generally in the regulation of food intake.
PLoS ONE 01/2012; 7(5):e37968. · 4.09 Impact Factor
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ABSTRACT: Compared to lean subjects, obese men have less activation in the dorsolateral prefrontal cortex, a brain area implicated in the inhibition of inappropriate behavior, satiety, and meal termination. Whether this deficit precedes weight gain or is an acquired feature of obesity remains unknown. An adult animal model of obesity may provide insight to this question since brain imaging can be performed in lean vs. obese conditions in a controlled study. Seven diet-induced obese adult minipigs were compared to nine lean adult minipigs housed in the same conditions. Brain activation after an overnight fasting was mapped in lean and obese subjects by single photon emission computed tomography. Cerebral blood flow, a marker of brain activity, was measured in isoflurane-anesthetized animals after the intravenous injection of 99mTc-HMPAO (750 MBq). Statistical analysis was performed using statistical parametric mapping (SPM) software and cerebral blood flow differences were determined using co-registered T1 magnetic resonance imaging (MRI) and histological atlases. Deactivations were observed in the dorsolateral and anterior prefrontal cortices in obese compared to lean subjects. They were also observed in several other structures, including the ventral tegmental area, the nucleus accumbens, and nucleus pontis. On the contrary, activations were found in four different regions, including the ventral posterior nucleus of the thalamus and middle temporal gyrus. Moreover, the anterior and dorsolateral prefrontal cortices as well as the insular cortex activity was negatively associated with the body weight. We suggested that the reduced activation of prefrontal cortex observed in obese humans is probably an acquired feature of obesity since it is also found in minipigs with a diet-induced obesity.
Obesity 01/2011; 19(4):749-56. · 4.28 Impact Factor
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ABSTRACT: We used high-magnetic field (4.7 T) magnetic resonance imaging (MRI) to build the first high-resolution (100 microm x 150 microm x 100 microm) three-dimensional (3D) digital atlas in stereotaxic coordinates of the brain of a female domestic pig (Sus scrofa domesticus). This atlas was constructed from one hemisphere which underwent a symmetrical transformation through the midsagittal plane. Concomitant construction of a 3D histological atlas based on the same scheme facilitated control of deep brain structure delimitation and enabled cortical mapping to be achieved. The atlas contains 178 individual cerebral structures including 42 paired and 9 single deep brain structures, 5 ventricular system areas, 6 paired deep cerebellar nuclei, 12 cerebellar lobules and 28 cortical areas per hemisphere. Given the increasing importance of pig brains in medical research, this atlas should be a useful tool for intersubject normalization in anatomical imaging as well as for precisely localizing brain areas in functional MR studies or electrode implantation trials. The atlas can be freely downloaded from our institution's Website.
Journal of neuroscience methods 09/2010; 192(1):102-9. · 2.30 Impact Factor
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ABSTRACT: The vagal motor system is involved in the regulation of cardiorespiratory and gastrointestinal functions. Vagal motor neurons are localized near or adjacent to catecholaminergic neurons, but their co-localisation seems species dependent, present in the cat but absent in the rabbit. In pig, a species commonly used as an experimental model in humans brain disorders (sudden infant death syndrome, hypoxia), the relationship is poorly understood. We aimed at describing the distribution of vagal motor neurons and tyrosine hydroxylase-immunoreactive (-ir) neurons by using a double staining method in combination with retrograde tracing of vagal efferent neurons. After fluorogold impregnation of the central part of the sectioned left cervical vagal trunk, two main vagal motor neuronal populations were located in the dorsal motor nucleus of the vagus nerve (DMX) and in the area of the nucleus ambiguus (Amb). Like in the human, the DMX was composed of different subpopulations of neurons with the same morphological characteristics. Immunohistochemistry of catecholaminergic synthesizing enzymes differentiated two main sites containing vagal motor populations: the dorsomedial and the ventrolateral medulla. TH-ir was rarely seen in vagal motor neurons of the DMX, but TH-ir neurons were present around the two main vagal motor neuronal populations that contained TH-ir fibres. The anatomical organisation of the vagal motor and the catecholaminergic neuronal systems are similar to those described in humans and suggest that the involvement of the catecholamines in the control of the vagal motor system may be similar in pigs and in humans.
Journal of chemical neuroanatomy 08/2009; 38(4):257-65. · 1.75 Impact Factor
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ABSTRACT: La stimulation vagale chronique (VNS), une thérapeutiq ue de l'épilepsie pharmacorésistante, serait capable chez l'animal et chez l'homme de modifier le comportement alimentaire. Le but de notre étude était de préciser l'impact de la VNS sur le comportement alimentaire du porc pris comme modèle de l'homme et d'étudier l'origine de ses e ffets potentiels. La VNS conduit au bout de cinq semaines à une réduction de la quantité d'aliment ingéré. Cette réduction n'est pas la conséquence de la stimulation des e fférences vagales, la compliance ou l'évacuation de l'estomac, n'étant pas modifiée. Par contre, la VNS provoque une réorganisation de l'activation cérébrale mettant vraisemblablement en jeu les structures sous-corticales impliquées dans le processus de récompense. L'activation du bulbe olfactif au cours de la VNS est probablement l'un des éléments à l'origine des modifications drastiques des préférences alimentaires en faveur des lipides. Chronic vagus nerve stimulation (VNS), used to treat refractory epilepsy, has the potential to alter food intake in animals and humans. The aim of our study was to evaluate the impact of VNS on the feeding behaviour of pigs used as a human model, and to investigate the origin of its potential effects. Food intake was significantly decreased after five weeks of chronic VNS. This reduction was not due to stimulation of the vagus efferents as neither gastric compliance nor gastric emptying was altered. VNS triggered a reorganisation of brain activation, probably via subcortical structures involved in the reward mechanism. The activation of the olfactory bulb during VNS is probably one of the mechanisms responsible for the drastic changes in food preference in favour of lipids.
Bulletin de l'Académie vétérinaire de France 01/2008; 161(5):441-448. · 0.09 Impact Factor
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ABSTRACT: Selective neuronal NOS (nNOS) inhibitors have been developed for possible application in cerebral ischemia and neurodegenerative disorders. To investigate the degree of interference with peripheral nNOS, the influence of the selective nNOS inhibitor ARL 17477 was studied on electrically induced nitrergic relaxations in pig gastric fundus strips and on gastric fundic compliance in conscious pig. Circular muscle strips of porcine gastric fundus were electrically stimulated (10 s trains at 4 Hz, 0.1 ms and 40 V). ARL 17477 inhibited the electrically induced relaxations in a concentration-dependent way (3x10(-6) M-10(-4) M). The inhibitory effect of ARL 17477 developed more progressively than that of N(G)-nitro-L-arginine methyl ester (L-NAME; 3x10(-4) M). In conscious pigs, instrumented with a fundic cannula, L-NAME (20 mg/kg i.v.) significantly increased mean arterial blood pressure and decreased fundic compliance in the fasted state (71+/-13 ml/mm Hg versus 185+/-37 ml/mm Hg after saline; P<0.05). ARL 17477 (3 mg/kg, i.v.) did not influence blood pressure but influenced gastric fundic volume-pressure curves in a similar way as L-NAME. Plasma concentration analysis of ARL 17477 indicated a half-life of less than 30 min in pig. ARL 17477 thus inhibits the effect of nitrergic neurons in the pig gastric fundus in vitro, leading to inhibited gastric compliance in the conscious pig. The study indicates that selective nNOS inhibitors, applied for cerebral disorders, might also interfere with neuronal nitrergic regulation of gastrointestinal motility.
European Journal of Pharmacology 12/2005; 525(1-3):143-9. · 2.52 Impact Factor
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ABSTRACT: Hyperglycemia markedly modifies gastro-duodenal motility. The question was raised whether hyperinsulinaemia, which is usually concomitant to hyperglycemia, could be the factor responsible for this effect through alteration of gastro-duodenal sensitivity. Indeed, vagal receptors are directly activated by insulin in lambs. However, insulin action significantly differs in ruminants and non-ruminants. The aim of our study was therefore to check (i) if insulin per se was able to modulate basal and distension induced discharges of duodenal vagal afferents in a monogatric animal model and (ii) if its action was direct or indirect through changes in gut compliance. Fourteen duodenal mechanoreceptors were studied in anaesthetized curarized pigs using the "single-fiber" method performed on the left cervical vagus. The characteristics of the vagal receptors were studied before (Control), and after (i) local insulin infusion in the gastroepiploic artery (IA), (ii) IV insulin perfusion inducing systemic hypoglycemia (IV), and (iii) during an euglycemic hyperinsulinemic clamp (EH). Basal recording, isobaric and isovolumetric distensions were performed in all experimental conditions. Basal discharge was significantly increased during IA (5.8+/-0.28 spikes/5 s), IV (6.6+/-0.30 spikes/5 s) and EH (5.7+/-0.25 spikes/5 s) compared to Control (4.4+/-0.27 spikes/5 s, p<0.05). Responses during isobaric and isovolumetric distensions were identical irrespective of the experimental condition. Gut compliance and intraluminal pressure during basal recording were not modified (p>0.05). In conclusion, insulin increased duodenal vagal mechanoreceptors basal activity but did not modulate the mechanosensitivity of the vagal units. Insulin-induced increase in basal discharge rate was due to hyperinsulinemia per se since it persisted during the euglycemic hyperinsulinemic clamp.
Autonomic Neuroscience 10/2005; 122(1-2):29-37. · 1.86 Impact Factor
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ABSTRACT: A characteristic dietary feature at weaning is a switch from a milk-based to plant-based diet, i.e. from a non-fibrous to a fibrous diet. The present study aimed to evaluate the effects of such an abrupt dietary switch on gastric emptying rate in pigs maintained on a milk substitute after weaning. Eighteen piglets were kept on a milk substitute for 5 weeks after weaning and were then switched to wheat-based or barley-based diets or kept on the milk substitute (six piglets per group). All piglets were fasted for 1 d before the switch and daily food intake was then increased linearly to reach initial values within 3 d. The gastric emptying rate was measured by gamma-scintigraphy before and after the switch. Corpo-antral peristalsis was also evaluated by the use of high-frequency scintigraphic frames. The gastric emptying rate of the wheat-based diet was accelerated on days 1 to 3 after the switch, but was similar to that in the milk-substitute group thereafter. This acceleration was concomitant with an enhanced frequency of corpo-antral waves on days 2 and 3. Conversely, the gastric emptying rate of the barley-based diet tended to be enhanced on day 2, but was delayed on days 4 and 5, without any change in frequency of corpo-antral waves. We conclude that a switch from a non-fibrous to a fibrous diet alters the gastric emptying rate differently depending on the type of dietary fibre.
British Journal Of Nutrition 01/2005; 92(6):913-20. · 3.01 Impact Factor
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ABSTRACT: The vagus is involved in the cephalic phase of insulin secretion but its role in the meal absorption phase of insulin release remains to be defined. The aim of this study was therefore to evaluate the role of the vagus in the early and the late meal absorption phases of insulin secretion. In six pigs, venous insulin profiles were compared in intact animals, after ventral or dorsal vagal trunk section, and after section of both vagal trunks (truncal vagotomy). Since gastric emptying could be modified by vagotomy, it was recorded concomitantly by gamma scintigraphy. Semi-solid (porridge) and liquid (glucose 10%) meals were tested. Truncal vagotomy significantly increased insulin release compare to intact animals after glucose (63.8%) and porridge (174.4%) meals in the early and the late absorption phases of insulin secretion, respectively. For the glucose meal, this effect could be explained by a vagally mediated change in gastric emptying rate, since insulin concentrations for a similar amount of nutrient propelled to the duodenum were not different in intact and truncal vagotomized animals. In contrast, after the porridge meal, truncal vagotomy was associated with a second, later occurring increase in circulating insulin, which could not be explained by changes in gastric emptying rate. These results demonstrate for the first time an inhibitory role of the vagus in the late meal absorption phase of insulin release.
Autonomic Neuroscience 11/2002; 101(1-2):68-77. · 1.86 Impact Factor
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ABSTRACT: Incidence of diarrhea at weaning in commercial pigs is an important problem, and diet is thought to be a predisposing factor. The aim of this study was to determine the impact of switching from milk-based to cereal-based diets on the morphology and function of the small intestine of piglets using a model of delayed weaning to isolate the influence of the diet from that of environmental and social factors.
Forty-five piglets received a milk-based diet for 5 weeks after weaning. Thirty piglets were then switched from milk-based to wheat- or barley-based diets, mimicking the dietary change that occurs at weaning. The last 15 piglets remained on the milk-based diet. Piglets were killed 4 days after the dietary switch. Jejunal mucosa morphometry and enzyme activities were measured. Ussing chambers were used to measure intestinal permeability to macromolecules, basal electrical properties, glucose absorption, and induced chloride-secretion.
Alkaline phosphatase- and sucrase-specific activities were higher in both groups of cereal-fed piglets than in milk-fed piglets. Dipeptidylpeptidase IV activity was higher in wheat-fed piglets than in the other groups. Na + -dependent glucose absorption was 1.7-fold higher in cereals-fed piglets than in milk-fed piglets. Serotonin-induced and vasoactive intestinal polypeptide-induced chloride secretion was doubled in cereals-fed piglets. Dietary transition did not influence the other parameters.
These results indicate that switching from milk to cereals increased some mucosal enzyme activities, intestinal Na + -dependent glucose absorption, and response to secretagogues. This supports the hypothesis that dietary factors could initiate diarrhea in the presence of other aggravating factors, such as pathogens or environmental stress.
Journal of Pediatric Gastroenterology and Nutrition 03/2002; 34(2):180-7. · 2.30 Impact Factor
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ABSTRACT: Recent evidence indicates that soybean, which is widely used in animal nutrition, could directly alter intestinal ion and nutrient transport. However, the mechanisms involved are still unknown. The aim of the study was to investigate the effect of three differently treated soybean products on the glucose and Cl- transport capacity in porcine small intestine by the Ussing chamber technique. Jejunal and ileal piglet epithelial tissues were pre-incubated with extracts of raw soybean flour (RSF), heated soybean flour (HSF), or ethanol heat-treated soybean protein concentrate (SPC). The Na(+)-dependent glucose co-absorption capacity was then measured as an increase in the short-circuit current (ISC) after luminal addition of D-glucose. The effect of the soybean products on cAMP-dependent Cl- secretion was measured as the increase in ISC after the addition of the phosphodiesterase inhibitor, theophylline, while nervous regulation of Cl- secretion was investigated by the addition of the enteric neurotransmitters; 5-hydroxytryptamine (5-HT), substance P and vasoactive intestinal polypeptide (VIP). Incubation with RSF and HSF induced a 30% decrease of the Na(+)-dependent glucose absorption capacity in the jejunum. The effect was similar for RSF in the ileum. Theophylline-induced secretion was decreased by 30% after incubation with RSF, HSF and SPC but only in the jejunum. 5-HT-, substance P- and VIP-induced secretion were not altered by incubation with soybean extracts except in the HSF-incubated where the substance P-induced secretion was significantly reduced. In conclusion, soybean contains ethanol-sensitive heat-insensitive compounds impairing Na(+)-dependent glucose absorption in the jejunum and ileum, and ethanol- and heat-insensitive compounds causing an acute impairment of cAMP-dependent jejunal secretion.
Reproduction Nutrition Development 43(5):409-18. · 1.90 Impact Factor
