Sylvie Guerin

Changes in Brain Activity After a Diet‐Induced Obesity

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.

Role of vagal innervation on intragastric distribution and emptying of liquid and semisolid meals in conscious pigs.

The role of vagal innervation on emptying patterns and intragastric distributions of liquid and semisolid meals is still controversial. We aimed to record these features after dorsal, ventral and truncal vagotomies, using external gamma scintigraphy in conscious pigs in which the dorsal vagus specifically innervates the proximal stomach. Imaging of the stomach was performed for all experimental situations and before surgery using 99mTc‐labelled glucose and porridge meals. Emptying of liquids was faster after dorsal vagotomy, whereas it was unchanged after ventral and truncal vagotomies (T1/2=57 ± 8.5, 31 ± 14.4, 54 ± 9.1 and 42 ± 14.9 min for intact, dorsal, ventral and truncal vagotomies, respectively). On the other hand, truncal vagotomy significantly reduced the emptying rate of semisolids whereas dorsal and ventral vagotomies had no significant effect (T1/2=96 ± 7.2, 113 ± 8.1, 75 ± 9.9 and 260 ± 56.6 min for intact, dorsal, ventral and truncal vagotomies). Morphological analysis of the gastric shape confirmed an overdistended proximal stomach after truncal vagotomy only. For semisolids, proximal stomach emptying followed the same emptying pattern as the entire stomach, irrespective of the surgical procedure. We concluded that the proximal stomach is the main control for the emptying of liquids and semisolids. The vagal control of overall gastric emptying for semisolids is probably identical to that modulating the intragastric distribution of the meal.

Slower eating rate is independent to gastric emptying in obese minipigs.

The aim of our study was to investigate whether the altered eating behavior observed in the context of a diet-induced metabolic syndrome is related to changes of the gastric emptying and autonomic balance. Eight adult male Göttingen minipigs were subjected during 5months to ad libitum Western diet (WD). Several factors were compared between the lean (before WD) and obese conditions: general activity and eating behavior, gastric emptying, adiposity, glycemia and insulinemia during IVGTT, and heart rate variability (HRV). In our model, obesity did not alter the gastric emptying (258±26 vs. 256±14 min, P>0.10) but induced insulin resistance: increased basal insulinemia (12.6±0.8 to 36.6±6.1 mU/l, P<0.02) and reduced insulin sensitivity (4.5E-4±0.7E-4 to 2.5E-4±0.2E-4 min(-1) per mU.l(-1) of insulin, P<0.05). The HRV and sympathovagal balance were not significantly modified (P>0.10). Fed ad libitum with WD, animals overate durably (P<0.001). During a 30-min meal test though, the ingestion speed, the food ingested (1076±48 vs. 520±52 g) and energy intake decreased in the obese condition (P<0.05), which can be explained by the fragmentation of the daily caloric intake. These data suggest that the slower eating rate and increased number of meals observed in obese minipigs without neuropathy is independent to gastric emptying. The explanation may be sought rather in central modifications induced by obesity that might modify the food perception and/or motivation.

A maternal Western diet during gestation and lactation modifies offspring’s microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs

A suboptimal early nutritional environment (i.e., excess of energy, sugar, and fat intake) can increase susceptibility to diseases and neurocognitive disorders. The purpose of this study was to investigate in nonobese Yucatan minipigs (Sus scrofa) the impact of maternal diet [standard diet (SD) vs. Western diet (WD)] during gestation and 25 d of lactation on milk composition, blood metabolism, and microbiota activity of sows (n = 17) and their piglets (n = 65), and on spatial cognition (n = 51), hippocampal plasticity (n = 17), and food preferences/motivation (n = 51) in the progeny. Milk dry matter and lipid content, as well as plasma total cholesterol and free fatty acid (FFA) concentrations (P < 0.05) were higher in WD than in SD sows. Microbiota activity decreased in both WD sows and 100‐d‐old piglets (P < 0.05 or P < 0.10, depending on short‐chain FAs [SCFAs]). At weaning [postnatal day (PND) 25], WD piglets had increased blood triglyceride and FFA levels (P < 0.01). Both SD and WD piglets consumed more of a known SD than an unknown high‐fat and ‐sucrose (HFS) diet (P < 0.0001), but were quicker to obtain HFS rewards compared with SD rewards (P < 0.01). WD piglets had higher working memory (P = 0.015) and reference memory (P < 0.001) scores, which may reflect better cognitive abilities in the task context and a higher motivation for the food rewards. WD piglets had a smaller hippocampal granular cell layer (P = 0.03) and decreased neurogenesis (P < 0.005), but increased cell proliferation (P < 0.001). A maternal WD during gestation and lactation, even in the absence of obesity, has significant consequences for piglets’ blood lipid levels, microbiota activity, gut–brain axis, and neurocognitive abilities after weaning.—Val‐Laillet, D., Besson, M., Guérin, S., Coquery, N., Randuineau, G., Kanzari, A., Quesnel, H., Bonhomme, N., Bolhuis, J. E., Kemp, B., Blat, S., Le Huërou‐Luron, I., Clouard, C. A maternal Western diet during gestation and lactation modifies offsprings microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs. FASEB J. 31, 2037–2049 (2017). www.fasebj.org

Effect of an abrupt switch from a milk-based to a fibre-based diet on gastric emptying rates in pigs: difference between origins of fibre

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.

Brain processing of duodenal and portal glucose sensing.

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.

Involvement of NO in gastric emptying of semi‐solid meal in conscious pigs

Abstract  The influence of non‐selective nitric oxide synthase (NOS) inhibition on gastric emptying of a semi‐solid meal was studied in conscious pigs. Antro‐duodenal motility and fundic compliance were also assessed to evaluate the mechanisms at the origin of potential alteration in gastric emptying pattern. NG‐nitro‐l‐arginine methyl ester (l‐NAME; 20 mg kg−1 i.v.) delayed gastric emptying (half‐emptying time of 128.98 ± 16.86 min vs 73.74 ± 7.73 min after saline, P < 0.05, n = 6) as a result of decreased proximal gastric emptying. No changes were observed for distal gastric emptying as a result of unchanged antral motility. Similarly, no changes were noted on duodenal motor patterns either in the fasted or in the fed state. l‐NAME decreased fundic compliance in fasted state (49 ± 11 mL mmHg−1vs 118 ± 15 mL mmHg−1 after saline, P < 0.05, n = 6). As this phenomenon is expected to increase emptying rate, the gastroparesis induced by NOS inhibition is thus likely to originate from distal resistive forces. It is concluded that NO positively modulates gastric emptying.

The vagus is inhibitory of the late postprandial insulin secretion in conscious pigs

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.

ACTIVATION CENTRALE À LA SUITE D'UNE STIMULATION VAGALE CHRONIQUE CHEZ LE PORC : APPORTS DE L'IMAGERIE FONCTIONNELLE

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.

Gastric Emptying and Dynamic In Vitro Digestion of Drinkable Yogurts: Effect of Viscosity and Composition

Gastric emptying of food is mainly driven by the caloric concentration, the rheological properties of the chyme, and the physical state (liquid/solid) of food once in the stomach. The present work investigated: (1) The effect of the composition and the viscosity of drinkable yogurts on gastric emptying in pigs, and (2) the behavior of yogurts during dynamic in vitro digestion. Three isocaloric liquid yogurts were manufactured: Two enriched in protein and fiber showing either a low (LV) or high (HV) viscosity, one control enriched in sugar and starch (CT). They were labelled with 99mTc-sulfur colloid and given to pigs (n = 11) to determine gastric emptying pattern by gamma scintigraphy. Then dynamic in vitro digestion of the yogurts was done using the parameters of gastric emptying determined in vivo. Gastric emptying half-times were significantly longer for LV than CT, whereas HV exhibited an intermediate behavior. In vitro gastric digestion showed a quick hydrolysis of caseins, whereas whey proteins were more resistant in the stomach particularly for LV and HV. During the intestinal phase, both whey proteins and caseins were almost fully hydrolyzed. Viscosity was shown to affect the behavior of yogurt in the small intestine.