Caroline Clouard

Food preferences and aversions in human health and nutrition: how can pigs help the biomedical research?

The establishment of food preferences and aversions determines the modulation of eating behaviour and the optimization of food intake. These phenomena rely on the learning and memory abilities of the organism and depend on different psychobiological mechanisms such as associative conditionings and sociocultural influences. After summarizing the various behavioural and environmental determinants of the establishment of food preferences and aversions, this paper describes several issues encountered in human nutrition when preferences and aversions become detrimental to health: development of eating disorders and obesity, aversions and anorexia in chemotherapy-treated or elderly patients and poor palatability of medical substances and drugs. Most of the relevant biomedical research has been performed in rodent models, although this approach has severe limitations, especially in the nutritional field. Consequently, the final aim of this paper is to discuss the use of the pig model to investigate the behavioural and neurophysiological mechanisms underlying the establishment of food preferences and aversions by reviewing the literature supporting analogies at multiple levels (general physiology and anatomy, sensory sensitivity, digestive function, cognitive abilities, brain features) between pigs and humans.

Exposures to Conditioned Flavours with Different Hedonic Values Induce Contrasted Behavioural and Brain Responses in Pigs

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 (FGlu), lithium chloride (FLiCl), or saline (control treatment, FNaCl). 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 18FDG 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 FLiCl than the FNaCl or FGlu meals. During the two-choice tests performed one and five weeks later, the FNaCl and FGlu foods were significantly preferred over the FLICl food even in the absence of i.d. infusions. Surprisingly, the FNaCl food was also preferred over the FGlu 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.

Impact of sensory feed additives on feed intake, feed preferences, and growth of female piglets during the early postweaning period

Our study aimed at investigating the effect of feed supplementation, from weaning, with 3 sensory feed additives (FA1, FA2, and FA3) on feed preferences, feed intake, and growth of piglets. The FA1 contained extract of Stevia rebaudiana (10 to 20%), extract of high-saponin plants (5 to 10%), and excipients (70 to 85%), the FA2 was mainly composed of a natural extract of Citrus sinensis (60 to 80%), and the FA3 was made of a blend of extracts of hot-flavored spices (5 to 15%) and excipients (85 to 95%). At weaning (d 1), a total of 32 female piglets housed in individual pens were allocated to 4 treatments (FA1, FA2, FA3, and control [CON]) of equivalent mean weight. The pigs were fed a standard pelleted prestarter diet from weaning (d 1) to d 15 and a starter diet from d 16 to 28. The diets were supplemented with the feed additives (FA) corresponding to their treatment, while the CON treatment was the standard diets with no additive. Feed refusals were weighed daily and piglets were weighed weekly on d 1, 7, 14, 21, and 28. On the day of feed transition (d 16) as well as 7 (d 23) and 10 d (d 26) later, the animals were consecutively subjected to 1- and 22-h double-choice feeding tests to investigate their preferences during a short period and a longer period of time for the CON starter diet and the starter diet added with the FA corresponding to their treatment. No overall effect of the feed additives was observed on ADFI, ADG, G:F, and final BW. No overall preference was highlighted for the FA1 treatment, except for a preference for the FA1 starter diet during the 1-h test on d 23 (78% of total feed intake; P < 0.01). For the FA2 treatment, the pigs consumed the FA2 starter diet more than the CON starter diet during the 22-h tests on d 16 (67% of total feed intake; P < 0.05) and 26 (62% of total feed intake; P < 0.01). For the FA3 treatment, on d 26, the FA3 starter diet was and tended to be consumed more than the CON starter diet during 1- (69% of total intake; P < 0.05) and 22-h (60% of total intake; P < 0.10) tests, respectively. In conclusion, feed supplementation with the FA1, FA2, and FA3 from weaning did not induce beneficial effects on feed intake and growth performance during the early postweaning period. The FA2 increased palatability and acceptance of the unfamiliar starter diet the day of feed transition, while the FA1 and FA3 increased palatability of the starter diet only after a few days of exposure, most likely through long-term familiarization processes.

Combined compared to dissociated oral and intestinal sucrose stimuli induce different brain hedonic processes

The characterization of brain networks contributing to the processing of oral and/or intestinal sugar signals in a relevant animal model might help to understand the neural mechanisms related to the control of food intake in humans and suggest potential causes for impaired eating behaviors. This study aimed at comparing the brain responses triggered by oral and/or intestinal sucrose sensing in pigs. Seven animals underwent brain single photon emission computed tomography (99mTc-HMPAO) further to oral stimulation with neutral or sucrose artificial saliva paired with saline or sucrose infusion in the duodenum, the proximal part of the intestine. Oral and/or duodenal sucrose sensing induced differential cerebral blood flow changes in brain regions known to be involved in memory, reward processes and hedonic (i.e., pleasure) evaluation of sensory stimuli, including the dorsal striatum, prefrontal cortex, cingulate cortex, insular cortex, hippocampus, and parahippocampal cortex. Sucrose duodenal infusion only and combined sucrose stimulation induced similar activity patterns in the putamen, ventral anterior cingulate cortex and hippocampus. Some brain deactivations in the prefrontal and insular cortices were only detected in the presence of oral sucrose stimulation. Finally, activation of the right insular cortex was only induced by combined oral and duodenal sucrose stimulation, while specific activity patterns were detected in the hippocampus and parahippocampal cortex with oral sucrose dissociated from caloric load. This study sheds new light on the brain hedonic responses to sugar and has potential implications to unravel the neuropsychological mechanisms underlying food pleasure and motivation.

An attempt to condition flavour preference induced by oral and/or postoral administration of 16% sucrose in pigs

The present study investigated the acquisition of conditioned flavour preferences in pigs using the caloric value and/or sweet taste of sucrose. Nine water-deprived juvenile pigs were given four three-day conditioning sessions during which they received flavoured solutions as conditioned stimuli (CS). The CS solutions were paired with three treatments that generated a gustatory and/or a caloric reinforcement (US). The CS++ solution was added with 16% sucrose and paired with an intraduodenal (ID) infusion of water, the CS+ solution was paired with an ID infusion of 16% sucrose and the CS- solution was paired with an ID infusion of water. One and two weeks after conditioning, the water-deprived pigs were subjected to two-choice preference tests with the unreinforced CS solutions. Solutions intake, behavioural activity and some drinking parameters were measured. Despite no difference in CS intake during conditioning, the animals spent less time inactive and more time standing during CS++ than CS+ conditioning. When receiving CS++, the pigs explored the drinking trough more than when receiving CS-. Compared to the CS- condition, the numbers of drinking episodes and intra-drinking episode (IDE) pauses were also 36% and 49% lesser in the CS++ condition, but these differences were not significant. During the two-choice tests, the pigs did not show significant preferences. Nevertheless, during the first session, the pigs seemed to show a slight preference for the CS++ (57% of total intake) compared to CS+. The duration of CS++ drinking episodes represented 64% of the total duration compared to CS+ and CS- . The total time spent drinking the CS++ also represented 57% of the total time in the CS++ vs. CS- test. To conclude, although no clear-cut preferences were found during two-choice tests, the oral perception of 16% sucrose during conditioning induced changes in behavioural activities, motivational responses and microstructure of CS intake, suggesting the importance of oral food perception for food selection processes in pigs. Further studies are needed to investigate the impact of water deprivation on the expression of flavour preferences in pigs.

Familiarity to a Feed Additive Modulates Its Effects on Brain Responses in Reward and Memory Regions in the Pig Model.

Brain responses to feed flavors with or without a feed additive (FA) were investigated in piglets familiarized or not with this FA. Sixteen piglets were allocated to 2 dietary treatments from weaning until d 37: the naive group (NAI) received a standard control feed and the familiarized group (FAM) received the same feed added with a FA mainly made of orange extracts. Animals were subjected to a feed transition at d 16 post-weaning, and to 2-choice feeding tests at d 16 and d 23. Production traits of the piglets were assessed up to d 28 post-weaning. From d 26 onwards, animals underwent 2 brain imaging sessions (positron emission tomography of 18FDG) under anesthesia to investigate the brain activity triggered by the exposure to the flavors of the feed with (FA) or without (C) the FA. Images were analyzed with SPM8 and a region of interest (ROI)-based small volume correction (p < 0.05, k ≥ 25 voxels per cluster). The brain ROI were selected upon their role in sensory evaluation, cognition and reward, and included the prefrontal cortex, insular cortex, fusiform gyrus, limbic system and corpus striatum. The FAM animals showed a moderate preference for the novel post-transition FA feed compared to the C feed on d 16, i.e., day of the feed transition (67% of total feed intake). The presence or absence of the FA in the diet from weaning had no impact on body weight, average daily gain, and feed efficiency of the animals over the whole experimental period (p ≥ 0.10). Familiar feed flavors activated the prefrontal cortex. The amygdala, insular cortex, and prepyriform area were only activated in familiarized animals exposed to the FA feed flavor. The perception of FA feed flavor in the familiarized animals activated the dorsal striatum differently than the perception of the C feed flavor in naive animals. Our data demonstrated that the perception of FA in familiarized individuals induced different brain responses in regions involved in reward anticipation and/or perception processes than the familiar control feed flavor in naive animals. Chronic exposure to the FA might be necessary for positive hedonic effects, but familiarity only cannot explain them.

O62: Détection combinée ou dissociée du sucre aux niveaux gustatif et/ou viscéral : conséquences sur les processus hédoniques cérébraux

Introduction et but de l’etude La caracterisation des reseaux cerebraux impliques dans le traitement des signaux sucres gustatifs et/ou visceraux chez un modele animal pertinent en nutrition humaine pourrait aider a mieux comprendre les mecanismes centraux lies au controle de l’ingestion et les causes potentielles de certains troubles du comportement alimentaire. Cette etude d’imagerie cerebrale avait pour objectif de comparer les reponses cerebrales induites par la detection dissociee ou combinee de saccharose aux niveaux oral et/ou intestinal, chez le porcelet en croissance. Materiel et methodes Sept animaux ont ete soumis, sous anesthe-sie generale a l’isoflurane, a quatre seances d’imagerie cerebrale par tomographie d’emission monophotonique ( 99m Tc-HMPAO) lors d’une exposition a une stimulation orale avec de la salive artificielle neutre (OS-) ou sucree (OS+), couplee a une infusion duodenale de serum physiologique (DS-) ou de saccharose (DS+). Trois contrastes cerebraux ont ete analyses via le logiciel SPM8 : OS+DS+ vs. OS-DS-, OS+DS- vs. OS-DS-, et OS-DS+ vs. OS-DS- pour etudier les reponses a des stimulations sucrees associant ou dissociant les modalites gusta-tives et viscerales, respectivement. Une analyse SVC (Small Volume Correction) a ete realisee sur la base de regions d’interet incluant les noyaux de la base, les cortex prefrontal, insulaire et cingulaire, l’hippocampe et le cortex parahippocampique, ainsi que l’amygdale. Le seuil de significativite des pics de clusters a ete fixe a P Resultats et Analyse statistique Les resultats de cette etude montrent que la detection du saccharose aux niveaux oral et/ou duodenal a induit des modifications du debit sanguin locoregional cerebral (indicateur de l’activite cerebrale) dans des regions connues pour etre impliquees dans la memoire, les processus hedoniques et motivationnels, ainsi que l’evaluation de stimuli sensoriels. Ces regions incluent le striatum dorsal, le cortex prefrontal, le cortex cingulaire, le cortex insulaire, l’hippocampe et le cortex parahippocampique. La detection duodenale de saccharose (avec ou sans perception gustative) a induit des activations specifiques dans le putamen, le cortex cingulaire ventral anterieur et l’hippocampe. Des baisses d’activite cerebrale ont ete detectees dans les cortex prefrontal et insulaire uniquement lorsque le gout sucre etait percu oralement (avec ou sans detection duodenale). Enfin, l’activation du cortex insulaire droit a seulement ete observee lors de la detection combinee du saccharose aux niveaux oral et duodenal, tandis que des activations specifiques ont ete enregistrees dans l’hippocampe et le cortex parahippocampique en contexte de stimulation gustative dissociee d’une charge calorique. Conclusion Cette etude apporte de nouveaux elements sur les reponses cerebrales au sucre et permet d’accroitre notre connaissance des mecanismes neuropsychologiques gouvernant plaisir et motivation alimentaire. Notamment, ces resultats demontrent l’importance de la detection multimodale du sucre sur la modulation du circuit de la recompense et permettent d’emettre des hypotheses quant aux consequences centrales et comportementales de l’utilisation de succedanes du sucre, comme les edulcorants, ou bien sur la consommation excessive de regimes sucres et hypercaloriques sur la mise en place de phenomenes addictifs.