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From satiation to satiety, the place of sensory pleasure. In a context of increasing obesity, there is an urgent need to understand precisely how the balance between body weight and energy expenditure is managed. To ensure our survival, subtle and sophisticated physiological mechanisms have been developed, including appetite control. Within this framework, sen- sory pleasure, satiation and satiety are key elements in the processes of regulating food intake, Dans un contexte d’augmentation croissante de l’obésité, il devient urgent de comprendre de manière précise comment est géré l’équilibre entre le poids corporel et la dépense éner- gétique. Pour assurer notre survie, des mécanismes physiologiques subtils et sophisti- qués ont été développés, incluant le contrôle de l’appétit. Dans ce cadre, le plaisir sensoriel, le rassasiement et la satiété constituent des éléments clés des processus de régulation de la prise alimentaire.

Feeding is an instinctive behavior accompanied by rewarding feeling of pleasure during obtaining and ingesting food, corresponding to the preparatory and consummatory phases of motivated behavior, respectively. Perception of this emotional state together with alternating feelings of hunger and satiety drives the feeding behavior. Because alterations of feeding behavior including either overeating or anorexia may lead to obesity and cachexia, respectively, understanding the neurochemical mechanisms of regulation of feeding pleasure may help to develop new therapies of these diseases. The dopamine (DA) system of the mesolimbic projections plays a key role in behavioral reward in general and is also involved in regulating feeding-associated pleasure in the forebrain including the nucleus accumbens (NAc) and the lateral hypothalamic area (LHA). It suggests that this DA system can be selectively activated by factors specific to different types of motivated behavior including hunger- and satiety- related hormones. Indeed, central administrations of either orexigenic ghrelin or anorexigenic α-melanocyte-stimulating hormone (α-MSH) increase DA release in the NAc. However, DA has also been shown to inhibit food intake when injected into the LHA, historically known as a « hunger center », indicating DA functional involvement in regulation of both appetite and feeding pleasure. Although both NAc and LHA contain neurons expressing melanocortin receptors, only the LHA receives the α-MSH containing nerve terminals from the α-MSH producing neurons of the hypothalamic arcuate nucleus, the main relay of the peripheral hunger and satiety signals to the brain. A recent study showed that α-MSH in the LHA enhances satiety and inhibits feeding pleasure while potently stimulating DA release in this area during both preparatory and consummatory phases of feeding. It suggests that altered signaling by α-MSH to the DA system in the LHA may be involved in the pathophysiology of obesity and anorexia and the possible underlying mechanisms are discussed.

The gastrointestinal nerves are crucial in the sensing of nutrients and hormones and its translation in terms of control of food intake. Major macronutrients like glucose and proteins are sensed by the extrinsic nerves located around the portal vein walls, which signal to the brain and account for the satiety phenomenon they promote. Glucose is sensed in the portal vein by neurons expressing the glucose receptor SGLT3, which activates the main regions of the brain involved in the control of food intake. Proteins indirectly act on food intake by inducing intestinal gluconeogenesis and its sensing by the portal glucose sensor. The mechanism involves a prior antagonism by peptides of the μ-opioid receptors present in the portal vein nervous system and a reflex arc with the brain inducing intestinal gluconeogenesis. In a comparable manner, short chain fatty acids produced from soluble fibers act via intestinal gluconeogenesis to exert anti-obesity and anti-diabetic effects. In the case of propionate, the mechanism involves a prior activation of the free fatty acid receptor FFAR3 present in the portal nerves and a reflex arc initiating intestinal gluconeogenesis.

Cette thèse avait pour objectif de proposer une nouvelle méthode pour évaluer le rassasiement. Elle s’inscrit plus largement dans le projet FUI Satiarôme, dont le but était de produire des yaourts rassasiants en jouant sur la composition, mais également sur l’arôme et la texture, tout en induisant plaisir et bien être. Les mesures habituelles permettant d’évaluer le rassasiement sont des mesures directes qui peuvent être sujettes à des biais de subjectivité et de désirabilité sociale. Afin de pallier ces biais, nous avons choisi d’orienter notre recherche vers des mesures implicites puisque ce sont des mesures qui ne demandent pas aux sujets d’exprimer leur ressenti et dont les sujets ne sont pas conscients de la nature de la mesure. Nous avons choisi d’utiliser le test d’association implicite (IAT). Ce test permet de déterminer les attitudes des sujets de manière indirecte en mesurant la force d’association relative entre différents concepts par l’enregistrement des temps de réponse. Dans un premier temps nous avons cherché à déterminer si l’évolution de l’état de rassasiement entre la phase pré- et la phase post-consommation pouvait modifier, chez un même individu, la force d’association entre le concept cible (ici « Aliment ») et une valence affective (« Agréable » versus « Désagréable »). Dans un second temps, nous avons voulu déterminer si cette mesure était assez sensible pour discriminer le pouvoir rassasiant de yaourts équicaloriques mais de composition, texture et/ou arôme différents. L’IAT a permis de mesurer un état de rassasiement (avant/après consommation) mais ne semble pas assez sensible pour discriminer le degré de rassasiement entre différents produits.

Rats with an intracardiac chronic catheter were offered dietary self-selection between glucids, proteins and lipids intakes. They are infused continuously with 0.9% NaCl except on the test day with glucose, amino acids or lipids. Parenteral load is about 25% of the daily total food intake. With glucose infusion a selective decrease in glucids intake is observed of about 80% of the caloric glucose load. Aminoacidemic and lipidic infusions lead not only to decrease respectively in proteins and lipids intakes, but also in glucids intakes. So, in this case, total caloric intake decreased more than caloric load. Results are discussed in the hypothesis of existence of a hepatic chemosensibility.

The gustative pleasure evoked by sweet stimuli has been evaluated before and after an oral load of glucose or a lipido-protidic meal without carbohydrates in human subjects in weight balance. The pleasure is decreased (negative alliesthesia) after each of the ingestions.The negative alliesthesia for sweet stimuli is therefore not only a consequence of carbohydrate ingestion but it appears also when other nutriments, mainly proteins or their degradation products, are present in the intestinal tract. These data strongly support the view that the gustative alliesthesia may be connected with short term satiety. The mechanism of gustative alliesthesia is partially unknown; the data presented here suggest the participation of intestinal chemoreceptors specific for amino acids.

There is a real organization of feed choice, with good equilibrium between neuropeptides and neurotransmitters actions, leading to choice and stimulation feeding. Morley described two main systems who control carbohydrate and lipids intake. These data contribute to future therapeutic research.

The ischymetric hypothesis of the control of food intake ( ischys = power in greek) suggests that the physiological stimulus of hunger is characterized by the decrease of the "m etabolisme de fond". In the same way, satiety would occur as long as the MF remains at a high level. The complex problems dealing with the continuous measurement of the MF in the free behaving Rat have been solved recently. As a consequence, it has been possible to test directly the ischymetric hypothesis by measuring the MF oscillations around six meals taken by the same Rat during a 24 hrs. experiment. The results showed that the meals are indeed preceded by a progressive decrease of MF and that the termination of meals coincides with a high metabolic rate. The rapid increase of the MF occurring immediately after the onset of the meals could reflect the oropancreatic reflex inducing the well known anticipatory release and utilization of the endogenous reserves. If anything, the respiratory quotient exhibited only small but not systematic variations during the pre-prandial periods. This observation is in agreement with the ischymetric hypothesis which proposes that the decrease of MF inducing the onset of a meal is due not only to the decrease of the glucose utilization but also to the concomitant decrease of the utilization of the three kinds of metabolic substrates.

The systemic administration of exogenous cholecystokinin (CCK), (a peptide released into the circulation when nutrients arrive in small intestine) provokes inhibition of food intake in numerous animal species and a sensation of satiation in humans. The mechanism involved requires participation of vagal afferent neurons to transmit information, possibly on gastric distension, to brain stem. Two crucial questions remain unanswered: does peripheral endogenous cholecystokinin transport information necessary for satiation at end of normal meals and if so, how and when is this message coded and deciphered; other studies have demonstrated that very small doses of exogenous cholecystokinin (too low to induce satiation if administrated peripherally) will induce satiety if injected into cerebral ventricles or directly into cerebral parenchyma. This suggest but does not prove that cerebral endogenous CCK also plays a role in satiety. It is not known how the satiating action of centrally-administered CCK is related to that of peripherally-administered CCK. Current studies aim at establishing a coherent schema of neuro-endocrine mechanisms implicated (from the gastrointestinal wall via the brain to a motivated behaviour) in the fact that food taken during a meal induces the end of the latter.

Various minor tranquilizers (benzodiazepines, barbiturates and meprobamate) induced an increase in the food intake of rats or mice. Drugs were injected i.p. 30 min before testing and the amount of food consumed during 30 min was recorded. The enhanced food consumption occurred when the animals were in a novel situation, in a situation which they had previously experienced, or in their home cage, in which they were used to eating in the daytime within 30 min. Studies with two benzodiazepines showed this effect to be maximal between 10 to 30 min after injection and to disappear 4 hrs after injection. Moreover, minor tranquilizers reduce the latency before eating of rats and mice tested in a new situation. These results and the observation of anti-anxiety drugs-induced hyperphagia in satiated animals suggest that: 1. The enhanced food consumption of a non familiar food in a novel situation induced by the minor tranquilizers could hardly be related only to their anti-anxiety action. 2. The existence of some inhibitory controls (endogenous satiety in daytime or satiety after recent absorption) is not essential for the action of the minor tranquilizers. 3. An increased motivation and a disruption in the food related behavior could possibly be an explanation for all the observed effects.

Feeding is often influenced by competitive needs or by environmental factors. Nevertheless, in physiological conditions hunger is elicited by depletion of macronutrients. The first question is what specific signals cause food intake? Recent data suggest that the signal comes not from exclusive depletion of carbohydrates or of anyone type of the major macronutrients but from overall decreased cellular power production (hypoischymetric signal). Locomotion free metabolic rate has been shown to decrease preceding hunger and to increase in order to determine satiety. Satiation, which occurs largely before ingested nutrients can cross the intestinal barrier and replete the inner milieu, obeys a specific mechanism. Following the stimulation by ingestion of the oro-gastro-intestinal receptors metabolic hormones such as glucagon and insulin are released and enhance metabolism of endogenous reserves. The so-induced endogenous "meal" brings about an anticipatory hypermetabolism which inhibits further ingestion. Post-absorptive satiety subsequently will replace the pre-absorptive state of satiation. The long term regulation of body weight is more subtle. When the actual body weight exceeds its defended value, responsiveness towards signals of hunger diminishes. This hyporesponsiveness seems to be a consequent of an enlargement of the microscopic fat depot at the level of hypothalamic receptive structures which parallels the peripheral increase of the macroscopic fat depot. Thus, hunger promoting signals become less effective and feeding decreases. A symmetrical process takes place in case of body weight loss which results in central hyperresponsiveness to hunger related stimuli and thus facilitates feeding and body weight recovery.