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Food intake is regulated by both appetite and orosensory reward systems. Appetite systems stimulate or reduce hunger, while orosensory reward motivates consumption of high fat sweet foods, resulting in food enjoyment. The majority of advanced cancer patients suffer from malnutrition and wasting, which may be caused by a loss of appetite due to physiological changes or a hindered orosensory reward system due to taste and smell (chemosensory) changes or both. Orosensory reward systems were hypothesized to be impaired in advanced cancer. To understand the influence of chemosensory alterations on food intake and enjoyment, the nature (intensity) of chemosensory alterations in cancer patients and their relationship with ingestive behaviour and quality of life (QOL) were investigated (study 1). Advanced cancer patients (n=192) more frequently self-reported tastes and odours to be heightened rather than diminished (p=0.035). Patients with perceived chemosensory alterations had poorer QOL (p=0.0176) and lower caloric intake (p=0.0018) compared to patients with no alterations. Cannabinoids (e.g. -9-tetrahydrocannabinol, -9-THC) increase food intake by stimulating both appetite and orosensory reward systems as well as potentially enhancing chemosensory function. To palliate chemosensory alterations and poor appetite, advanced cancer patients (n=21, study 2) with these symptoms were randomized to receive either -9-THC (2.5mg) or placebo oral capsules twice daily for 18 days. Compared to patients receiving placebo, -9-THC-treated patients reported that food tasted better (p=0.04), they had improved chemosensory perception (p=0.026), increased preference and intake of high protein foods (p=0.008), and improved appetite (p=0.05), quality of sleep (p= 0.025), and relaxation (p= 0.045). Like cancer patients, tumour-bearing rats appeared to experience a loss of orosensory reward, showing tumour-associated anorexia when fed a rewarding diet to the same degree as on a usual diet (study 3). -9-THC significantly increased caloric intake compared to vehicle for both tumour-bearing (p=0.0146) and healthy rats (p=0.0004), suggesting endocannabinoid-mediated appetite systems are functioning in this tumour model. The findings of this thesis suggest orosensory reward systems to be impaired in advanced cancer, decreasing the liking and motivation to eat. -9-THC treatment may help to palliate perceived chemosensory alterations and loss of appetite and food enjoyment in advanced cancer. / Food Science and Technology

Les attentes sociétales s’orientent vers une consommation saine, et provenant de systèmes agricoles durables. En filière cunicole, la maîtrise des pathologies digestives nécessite le recours à l'antibiothérapie curative ou préventive. La recherche d’alternatives à l’utilisation d’antibiotiques en élevages cunicoles est donc primordiale pour augmenter la durabilité de cette production. Les stratégies de limitation de la quantité d’aliment ingérée sont une des solutions possibles à ce problème, puisqu'elles améliorent la résistance du jeune lapin aux troubles digestifs. Ce travail de thèse a pour objectif d’étudier les mécanismes sous-jacents à cet effet favorable des stratégies de rationnement, et aussi d'analyser le comportement alimentaire du lapin restreint en relation avec son bien-être. Cet objectif se scinde en deux parties étudiées. La première partie a pour but de déterminer quelle caractéristique de la restriction alimentaire limite les troubles digestifs en engraissement. La seconde partie s’intéresse aux paramètres biologiques potentiellement influencés par cette stratégie d’alimentation. Les paramètres considérés sont reliés à plusieurs domaines de biologie : enzymologie, histométrie, écosystème bactérien cæcal. Une restriction de l'ingéré de -25% réduit la croissance mais améliore significativement l’efficacité digestive (de 4 à 6% entre 28 et environ 50 jours d'âge) des lapins en engraissement, qui peut s'expliquer par une plus forte digestibilité des fractions protéique (4,5%), énergétique (5,3%) et fibreuses (NDF : 8,9%, ADF : 9,7%, hémicelluloses: 7,9%, cellulose : 11,5%). Cependant, la structure, la diversité et la densité de la communauté bactérienne cæcale sont peu modifiées chez l'animal restreint sain. Des modifications du comportement alimentaire ont été soulignées au cours de ce travail. Ainsi, le rythme d’ingestion, fonction du rythme nycthéméral pour les lapins nourris à volonté, est dépendant du moment de distribution de l’aliment pour les animaux restreints. Après 18 jours de restriction, les lapins ingèrent un tiers de la quantité qui leur est distribuée en 2 heures, et la totalité en moins de 10 heures. Mais aucune agressivité ou compétition n’a été observée entre les animaux restreints. Plusieurs pistes peuvent expliquer l’efficacité de cette stratégie d’alimentation sur la santé digestive du lapereau. Ainsi, les résultats obtenus au cours de la reproduction d’une colibacillose (Escherichia coli O128:C6) suggèrent une stabilisation de l’écosystème iléal par la restriction alimentaire après l’infection. D'autre part, au niveau cæcal l'activité des communautés bactériennes serait modulée, même si pour ce modèle, l'effet d'une ingestion limitée semble faible sur le statut sanitaire. Enfin, l’alternance de périodes de satiété et de périodes de faim stimule la libération sanguine d’hormones (ghréline notamment) qui pourraient moduler la fonction immunitaire. En perspectives, il serait pertinent d'étudier plus précisément les fonctions liées au statut immunitaire ou endocrinologique. De plus, l'étude plus approfondie de la communauté bactérienne cæcale, en ciblant certaines espèces, pourrait apporter un complément d’informations sur les interactions entre ingestion et symbiote digestif et lors d'une approche comparée de 2 modèles pathogèniques : EPEC vs. EEL. / Societal expectations are moving towards healthy food from sustainable farming systems. In rabbit industry, control of digestive diseases requires the use of curative or preventive antibiotics. The search for alternatives to the use of antibiotics in rabbit breeding is thus crucial to improve sustainability of this production. Strategies for limiting the amount of feed ingested are one possible solution to this problem, since they improve the digestive resistance of young rabbits. This thesis aims to study the mechanisms underlying this positive effect of restriction strategies, and also to analyze the feeding behaviour of restricted rabbit in relation to their welfare. This objective is divided into two parts. The first part aims to determine which characteristic of feeding restriction limits the digestive disorders in fattening. The second part deals with the biological parameters potentially influenced by this feeding strategy. The parameters considered are related to several areas of biology: enzymology, histometry, digestive bacterial ecosystem A reduction of feed intake of -25% reduced growth, but significantly improved digestive efficiency (4 to 6% between 28 and 50 days old) of fattening rabbits which can be explained by a higher protein digestibility (4.5%), energy (5.3%) and fibres (NDF: 8.9%, ADF: 9.7%, hemicellulose 7.9%, cellulose: 11.5%). However, the structure, diversity and density of the caecal bacterial community are little changed in the healthy animal fed restricted. Changes in eating behaviour were highlighted during this work. Thus, the rhythm of intake, depending on the circadian rhythm in rabbits fed ad libitum, is function of the feed distribution time for restricted animals. After 18 days of restriction, rabbits ingest in 2 hours the third of the quantity supplied, and the entire amount within 10 hours. No aggression or competition was observed between animals. Several hypotheses could explain the effectiveness of this strategy on digestive health in young rabbit. Thus, the results obtained during the reproduction of colibacillosis (Escherichia coli O128: C6) suggest a stabilization of the ileal ecosystem after infection. On the other hand, the main activity of bacterial communities of caecum would be modulated, even if for this model a limited intake moderately modified the sanitary status. Finally, the alternation of periods of satiety and hunger may stimulate the release of hormones (e.g. ghrelin) that could modulate immune function. In perspective, it would be appropriate to study more precisely the functions related to immune or endocrine status.In addition, a deeper study of the caecal bacterial community by targeting some species could provide additional informations on the interactions between intake and digestive symbiote, and on a comparative approach of the two pathogenic models: EPEC vs. REE.

La Sclérose Latérale Amyotrophique (SLA) est une maladie neurodégénérative due à la dégénérescence des motoneurones supérieurs et inférieurs. La perte des neurones moteurs entraine une atrophie puis une paralysie progressive des muscles. En plus de la perte musculaire, une perte de poids est importante chez les patients SLA. Ce symptôme apparaît avant les premiers symptômes moteurs et est corrélé avec la survie. Ce défaut du métabolisme énergétique est en partie dû à un hypermétabolisme associé à des problèmes de prise alimentaire. L’hypothalamus est la partie du cerveau contrôlant l’ensemble du métabolisme énergétique. L’objectif de ma thèse a été de caractériser les altérations hypothalamiques dans la SLA. Nous avons tout d’abord mis en évidence une anomalie du système mélanocortine de l’hypothalamus, et montré que cette anomalie était associée à des modifications du comportement alimentaire. Ensuite, nos travaux ont mis en évidence une atrophie de la partie postérieure de l’hypothalamus, comprenant l’aire hypothalamique latérale (LHA), des patients SLA, corrélée à la perte de poids. Finalement, nous démontré que les neurones produisant le MCH, situés dans le LHA, sont atteints dans la SLA et qu’une complémentation en MCH empêche la perte de poids dans un modèle animal de SLA. / Amyotrophic Lateral Sclerosis (ALS) is a major neurodegenerative disease characterised by a loss of upper and lower motor neurons. The loss of motor neurons leads to muscle atrophy and paralysis. Besides motor loss, weight loss is important in ALS patients. This symptom appears before first muscular symptoms and is correlated with survival. This defect of energetic metabolism is partially due to hypermetabolism associated with food intake problems. Hypothalamus is the part of brain controlling the energetic metabolism. The aim of my Ph.D. was to characterise hypothalamic alterations in ALS. First, we have shown a default in the melanocortin system of hypothalamus, and shown that this melanocortin defect correlates with alterations in food intake behaviour. Second, we demonstrated the existence of hypothalamic atrophy in ALS patients in the posterior part of the hypothalamus, including the lateral hypothalamic area (LHA). This atrophy was correlated with weight loss. Finally, we observed that hypothalamic MCH neurons, located in the LHA, are affected in ALS, and that MCH complementation rescues weight loss in a mouse model of ALS.

D. Tech. (Department of Tourism and Hospitality Management, Faculty of Human Sciences) Vaal University of Technology. / The elderly in Nigeria are used to consuming foods that are inadequate in providing the required amount of nutrients for a healthy living due to uninformed food choices and dietary food intake habits. The main objective of this study was to determine the impact of the developed food and nutrition guidelines on the dietary behaviour of the elderly in Ondo West city Ondo, Nigeria. The developed food and nutrition guidelines were used to generate a training manual for the caregivers’ in order to apply and disseminate the correct information about food nutrients and food choices to the elderly through the knowledge acquired in the nutrition education training programme by the caregivers. A baseline study was conducted making use of the measuring instruments namely, socio-demographic questionnaire, 24-hour recall, food frequency questionnaire completed by the elderly attending the old people’s home and a nutrition knowledge questionnaire to test the nutrition knowledge of the caregivers. The methodology for the study was in six phases: Phase 1: is about the baseline survey, involving the training of fieldworkers, administering and completing questionnaires: Socio-demographic, 24-hour recall, food frequency questionnaire (FFQ), by the elderly and the nutrition knowledge questionnaire (NKQ) by the caregivers. Phase 2: It involved the planning and development of food and nutrition guidelines for the caregivers of the elderly. Phase 3: This phase is about the training of the caregivers by the researcher, making use of the developed training manual with information sourced from the developed food and nutrition guidelines. Phase 4 was about the intervention programme in the study, i.e. the nutrition education programme (NEP) using information from guidelines of USA, Europe, New Zealand, South Africa, Nigeria and adapted FAO framework. Phase 5 was about the evaluation of the study, involving the completion of the nutrition knowledge questionnaire (NKQ), by the caregivers on post-test assessment after intervention, conducting observation and group interview. Phase 6 involved determining the impact of the food and nutrition guidelines and conducting a post-test making use of the research instruments, 24-hour recall, and food frequency questionnaires (FFQ) with the main objective drawn and followed up by the conclusion and recommendations in the study. A content analysis of both the observation and focus group discussion resulted in compliance with the food and nutrition guideline specifications and a remarkable improvement on food preparation skills and performance of the old people’s homes’ personnel. The main findings in the study revealed that consistent and, full compliance, with effective implementation of the food and nutrition guidelines would improve the older people’s dietary behaviour and food consumption patterns. The NEP did not improve the knowledge of the caregivers at the expected rate and level because of the low-level basic scientific background of the caregivers. The socio-demographic questionnaire revealed that 61.7% of those researched were females and 38.3% males with an average age between 60 and 65 years; 54% were married with a household income between N20001- N50000 and majority of them spending between N10001-N15000 on two meals (40%) and three meals (30%). The result from 24-hour recall and the food frequency (FFQ) questionnaires indicated that, the intake of energy, calcium and fiber were below the recommended daily allowance (RDA), while protein and carbohydrate were higher, with an emphasis on starchy foods. The nutrition knowledge questionnaire (NKQ) identified the need for higher level of food and nutrients by the caregivers in their responsibility to the elderly, for improvement in their healthy dietary habits as indicated in the four sections of NKQ results (A, B, C and D). The consumption of fruits and vegetables were impressively high, after the intervention compared to before. Moreover, there was a drastic reduction in the consumption of carbohydrate-sourced food items, fat, sugar and salt as informed by the developed guidelines. Conclusively, the study was able to establish a reliable basis on the improvement of nutrient based dietary intake with the effective utilisation of available information in the guidelines. Also, awareness was created for the elderly to improve their eating habits through the exposure of the caregivers to training on nutrition knowledge. The researcher recommended an in-house organized refresher programme which should take place periodically and consistently on the information in the developed nutrition guidelines along with encouraging the personnel in the handling of foods (caregivers, chefs, cooks) for effective implementation.