Age-related macular degeneration (AMD) is responsible for 50 % of the cases of blindness in industrialized countries. It results from a pathological ageing of the retina, linked to a dysfunction of the retinal pigment epithelium (RPE), responsible for the recycling of the photoreceptors outer segments and for the nutritional exchanges with the blood circulation, through the vascular choroid (CH). Current treatments are limited to the neovascular form of the disease, and cannot always avoid severe visual loss. Thus, preventive strategies aiming at the reduction of the incidence of AMD are still of major public health importance, as they may reduce the costs associated to the treatment of neovascular AMD, but also to the loss in autonomy and quality of life associated with AMD-related visual impairment. N-3 polyunsaturated fatty acids (PUFA) and cholesterol metabolisms are highly suspected to play a role in AMD pathophysiology. Indeed, epidemiological studies have very consistently shown a 40% reduction in risk for AMD in subjects with high dietary intake of n-3 PUFA, and in particular long-chain n-3 PUFA docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). In order to better understand the role of n-3 PUFA in retinal ageing, there is a need to identify reliable circulating biomarkers of n-3 PUFA retinal status. In an innovative approach using comprehensive lipidomics in a preliminary post-mortem study, we recently developed and identified several good candidates to be circulating biomarkers of n-3 PUFA retinal status. Whether these circulating biomarkers of lipid status may be associated with AMD remains to be determined. Besides, impairment of cholesterol metabolism in AMD was suggested by histological, experimental and genetic studies. HDL and LDL lipoproteins are carriers of n-3 PUFA to the retina. CETP (cholesterol ester transfer protein) and LCAT (lecithin-cholesterol acyltransferase) are key proteins in the remodeling of cholesteryl esters (CE) in lipoproteins. Among others, a gene polymorphism in CETP was associated with the risk of AMD. The results of our previous post-mortem study also suggested that the ratio of the DHA concentration in plasma CE to the DHA concentration in plasma phosphatidylcholines (PC) may represent a biomarker of the concentration of DHA in the RPE/CH. This ratio can be considered as an indirect indicator of the LCAT enzyme activity, which is responsible for the plasma CE synthesis in HDL. All these data comfort the implication of cholesterol metabolism in the transfer of n-3 PUFA to the retina. The objective of the proposal is to overcome two challenges: - A scientific one, to better understand the role of n-3 PUFA, cholesterol metabolism, and their interaction in AMD. - A technological one, to identify and validate new biomarkers of lipid status with high discriminative value for AMD. The multidisciplinary project will combine a case-control study of AMD, allowing the identification of biomarkers associated with AMD and two post-mortem studies allowing the study of the associations of these biomarkers with ocular n-3 PUFA status (retina, RPE/CH), firstly in elderly donors without AMD and secondly in eyes from donors affected by AMD. It represents a first step towards the design of a large scale interventional study, aiming at the reduction of the incidence of AMD with supplementation in n-3 PUFA. By studying a major aspect of retinal ageing, which has considerable repercussions on the wellbeing and autonomy of elderly subjects, the present project perfectly fits in the “health and wellbeing” challenge (3.4), and particularly of subtheme 12 “Normal and pathological ageing, autonomy and quality of life”.

Context. Occidental countries have to face a dramatic expansion of metabolic diseases, including obesity and diabetes, representing a major health burden in industrialized societies. The rapid increase in prevalence of these metabolic diseases is likely due to changes in environment and lifestyle, generating “obesogenic” conditions linked to an excessive energy intake. In healthy animals, food intake is permanently adjusted to fit with the cumulative energy expenditure. This remarkable energy stability is finely tuned by the central nervous system after a permanent monitoring of numerous metabolic signals within discrete brain areas. A thorough understanding of the neural mechanisms controlling food intake and metabolism will definitely help finding ways to stop the expansion of metabolic diseases. The hypothalamus, which ensures long-term stability of the inner milieu, is of major importance in the control of energy balance. Interestingly, the hypothalamus remains “plastic” in the adulthood, meaning that neuronal networks in this structure can undergo functional or morphological remodeling aimed at integrating environmental and internal conditions. Interestingly, genome-wide association studies in human have reported a strong association between high body-mass index and polymorphic loci whose genes are highly expressed in the brain and involved in neuronal plasticity. Moreover, haploinsufficiency of BDNF, a factor that mediates brain plasticity, is associated with childhood-onset obesity. These studies suggest that brain plasticity may play a role in regulating energy balance in humans. Indeed, we recently showed that plasticity of feeding circuits is required for the homeostatic regulation of food intake in mice. We identified the polysialic acid (PSA), a complex sugar modulating cell-to-cell interaction, as a mediator of the plasticity of feeding circuits. Furthermore, genetic or pharmacological removing of PSA is obesogenic. We propose to pursue our work on neural control of appetite and metabolism in mice with a powerful nutrigenomic approach to uncover molecular bases of PSA biosynthesis at the chromatin level. Objectives of the proposal and expected results. Biological explanation underlying individual predisposition to obesity and its complications are still lacking. Since PSA-dependent hypothalamic plasticity is required for homeostatic regulation of food intake, we postulate that low individual capacity of neuronal rewiring due to low hypothalamic PSA level could explain metabolic inflexibility, intolerance to dietary fat, and vulnerability to diet-induced obesity (DIO). Thus, main objectives of the project are to determine the link between hypothalamic PSA level and obesity, and to uncover molecular mechanisms underlying PSA-triggered homeostatic control of energy balance. We expect to show that low hypothalamic PSA level predisposes to DIO, and that PSA supplementation is a conceptual basis for a therapy to promote loss of weight during obesity. Next, we want to describe the chromatin-remodeling events that are crucial for PSA synthesis and for regulation of food intake. This fundamental analysis is a prerequisite allowing us to identify exhaustively all the signaling pathways activated in the hypothalamus during metabolic imbalance. We will determine whether the methylation state of St8sia4, a gene involved in polysialylation, is linked to predisposition to DIO. Methods. The team has expertise in fields of Nutrition, Metabolism and Neurosciences, and skills from behavior to molecule analysis to complete the objectives. This project relies on the use of three specific fronts of science: (i) state-of-the-art molecular biology to perform original and accurate investigation of molecular processes stimulated during a metabolic switch (i.e. in vivo chromatin immuno-precipitation, proteomic); (ii) functional exploration of energy metabolism; and (iii) gene and pharmacological manipulation in the adult hypothalamus.

PUNCH is a collaborative project which aims at providing efficient proposals in order to favor healthier eating behavior in children (3 months-11 years), beyond traditional approaches based on health-related information. Eating behavior will be studied in qualitative (“what” is eaten) and quantitative (“how much” is eaten) terms. PUNCH aims at (1) better understanding the determinants of infant and children’s eating behavior, by taking into account sociological, psychological, experiential, and sensory factors and (2) evaluating the effectiveness of innovative levers of actions in order to modify school-aged children’s eating behavior, exploring tracks suggested by cognitive psychology, behavior science, economics and marketing. The proposed approaches are experimental, with the exception of the sociologic approach. Interdisciplinary, PUNCH associates complementary domains of expertise (6 academic partners). PUNCH is organized as follows: WP0: Coordination; WP1: Understanding determinants of eating behavior (WP1.1. Early determinants of capacity to control energy intake; Task 1.1.1 Impact of socialization on capacity to control energy intake; Task 1.1.2 Impact of milk feeding mode on capacity to control energy intake; WP1.2. Describing responses to food pleasure; Task 1.2.1 Influence of sensory factors on food choices; Task 1.2.2 Using brain imaging techniques to image pleasure; Task 1.2.3 Defining children’s cognitive profiles toward pleasure); WP2: Promoting children's healthy eating behavior (Task 2.1: harmonization of the procedures; Task 2.2: Assessing effect of intervention by measuring paternalism; Task 2.3: Assessing effect of priming on food choices; Task 2.4: Assessing effect of nudging on portion size); WP3: Dissemination (Task 3.1 Roadmap to future actions ; Task 3.2 Final event and dissemination). The main expected results of PUNCH are: -To produce the scientific grounds towards healthier eating behavior in children that could be easily transferred into practice by small changes in children’s environment (i.e. food quality, information, training and parental feeding practices), -To produce the scientific grounds to indicate if it is easier to modify children’s food choices directly or through their parents, - To suggest evidence-based recommendations that would target specific groups of individuals, - In fine, to help to produce public health recommendations taking into account not only nutrition, but also social, psychological and sensory aspects of eating behavior, that could be implemented in tools for health and childhood professionals such as the Programme National Nutrition Santé guides.

The few available studies in the Caribbean, including the French West Indies, highlight urgent public health issues: a shift in the dietary structure and increasing rates of obesity and chronic diseases have been observed over recent decades, revealing an advanced phase of the nutrition transition, which may affect nutrition security. Among the striking characteristics of nutrition transition are changes in food supply and population diet over short periods related to international trade and increased dependence on foods’ importation. An in-depth knowledge of individual and environmental determinants of dietary behaviours in French West Indies is urgently needed to better understand how they impact population health and to guide public health measures. Our multidisciplinary project, involving nutritionists, epidemiologists, economists, sociologists, sensory scientists, a food technical institute, food industries and the French Ministry of Agriculture, aims to elucidate the relationships between characteristics of local food supply and dietary behaviours of populations and to propose strategies to improve nutrition security in the French West Indies. Specifically, our project aims at: -characterizing individual food and nutrient intakes, nutritional status and household food supply practices (WP1). Based on epidemiological representative studies conducted in 2004 among 1113 Martinican adults and in 2014 among 1273 Martinican and Guadeloupean adults and 153 children, we will characterize dietary patterns, in relation with the prevalence of obesity, folate and iron deficiencies as well as their social determinants and their evolution over 11 years. -understanding determinants of consumers’ food choices (WP2). We will assess sensory preferences for sweet, fat and salt in Martinican adults, by developing sensory tests and preference questionnaire adapted to the population. We will study their relationships with dietary intake, through 24h dietary records. We will also evaluate how consumers balance different motives (price, sensory preference, product characteristics, local production) using experimental economics. Then, we will qualitatively explore how food environment influence consumers’ food practices. -characterizing the evolution of food supply and the rooms for manoeuvre for local firms to improve the nutritional quality of foods (WP3). Using interviews, we will characterize supply chain and strategies of different stakeholders in the French West Indies. We will study dynamics of food products’ importations and local production in terms of price, amounts, nutritional quality and types of foods, over two decades in Martinique and Guadeloupe, using existing data from custom duties and local production. Rooms for manoeuvre for local firms, in terms of nutritional improvement of foods (reformulation, redeployment and innovation) will be estimated. -exploring strategies, at consumer and food supply levels, able to improve nutrition security. Based on findings on firms’ rooms of manœuvre, we will simulate the impact of reformulations on the nutritional quality of individual observed diets, i.e. when no changes occur at consumer level. Based on findings on consumers’ behaviours, and when no changes occur at food supply level, we will model the dietary changes allowing meeting nutritional recommendations with lowest departure from observed food patterns and at no additional cost. Then, the potential impact on nutrition security of combining improvements of food supply and food choices will be explored through quantitative and qualitative approaches, in order to suggest guidelines for public and private decision makers. By proposing ways to improve nutrition security through more favorable dietary behaviors and local food supply accessible and conducive to well-being and health, our project will contribute to identify and to promote strategies to meet the nutritional and hedonic needs of consumers under their budget constraints.

The general objective of the project is to investigate the role of multisensory integration in the ability to recognize and understand facial emotion, by considering both developmental aspects in infancy and neuropsychological aspects in schizophrenia. The main hypothesis is that multisensory integration boosts the ability to recognize facial emotion and its development by the way of matching between own facial reactions to multisensory stimulation and facial expression of conspecifics. One question is how and when such a matching mechanism might influence facial expression processing. This issue will be addressed in studying healthy adults in using both behavioral and electrophysiological approaches. We will also investigate the role of matching self-generated expressions and expressions of others by studying patients with a deficit in both aspects of expressiveness and recognition of expressions; namely, schizophrenic patients. The second hypothesis is that non-visual sensory modalities may shape and constrain the matching process. Each modality has its own sensory processes and hedonic properties, and positive/negative feelings arise from these specific sensations. A direct consequence is that no modality will integrate the emotional environment in the way that corresponds to facial emotion categories (e.g., happiness, anger, disgust, fear, and sadness), at least before the learning of associations. Thus, multisensory integration not only promotes coupling processes between self-generated expressions and expressions from others, but they can also shape them according to the characteristics of every modality, and according to their development. We will test this hypothesis in infants. This project will include three main tasks. The first task will hold on healthy adults. The main objective will be to understand whether, how, and when the olfactory context influences facial emotion recognition. In experiment 1, we will study the influence of the olfactory context on facial emotion categories to assess whether the boundaries of these categories are flexible as a function of the emotional meaning of the odour. In experiment 2, we will study the potential early influence of the olfactory context on visual attention, using a visual search paradigm. Finally, in experiment 3, we will study further at which (temporal) level the olfactory context is integrated, using ERPs recordings. The second task will include infant’s studies. The purpose here will be to see whether infants can associate odour-induced feelings and facial expressions and, in case of positive answer to this first question, at which age. In experiment 4, we will study infants’ matching abilities between an odour and dynamic facial expressions. In experiment 5, we will study whether the olfactory context elicits an infant’s expectations for specific facial actions in neutral static expressions. Finally, in experiment 6, we will study whether infants are able to integrate the emotional states of their mother from stress-elicited body odours, and if they express expectations for specific facial information. Finally, in the third task, we will study schizophrenic patients, who are known to have both a deficit in facial expression recognition and a deficit in expressiveness (i.e., flat affect). The purpose of this task will be to assess whether the deficit of facial expressiveness in schizophrenia may influence both the categorical perception of facial expression and the contextual effect of olfactory stimulations. To test for this hypothesis, we will adapt experiment 1 and experiment 3 (task 1) to the study of schizophrenic patients. This approach, coupling cognitive psychology, developmental psychology, ethology and neuropsychology, will allow a better apprehension of processes going on during multisensory integration and facial emotion recognition/understanding by confronting human cognitive and emotional processes at different stages: either mature, under acquisition, or altered.