Team leaders: David Val-Laillet (DR INRA) & Gaëlle Boudry (CR INRA)
Metabolic syndrome and obesity are associated with neuro-behavioural modifications in relation to food hedonism and motivation, such as hyperphagia, snacking, cravings and addictive-like behaviours (Val-Laillet et al. 2015). Food intake is tightly regulated at the central level by two central systems/loops working in interaction (Berthoud 2002, Berthoud & Morrison 2008): the homeostatic system/loop, including the medulla and hypothalamus, which are integrative centres for signals from various peripheral origins; and the reward system/loop (brain reward circuit), notably composed of dopaminergic corticostriatal areas that are particularly responsive to high-fat and high-sugar foods (palatable food). The brain receives, combines and integrates exteroceptive information coming from external senses as well as the interoceptive information coming from the digestive system. Although extremely accurate, these complex interactions between homeostatic, energy-driven and non-homeostatic reward-driven processes and integration of extero- and interoceptive signals are compromised and degraded in metabolic syndrome or addictive habits (Ziauddeen et al. 2015). Yet, the exact mechanisms as well as the predisposing factors resulting in these changes in the homeostatic / reward systems are not understood.
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In the first approach, we plan to use animal models (pig and rodent) to investigate the temporal dynamic of intestinal and neurobehavioral alterations during chronic exposure to a deleterious nutritional environment. Study of this temporal dynamic includes nutritional changes occurring at the adult age as well as perinatal conditions. The relations between the gut and the brain will be first evaluated on a temporal basis to establish sequential relationships. Causal relationships and mechanisms will be tested using cell culture or gain-loss of function approaches. We aim to validate our results in human cohorts using non- or minimally invasive approaches when possible. Beside temporal relationships, this longitudinal approach will enable us to propose prevention strategies adjusted in terms of timing and target that could be initiated before the onset of pathological conditions in the general population and in at-risk subjects suffering from predisposing factors.
The second approach is clinical. Cohorts of patients hospitalized for different pathologies related to problematic eating habits (overweight, obesity, eating disorders, alcoholism) will be established to gather multifactorial data (e.g. via food questionnaires, psychological assessments, biological samples, functional brain imaging, etc.) and design relevant and efficient interventions for the target populations. The long-term goal is to use the same indicators than those discovered in the first strategy to predict the evolution of individual trajectories and orient the therapeutic approach (with the long-term goal of individualized medicine), and confirm the efficacy of intervention.
2- Impact of microbiota colonization on gut-brain development in infancy and long-term consequences on gut and metabolic homeostasis in adult with diet-induced obesity and metabolic syndrome.
3- Health promotion and reduction of the damages related to problematic consumption of alcohol in overweight/obese patients.
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