Impact d'une exposition périnatale au sucre et au gras via le régime maternel sur le comportement, les adaptations, métaboliques et cérébrales de miniporcs Yucatan

Introduction: A lot of evidences defend the existence of a relationship between a Western diet and the increase of obesity prevalence (OMS, 2011). Particularly, the quality of early nutrition has a long-term impact on the offspring’s phenotype and health status (Barker, 1989). The aim of our study was to explore in the Yucatan minipig model the impact of the maternal diet (High Fat Fructose diet, HFF versus standard diet, STD) during pregnancy and lactation on the cognitive and hedonic functions of the offspring at the adult age, through behavioural assessments and brain imaging, combined with metabolic and physiological explorations. A challenge with an obesogenic diet was then performed to assess its effects on eating behaviour, weight gain and blood parameters.Material & methods: Learning and memory performances were tested using the holeboard discrimination task, with a palatable food reward (M&M’s®), and an Alley maze test, independent from food reward. Eating behaviour was explored with a two-choice feed test and an operant conditioning test with progressive ratio. In parallel, the brain basal glucose metabolism was investigated using Positron Emission Tomography (PET) and the dopaminergic brain reward system (in particular the striatum) was explored using DAT-scan imaging. Biologic samples were collected for blood profiles and analysis of the gut microbiota activity (FFA).Results: We showed that early nutrition could indirectly impact cognitive performances, modulating the emotional status in a high-anxiogenic/low-motivating (maze) situation, but not in low-anxiogenic/high-motivating situation (holeboard). As a matter of fact, STD better succeeded in the maze, whereas no difference appeared during the holeboard test. During the feeding tests, HFF showed a tendency to eat more than STD group. Brain sub-activations in the anterior prefrontal cortex and accumbens nucleus, as well as impairment of the striatal dopaminergic system were observed, which may explain eating behavior differences between HFF and STD. On the other hand, HFF presented better lipids profiles than STD. After an obesogenic challenge, we surprisingly observed that STD ate and gained more weight than HFF, while HFF inflammatory status was higher than STD. Conclusion: All these results suggest that HFF maternal western diet had a deleterious impact on the neurocognitive functions, in a high stressful situation, of the offspring and modulated its responses to an obesogenic dietary challenge.Key words: nutritional imprinting, behavior, brain, reward system, memory, learning, minipigs