Autonomic nervous imbalance induced by obesity is directly related to altered brain glucose metabolism

International audienc

Chronic abdominal vagus stimulation increased brain metabolic connectivity, reduced striatal dopamine transporter and increased mid-brain serotonin transporter in obese miniature pigs

Abstract Background/objective Changes in brain metabolism has been investigated thoroughly during unilateral cervical chronic vagal stimulation in epileptic or depressive patients. Bilateral stimulation of the abdominal vagus (aVNS) has received less attention despite the reduction in body weight and an altered feeding behavior in obese animals that could be clinically relevant in obese individuals. Our study aims to examine the changes in brain glucose metabolism (CMRglu) induced by aVNS in obese adult miniature pigs. Dopamine (DAT) and serotonin transporters (SERT) were also quantified to further understand the molecular origins of the alterations in brain metabolism. Subjects/methods Pairs of stimulating electrodes were implanted during laparoscopy on both abdominal vagal trunks in 20 obese adult’s miniature pigs. Half of the animals were permanently stimulated while the remaining were sham stimulated. Two months after the onset of stimulation, dynamic 18FDG PET and 123I-ioflupane SPECT were performed. Food intake, resting energy expenditure and fat deposition were also assessed longitudinally. Results Food intake was halved and resting energy expenditure was increased by 60% in aVNS group compared to sham. The gain in body weight was also 38% less in aVNS group compared to sham. Brain metabolic connectivity increased between numerous structures including striatum, mid-brain, amygdala and hippocampus. On the contrary, increased CMRglu were restricted to the thalamus, the periaqueducal grey and the amygdala. DAT binding potential was decreased by about one third in the striatum while SERT was about doubled in the midbrain. Conclusions Our findings demonstrated that aVNS reduced weight gain as a consequence of diminished daily food intake and increased resting energy expenditure. These changes were associated with enhanced connectivity between several brain areas. A lower striatal DAT together with a doubled mid-brain SERT were likely causative for these changes

Altered brain processing after long-term artificial sweetener use

Altered brain processing after long-term artificial sweetener use. 25. European Congress on Obesity (ECO2018

Targeting brain network plasticity by chronic vagus nerve stimulation associated with weight loss

International audienc

Impact of long term supplement with artificial sweeteners on insulin dependent glucose uptake

Impact of long term supplement with artificial sweeteners on insulin dependent glucose uptake. 25. European Congress on Obesity (ECO2018

Obesity-associated alterations of glucose metabolism are ameliorated after chronic stimulation of abdominal vagus nerve

Obesity-associated alterations of glucose metabolism are ameliorated after chronic stimulation of abdominal vagus nerv

Obesity-associated alterations of glucose metabolism are ameliorated after chronic stimulation of abdominal vagus nerve

National audienc

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

National audienceIntroduction: 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, minipig