NEUROPLASTICITY OF ENTERIC NERVOUS SYSTEM IN ANIMAL MODEL OF OBESITY

An altered functional innervation of the intestine by the enteric nervous system has been demonstrated in various obese animal models. Pathological changes in histological features confirmneuronal plasticity in obesity conditions. Since we have already assessed central nervous system alterations in obese animals, the current study will aim at providing the long-term peripheric effects of obesity on the enteric nervous system in obese rats.Here, we investigated the potential obesity-related alterations in the small and large intestines. We studied rats with obesity induced by diet after long-term exposure to a high-fat diet com-pared with animals fed a standard diet. We examined whether consuming this diet induced a temporal progression of changes in glial cells and neurons along the innervation of the gut using different markers through immunohistochemical and immunochemical techniques to visualize the morphological and functional modulations of the heterogeneous neuronal population of the gut wall. Obesity developed after five weeks of a high-fat diet.Concerning the results in obese conditions, myenteric neuronsshowed a reduction in neuronal marker staining, suggesting a degeneration associated with obesity. An increased glial reactivity was found in the jejunum of obese rats, which pointed out a suffering condition of nervous tissue that leads astrocytes to pro-tect the neuronal microenvironment. On the contrary, a reduced expression of the glial fibrillary acidic protein was found in the ileum and the distal colon of treated rats suggesting a neurona ldegeneration related to lipotoxicity. Moreover, the network of vesicular acetylcholine transporter was more evident in the intestine of obese rats than in lean controls to counteract cholinergichypofunction of motoneurons in dysmetabolic conditions. Finally,we found fewer nitrergic neurons in the duodenum and the jejunum of obese animals, and we speculate that a hypercaloric diet reduced inhibitory neuromuscular transmission. In conclu-sion, consuming a high-fat hypercaloric diet makes a temporalprogression of changes in glial cells and neurons along the inner-vation of the gut of obese animal models, causing several gas-trointestinal alterations. Damages to the enteric glia could also affect the integrity of enteric neurons, increase the network of cholinergic neurons, and decrease nitrergic neurons. These findings suggest that obesity induces myenteric neurodegeneration.