Molecular mechanisms of enteric neuropathies in high-fat diet feeding and diabetes

Background: Obesity and diabetes are associated with altered gastrointestinal function and with the development of abdominal pain, nausea, diarrhea, and constipation among other symptoms. The enteric nervous system (ENS) regulates gastrointestinal motility. Enteric neuropathies defined as damage or loss of enteric neurons can lead to motility disorders. Purpose: Here, we review the molecular mechanisms that drive enteric neurodegeneration in diabetes and obesity, including signaling pathways leading to neuronal cell death, oxidative stress, and microbiota alteration. We also highlight potential approaches to treat enteric neuropathies including antioxidant therapy to prevent oxidative stress-induced damage and the use of stem cells.