35 - THE VAGUS MEDIATES GUT-BRAIN RESPONSE TO DUODENAL NUTRIENT ADMINISTRATION

Objectives: Obesity contributes significant disease burden worldwide, including diabetes, cardiovascular disease, and cancer. While bariatric surgery is the most effective and durable obesity treatment, the mechanisms underlying its effects remain unknown. Although neuro-hormonal mechanisms have been suspected to mediate at least some of the gut-brain axis changes following bariatric surgery, studies examining the intestine and its regionally specific post-gastric alterations to these signals remain unclear. Thus, as autonomic parasympathetics, primarily via the vagus nerve, contribute to food intake and body weight, these signaling mechanisms were examined in response to intestinal nutrient stimuli.

Methods: Vagus nerve recording was performed in mice using a platinum iridium wires technique following recovery from implantation of chronic duodenal feeding tubes in mice. Testing conditions and measurements were made under anesthesia during baseline, nutrient or vehicle solution delivery, and post-delivery. Solutions tested included water, 500mm glucose, 500mm glucose with an inhibitor of glucose absorption (phlorizin), and a hydrolyzed protein solution.

Results: Vagus nerve signaling was detectable from the duodenum and exhibited stable baseline activity without responding to osmotic pressure gradients. Duodenal delivered glucose and protein robustly increased vagus nerve signaling, but increased signaling was abolished during co-administration of glucose and phlorizin.

Conclusion: Gut-brain communication via the vagus nerve emanating from the duodenum is nutrient sensitive and easily measurable in mice. Examination of these signaling pathways may help elucidate how the nutrient signals from the intestine are altered when applied to obesity and bariatric surgery mouse models. Future studies will address quantifying the changes in neuroendocrine nutrient signals in health and obesity, with specific emphasis on identifying the changes associated with bariatric surgery and other gastrointestinal surgery.