A High Fat Diet and the Little Brain in the Gut: Lessons from a Mouse Model

Yvonne Nyavor, Biology/Neuroscience

First Place: Graduate Disciplinary Research Presentation

Abstract: Diabetic patients suffer from complications including neuropathy, and gastrointestinal neuropathy is considered to be the major underlying cause of negative gastrointestinal symptoms including, constipation, dysmotility, diarrhea and gastroparesis. A high fat diet (HFD) has been shown to damage myenteric inhibitory motor neurons in the duodenum, but its effects on inhibitory junction potentials (IJPs) and motility are unknown. We hypothesized that a high fat diet causes damage to inhibitory myenteric motor neurons in both upper and lower parts of the gut of mice. This damage may then induce a decline in IJPs, resulting in intestinal dysmotility. We used a high fat diet induced model of obesity and Type 2 Diabetes in mice. We found male mice on a HFD developed symptoms of obesity and Diabetes while female mice on a HFD did not. However, gastrointestinal motility assays revealed impaired motility in the duodenum of both male and female HFD fed mice. Motility in the distal colon was affect only in male mice fed a HFD, but IJPs were highly reduced in both male and female mice on a high fat diet. These results suggest that a high fat diet affects the nervous system in both the fore and hind gut, and the resulting nerve damage may develop independently of Obesity and Type 2 Diabetes. Future work will characterize the extent of this damage and test novel therapies to protect enteric neurons from the effects of a high fat diet.