Why Your Gut May be Working Against You: Gut Derived Molecules Cause Dysmotility and Neuropathy in High Fat Fed Mice

Additional Funding Sources

The project described was supported by a 2017-2018 STEM Undergraduate Research Grant from the Higher Education Research Council.

Presentation Date

7-2018

Abstract

Type 2 diabetes (T2D) is a prevalent disease in the United States, affecting 21.9 million people. Recent studies have shown the development of gastrointestinal dysmotility and neuropathy before the onset of T2D, and ileocecal supernatants from high fat (HF) fed mice caused dysmotility and neuropathy ex vivo. However, the specific cause of dysmotility and neuropathy is still not known. We hypothesized that fractions from HF ileocecal supernatants would cause dysmotility and neuropathy. High Performance Liquid Chromatography (HPLC) was used to separate supernatants into aqueous (water) and methanolic fractions which were tested on mice intestinal muscularis tissue. Contractions of the tissue samples were counted, and immunohistochemistry and imaging used to determine if these fractions caused neuropathy. Water fractions from HF mice caused a significant decrease in muscularis contractions after 24 hours; water fractions of standard chow fed (SC) mice and methanolic fractions of HF and SC mice did not significantly induce dysmotility. We predict that the HF water fractions will also cause neuropathy. These results suggest a molecule(s) in these fractions is causing dysmotility and possibly neuropathy. Further study can reveal the molecule (s) and lead to potential biomarkers and treatments for dysmotility and neuropathy before T2D symptoms.

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Why Your Gut May be Working Against You: Gut Derived Molecules Cause Dysmotility and Neuropathy in High Fat Fed Mice

Type 2 diabetes (T2D) is a prevalent disease in the United States, affecting 21.9 million people. Recent studies have shown the development of gastrointestinal dysmotility and neuropathy before the onset of T2D, and ileocecal supernatants from high fat (HF) fed mice caused dysmotility and neuropathy ex vivo. However, the specific cause of dysmotility and neuropathy is still not known. We hypothesized that fractions from HF ileocecal supernatants would cause dysmotility and neuropathy. High Performance Liquid Chromatography (HPLC) was used to separate supernatants into aqueous (water) and methanolic fractions which were tested on mice intestinal muscularis tissue. Contractions of the tissue samples were counted, and immunohistochemistry and imaging used to determine if these fractions caused neuropathy. Water fractions from HF mice caused a significant decrease in muscularis contractions after 24 hours; water fractions of standard chow fed (SC) mice and methanolic fractions of HF and SC mice did not significantly induce dysmotility. We predict that the HF water fractions will also cause neuropathy. These results suggest a molecule(s) in these fractions is causing dysmotility and possibly neuropathy. Further study can reveal the molecule (s) and lead to potential biomarkers and treatments for dysmotility and neuropathy before T2D symptoms.