High-fat diet ingestion correlates with neuropathy in the duodenum myenteric plexus of obese mice with symptoms of type 2 diabetes

Abstract

Obesity and type 2 diabetes are increasing in prevalence at an alarming rate in developed and developing nations and over 50 % of patients with prolonged stages of disease experience forms of autonomic neuropathy. These patients have symptoms indicating disrupted enteric nervous system function including gastric discomfort, gastroparesis and intestinal dysmotility. Previous assessments have examined enteric neuronal injury within either type 1 diabetic or transgenic type 2 diabetic context. This study aims to assess damage to myenteric neurons within the duodenum of high-fat diet ingesting mice experiencing symptoms of type 2 diabetes, as this disease context is most parallel to the human condition and disrupted duodenal motility underlies negative gastrointestinal symptoms. Mice fed a high-fat diet developed symptoms of obesity and diabetes by 4 weeks. After 8 weeks, the total number of duodenal myenteric neurons and the synaptophysin density index were reduced and transmission electron microscopy showed axonal swelling and loss of neurofilaments and microtubules, suggesting compromised neuronal health. High-fat diet ingestion correlated with a loss of neurons expressing VIP and nNOS but did not affect the expression of ChAT, substance P, calbindin and CGRP. These results correlate high-fat diet ingestion, obesity and type 2 diabetes symptoms with a loss of duodenal neurons, biasing towards those with inhibitory nature. This pathology may underlie dysmotility and other negative GI symptoms experienced by human type 2 diabetic and obese patients.

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Acknowledgements

This study was funded by the University of Idaho WWAMI Medical Education program, Idaho INBRE (NIH Grants: P20 RR016454 and P20 GM103408) and a University of Idaho Start-Up fund. The authors would like to acknowledge Savannah Patterson and Joshua Cady for their help with staining and quantification procedures.

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Correspondence to Onesmo Balemba.

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Stenkamp-Strahm, C.M., Kappmeyer, A.J., Schmalz, J.T. et al. High-fat diet ingestion correlates with neuropathy in the duodenum myenteric plexus of obese mice with symptoms of type 2 diabetes. Cell Tissue Res 354, 381–394 (2013). https://doi.org/10.1007/s00441-013-1681-z

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Keywords

  • Myenteric plexus
  • Nerve injury
  • Type 2 diabetes
  • Vasoactive intestinal peptide
  • Nitric oxide synthase