Article Title



David S. Umbaugh, Jane C. Maciejewski, & Brianne L. Guilford Southern Illinois University Edwardsville, Edwardsville, Illinois; e-mail: dumbaug@siue.edu

Diabetic neuropathy is a common complication of diabetes that reduces the quality of life for millions of Americans. Overweight humans with dyslipidemia develop neuropathy before developing overt diabetes. In addition, recent evidence indicates a high-fat diet induces signs of neuropathy in rodents and may contribute to the development of neuropathy in pre-diabetic and/or diabetic humans, but mechanisms underlying high-fat diet induced neuropathy have not been elucidated. PURPOSE: The overall aim was to identify neuronal inflammation as a potential mechanism underlying the pathogenesis of high-fat diet-induced neuropathy. These experiments tested the hypothesis that a HF diet induces neuronal inflammation. METHODS: Male C57Bl/6 mice were randomized to two groups and fed a standard (Std) or high-fat diet (HF) for 8 weeks. The lumbar dorsal root ganglia were harvested and inflammatory mediators (IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-17, MCP-1, IFN-γ, TNF-γ, MIP-1α, GMCSF, and RANTES) were analyzed using a Multiplex ELISA. Neuropathy was characterized using the von Frey test for hindpaw mechanical sensitivity at baseline and every other week thereafter. RESULTS: At the end of the 8 wk intervention, the HF fed mice had significantly higher bodyweight and fasting blood glucose levels. Hindpaw mechanical sensitivity was not significantly different between groups at any timepoint. However, hindpaw mechanical sensitivity trended toward an increase from baseline (56.3 ± 0.05%) to wk 8 (70.8 ± 0.06%) in HF (p = 0.055) compared to Std (baseline: 56.9 ± 0.05% ; wk 8 : 61.4 ± 0.07%). MCP-1 was significantly higher in HF compared to Std after the 8 wk intervention. There were no other significant differences in inflammatory mediators between the groups. CONCLUSION: Although hindpaw mechanical hypersensitivity is characteristic of HF feeding in mice, the mild increase in hindpaw mechanical sensitivity did not reach statistical significance in this cohort. The HF fed mice exhibited elevated MCP-1 levels compared to Std fed mice which is suggestive of diet-induced inflammation. MCP-1 is understood to play a crucial role in the recruitment of inflammatory mediators, which suggests diet-induced inflammation may play a role in establishing neuropathy.

Funding provided by Southern Illinois University Edwardsville Seed Grants for Transitional and Exploratory Projects.

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