Neuropathy, a debilitating complication of diabetes, has primarily been attributed to poor glycemic control, but has recently been associated with obesity and the metabolic syndrome in nondiabetic individuals. A robust body of evidence indicates that a high-fat diet can induce signs of neuropathy in mice but the pathogenesis of high fat diet-induced neuropathy remains unknown.
PURPOSE: To determine if neuronal inflammation is a potential initiating mechanism for the development of mechanical hypersensitivity and nerve fiber changes (signs of neuropathy) in high fat fed mice. METHODS: Male C57Bl/6 mice were randomized to a standard (Std, 15% kcal from fat) or high fat diet (HF, 54% kcal from fat) for 2, 4, or 8 wks (n = 11-12 per group). 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-α, MIP-1α, GMCSF, RANTES) were quantified using a Multiplex ELISA and normalized to total protein. Neuropathy was characterized by the von Frey test for mechanical sensitivity at wk 0 and every other week thereafter. Hindpaw foot pad skin was harvested at end study and used to quantify intraepidermal nerve fiber density (IENFD) and pain-sensing (TrkA) nerve fibers via immunohistochemistry. RESULTS: After 8 wks, HF had greater bodyweight (33.3 ± 1.0 vs. 26.7 ± 0.5 g, p < 0.001), fasting blood glucose (160.3 ± 9.4 vs. 138.5 ± 3.4 mg/dl, p < 0.05) and insulin (3.58 ± 0.46 vs. 0.82 ± 0.14 ng/ml, p < 0.001) compared to Std. IL-1α, RANTES and IL-5 were higher in HF compared to Std after 2 wks and 4 wks, respectively (IL-1α: 4.8 ± 1.3 vs. 2.9 ± 0.6 pg/mg, p < 0.05; RANTES: 19.6 ± 2.2 vs. 13.3 ± 1.2 pg/mg p < 0.05; IL-5: 5.8 ± 0.7 vs. 3.1 ± 0.5 pg/mg, p < 0.05 ). IENFD and TrkA fiber density were also higher in HF vs. Std after 4 wks (IENFD: 39.4 ± 1.2 vs. 32.2 ± 1.3 fibers/mm, p < 0.001; TrkA: 30.4 ± 1.8 vs. 22.4 ± 1.3 fibers/mm). There were no significant differences in hindpaw sensitivity for Std vs. HF at any time point. CONCLUSION: Increased inflammatory mediators preceded and accompanied an increase in a specific population of pain sensing nerve fibers (TrkA) in the hindpaw footpad of high fat fed mice. Diets high in fat may increase neuronal inflammation and initiate nerve fiber changes responsible for painful neuropathy in nondiabetic and diabetic individuals.
|Advisor:||Guilford, Brianne L.|
|Commitee:||Witt, Ken A., Wooten, Joshua S.|
|School:||Southern Illinois University at Edwardsville|
|Department:||Kinesiology and Health Education|
|School Location:||United States -- Illinois|
|Source:||MAI 56/04M(E), Masters Abstracts International|
|Keywords:||High fat, Inflammation, Neuronal inflammation, Neuropathy, Obesity|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be