Dissertation/Thesis Abstract

Neuronal Inflammation: A Potential Contributing Mechanism to High Fat Diet-Induced Neuropathy
by Umbaugh, David S., M.S., Southern Illinois University at Edwardsville, 2017, 40; 10276211
Abstract (Summary)

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.

Indexing (document details)
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
Source Type: DISSERTATION
Subjects: Biology, Kinesiology
Keywords: High fat, Inflammation, Neuronal inflammation, Neuropathy, Obesity
Publication Number: 10276211
ISBN: 9781369838121
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