Omega-3-Fatty Acids Hold Therapeutic Potential for the Prevention of "Metabolic" Neuropathy

Abstract

Diabetic neuropathy is one of the most common complications of diabetes, affecting most diabetic patients. Overweight humans display manifestations of diabetic neuropathy before developing overt diabetes. Mice fed a high fat diet exhibit signs of neuropathy including mechanical hindpaw hypersensitivity and neuronal inflammation, suggesting fat diet-induced inflammation may play a role in the development of neuropathy. Omega-3 (n-3) fatty acids have anti-inflammatory properties and may hold therapeutic potential as a preventative treatment for prediabetic and diabetic patients at risk for neuropathy. PURPOSE: We investigated the impact of diet composition on signs of neuropathy. We hypothesized that a diet rich in n-3 fatty acids would attenuate hindpaw hypersensitivity during prolonged feeding of a high fat diet. METHODS: C57BL/6 mice were randomized into four diet groups (n = 12/group) for 32 weeks: 10% low fat-fish oil (10%FO), 41% high fat-fish oil (41%FO), 10% low fat-lard (10%L), or 41% high fat-lard (41%L). Neuropathy was characterized at baseline and every other week thereafter using the von Frey behavioral test for hindpaw mechanical sensitivity. A glucose tolerance test was performed at end study, and total area under the curve (AUC) was calculated using the trapezoidal method. Upon sacrifice hindpaw footpads were dissected and immunohistochemistry was performed to quantify intraepidermal nerve fiber density (IENFD) and tyrosine kinase-A (TrkA) specific nerve fibers. RESULTS: At the end of the study, body weight was greater in 41%L compared to all other groups. Body weight was a higher in 41%L compared to 10%FO and 41%FO. Although percent paw withdrawal was greater in 41%L compared to 41%FO and 10%FO, there were no significant differences for 10% vs. 41% for fish oil or lard. Fasting glucose and glucose AUC were significantly greater in 41%L compared to 10%FO. Additionally, glucose AUC was greater in 41%FO compared to 10%FO. There were no significant differences in IENF or TrkA nerve fiber density. CONCLUSION: A 41%L diet induced signs of neuropathy including hindpaw hypersensitivity, whereas a fish oil diet was protective against hindpaw hypersensitivity. Moreover, n-3 acids may hold therapeutic potential for neuropathy prevention in nondiabetic and diabetic patients