Omega-3 Polyunsaturated Fatty Acids Effect on Neuropathy of the Peripheral Nervous System in Dietary Obese Rats: Is the Source of These Fatty Acids Important for Outcome?

Abstract

Objective: To answer the question what is the best source or composition of omega-3 polyunsaturated fatty acids (PUFA) that will provide the most favorable and safe outcome for peripheral neuropathy (PN) in an animal model of obesity? Traditionally encapsulated fish oil is the primary source of omega-3 PUFA as a nutritional supplement. However, other sources exist that could be a better environmental, safety, and/or economic choice.

Methods: Male Sprague Dawley rats 12 weeks of age were fed a 45% kcal diet to induce obesity and model pre-diabetes. Early and late intervention protocols were used to determine the ability of omega-3 PUFA derived from menhaden (fish) oil, krill oil, algal oils, or ethyl esters to slow the progression or reverse PN associated with pre-diabetes by examining multiple endpoints of sensory nerve function, morphometry and vascular reactivity. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the primary omega-3 PUFA, and a combination exist in fish and krill oil. However, algal oils and ethyl esters are available as EPA, DHA, or EPA & DHA and each were used in this study.

Results: We report that multiple sources of omega-3 PUFA are a proactive treatment for PN that occurs with pre-diabetes including improvement in sensory nerve conduction velocity, thermal nociception and cornea sensitivity and corneal nerve fiber length. Improvement in vascular reactivity of epineurial arterioles of the sciatic nerve was observed. We also report that EPA and DHA had different outcomes for these endpoints.

Conclusion: We confirm that omega-3 PUFA are an effective treatment to prevent and reverse PN associated with obesity and pre-diabetes. Additional studies will be needed to definitively determine what would be the best and most consistent source of this important nutritional supplement from an environmental and economical viewpoint.

Keywords: fish oil; obesity; omega-3 polyunsaturated fatty acids; peripheral neuropathy.

Figure 1

Effect of dietary intervention with menhaden oil, krill oil, and oils from algae that produce EPA, DHA or the combination of EPA/DHA on vascular relaxation by acetylcholine in epineurial arterioles of the sciatic nerve in diet-induced obese/pre-diabetic Sprague-Dawley rats. Pressurized arterioles (40 mm Hg and ranging from 60–100 µm luminal diameters) were constricted with phenylephrine (30–50%) and incremental doses of acetylcholine were added to the bathing solution while recording steady state vessel diameter. The number of rats in each group ranged from 10–14. Data are presented as the mean of % relaxation ± S.E.M. *p < 0.05 compared to control rats.

Figure 2

Effect of dietary intervention with menhaden oil, and ethyl esters of EPA, DHA or the combination of EPA/DHA on vascular relaxation by acetylcholine in epineurial arterioles of the sciatic nerve in diet-induced obese/pre-diabetic Sprague-Dawley rats. Pressurized arterioles (40 mm Hg and ranging from 60–100 µm luminal diameters) were constricted with phenylephrine (30–50%) and incremental doses of acetylcholine were added to the bathing solution while recording steady state vessel diameter. The number of rats in each group ranged from 10–14. Data are presented as the mean of % relaxation ± S.E.M. *p < 0.05 compared to control rats.

Figure 3

Effect of dietary intervention with menhaden oil, krill oil, and oils from algae that produce EPA, DHA or the combination of EPA/DHA on vascular relaxation by CGRP in epineurial arterioles of the sciatic nerve in diet-induced obese/pre-diabetic Sprague-Dawley rats. Pressurized arterioles (40 mm Hg and ranging from 60–100 µm luminal diameters) were constricted with phenylephrine (30–50%) and incremental doses of CGRP were added to the bathing solution while recording steady state vessel diameter. The number of rats in each group ranged from 10–14. Data are presented as the mean of % relaxation ± S.E.M. *p < 0.05 compared to control rats.

Figure 4

Effect of dietary intervention with menhaden oil, and ethyl esters of EPA, DHA or the combination of EPA/DHA on vascular relaxation by CGRP in epineurial arterioles of the sciatic nerve in diet-induced obese/pre-diabetic Sprague-Dawley rats. Pressurized arterioles (40 mm Hg and ranging from 60–100 µm luminal diameters) were constricted with phenylephrine (30–50%) and incremental doses of CGRP were added to the bathing solution while recording steady state vessel diameter. The number of rats in each group ranged from 10–14. Data are presented as the mean of % relaxation ± S.E.M. *p < 0.05 compared to control rats.