Abstract
Aims: Determine the effect of dietary oils enriched in different mono- or polyunsaturated fatty acids, i.e., olive oil (18 : 1, oleic acid), safflower oil (18 : 2 n-6, linoleic acid), flaxseed oil (18 : 3 n-3, alpha linolenic acid), evening primrose oil (18 : 3 n-6, gamma linolenic acid), or menhaden oil (20:5/22 : 6 n-3 eicosapentaenoic/docosahexaenoic acids), on vascular and neural complications in high-fat-fed low-dose streptozotocin-treated Sprague-Dawley rats, an animal model for late-stage type 2 diabetes. Materials and Methods: Rats were fed a high-fat diet (45% kcal as fat primarily derived from lard) for 8 weeks and then treated with a low dose of streptozotocin (30 mg/kg) in order to induce hyperglycemia. After an additional 8 (early intervention) or 20 (late intervention) weeks, the different groups of rats were fed diets with 1/2 of the kcal of fat derived from lard replaced by the different dietary oils. In addition, a control group fed a standard diet (4.25% kcal as fat) and a diabetic group maintained on the high-fat diet were maintained. The treatment period was approximately 16 weeks. The endpoints evaluated included vascular reactivity of epineurial arterioles, motor and sensory nerve conduction velocity, thermal and corneal sensitivity, and innervation of sensory nerves in the cornea and skin. Results: Our findings show that menhaden and flaxseed oil provided the greatest benefit for correcting peripheral nerve damage caused by diabetes, whereas enriching the high-fat diet with menhaden oil provided the most benefit to acetylcholine-mediated vascular relaxation of epineurial arterioles of the sciatic nerve. Enriching the diets with fatty acids derived from the other oils provided none to partial improvements. Conclusions: These studies imply that long-chain n-6 and n-3 polyunsaturated fatty acids could be an effective treatment for diabetic peripheral neuropathy with n-3 polyunsaturated fatty acids derived from fish oil being the most effective.
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Key Points
Peripheral neuropathy is the most common complication of diabetes affecting about 50% of patients. There is no treatment for peripheral neuropathy other than good glycemic control that is primarily only effective in patients with type 1 diabetes. It has been shown that treating diet-induced obese rats, an animal model of prediabetes, after vascular and nerve pathology had developed, with oils enriched in oleic acid or linoleic acid provided no improvement in vascular or neural function. Treating diet-induced obese rats with either γ- or α-linolenic acids, derived from evening primrose oil or flaxseed oil, respectively, provided a moderate benefit. The purpose of the present study was to gain a better understanding of the role of these same dietary lipids on vascular relaxation of arterioles that provide circulation to the sciatic nerve and peripheral neuropathy in an animal model of type 2 diabetes. In this study, Sprague-Dawley rats that were fed a high-fat diet for 8 weeks followed by a low dose of streptozotocin. After 8 or 20 weeks of nontreated hyperglycemia, these rats were fed a high-fat diet enriched in oleic acid (olive oil; 18 : 1, n-9), linoleic acid (safflower oil; 18 : 2, n-6), γ-linolenic acid (evening primrose oil; 18 : 3, n-6), α-linolenic acid (flaxseed oil; 18 : 3, n-3), or eicosapentaenoic/docosahexaenoic acids (menhaden oil; 20 : 5 and 22 : 6, n-3).
In this study, treating type 2 diabetic rats with a high-fat diet enriched with flaxseed oil partially improved vascular and neural functions. Flaxseed oil has also been shown to attenuate hepatic steatosis and insulin resistance in high-fat-fed mice through improving endoplasmic reticulum stress. In type 2 diabetic rats, flaxseed oil has been shown to alleviate protein glycation and inflammation in the liver Treating diabetic rats with flaxseed oil lead to an increase in the levels of eicosapentaenoic acid in serum and liver and a significant decrease in the n-6 to n-3 fatty acid ratio in serum. Overall, there was a trend for late intervention with flaxseed oil to be more efficacious in improving neural outcome measures and vascular relaxation to calcitonin gene-related peptide compared to early intervention. Future studies need to carefully evaluate the effect of treatment of diabetes on animal models as well as on human subjects with n-6 and n-3 polyunsaturated fatty acids on lipidomics and inflammatory mediators.