Abstract

In this study, we wanted to extend our investigation of the efficacy of fish oil with or without salsalate on vascular and neural complications using a type 2 diabetic rat model. Four weeks after the onset of hyperglycemia, diabetic rats were treated via the diet with 3 different amounts of menhaden oil with or without salsalate for 12 weeks. Afterwards, vascular reactivity of epineurial arterioles and neuropathy-related endpoints were examined. The addition of salsalate to high-fat diets enriched with 10% or 25% kcal of menhaden oil protected vascular reactivity to acetylcholine and calcium gene-related peptide, motor and sensory nerve conduction velocity, thermal nociception, intraepidermal nerve fiber density, and cornea sensitivity to a greater extent than 10% or 25% menhaden oil alone. Vascular and neural function was maximally protected with diet containing 45% kcal as menhaden oil, and adding salsalate did not provide any additional benefit. Salsalate alone in the high-fat diet of diabetic rats provided minimal protection/improvement of vascular and neural dysfunction. These studies imply that dietary salsalate in combination with lower amounts of menhaden oil can provide greater benefit toward diabetes-induced vascular and neural impairment than menhaden oil alone.

Highlights

  • Peripheral neuropathy is one of the most common complications of diabetes and has been reported to affect about 50% of the diabetic population, and up to 30% of the population reported to be prediabetic with insulin resistance [1, 2]

  • Serum triglyceride levels were significantly increased in the untreated diabetic rats and diabetic rats treated with menhaden oil compared to control rats

  • Serum triglyceride levels in diabetic rats treated with salsalate were higher than those observed in control rats, but the comparison was not statistically different

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Summary

Introduction

Peripheral neuropathy is one of the most common complications of diabetes and has been reported to affect about 50% of the diabetic population, and up to 30% of the population reported to be prediabetic with insulin resistance [1, 2]. We have demonstrated that increasing the dietary content of fish oil alone or in combination is an effective treatment for vascular and neural complications in diabetic rodents [3, 4]. We have shown that cotreatment of type 1 diabetic mice with menhaden (fish) oil and salsalate is more effective toward neuropathy than menhaden oil alone and that circulating resolvin D1 levels are increased when salsalate is combined with menhaden oil [5]. We have demonstrated that treating either type 1 or type 2 diabetic mice with daily injections of resolvin E1 or D1, metabolites of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively, most abundant omega-3 polyunsaturated fatty acids found in fish oil, improves peripheral neuropathy [6, 7]

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