Rat Models of Diet-Induced Obesity and High Fat/Low Dose Streptozotocin Type 2 Diabetes: Effect of Reversal of High Fat Diet Compared to Treatment with Enalapril or Menhaden Oil on Glucose Utilization and Neuropathic Endpoints.

Amey Holmes,Lawrence J Coppey,Mark A Yorek,Eric P Davidson

doi:10.1155/2015/307285

Abstract

We examined whether reversal of high fat diet, stimulating weight loss, compared to two treatments previously shown to have beneficial effects, could improve glucose utilization and peripheral neuropathy in animal models of obesity and type 2 diabetes. Rats were fed a high fat diet and treated with a low dose of streptozotocin to create models of diet induced obesity or type 2 diabetes, respectively. Afterwards, rats were transferred to a normal diet or treated with enalapril or dietary enrichment with menhaden oil for 12 weeks. Obesity and to a greater extent type 2 diabetes were associated with impaired glucose utilization and peripheral neuropathy. Placing obese rats on a normal diet improved glucose utilization. Steatosis but not peripheral neuropathy was improved after placing obese or diabetic rats on a normal diet. Treating obese and diabetic rats with enalapril or a menhaden oil enriched diet generally improved peripheral neuropathy endpoints. In summary, dietary improvement with weight loss in obese or type 2 diabetic rats was not sufficient to correct peripheral neuropathy. These results further stress the need for discovery of a comprehensive treatment for peripheral neuropathy.

Highlights

The goal of these studies was to determine whether replacing the high fat diet with a normal diet would improve glucose utilization and/or peripheral neuropathy in diet induced obese or type 2 diabetic rats
We previously demonstrated that diet induced obese rats develop whole body insulin resistance and sensory neuropathy associated with reduced sensory nerve conduction velocity, thermal hypoalgesia, and decreased intraepidermal nerve fiber density in the skin of the hindpaw [18]
Diabetic rats placed on the normal diet or treated with enalapril trended to weigh less than the untreated diabetic rats

Summary

Introduction

The goal of these studies was to determine whether replacing the high fat diet with a normal diet would improve glucose utilization and/or peripheral neuropathy in diet induced obese or type 2 diabetic rats. We previously demonstrated that diet induced obese rats develop whole body insulin resistance and sensory neuropathy associated with reduced sensory nerve conduction velocity, thermal hypoalgesia, and decreased intraepidermal nerve fiber density in the skin of the hindpaw [18]. Treating diet induced obese rats with a low dose of streptozotocin damages insulin producing β-cells so that hyperglycemia develops even though insulin levels are similar or even higher than in normal fed control rats [19, 21]. The diabetes in these rats is analogous to the development of human type 2 diabetes when

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