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

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.

Figure 1

Effect of treatment of diet induced obese rats (a) and high fat fed/low dose streptozotocin type 2 diabetic rats (b) with normal diet, enalapril, or menhaden oil on glucose tolerance. Glucose tolerance was determined as described in Section 2. Data are presented as the mean ± S.E.M. in mg/dl. The number of rats in each group was the same as shown in Table 1. Control rats (C), diet induced obese rats (HF), diabetic rats (HF STZ), and rats returned to a normal diet or treated with enalapril or placed on a menhaden oil enriched diet designated as Rev, Enal, or MO, respectively.