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

J Diabetes Res. 2015:2015:307285. doi: 10.1155/2015/307285. Epub 2015 Jul 2.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Anti-Obesity Agents / therapeutic use*
  • Biomarkers / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diet therapy
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / etiology*
  • Diabetic Neuropathies / complications
  • Diabetic Neuropathies / prevention & control*
  • Diet, Fat-Restricted*
  • Diet, High-Fat / adverse effects
  • Dietary Supplements*
  • Disease Models, Animal*
  • Enalapril / therapeutic use
  • Fish Oils / therapeutic use
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Neuralgia / complications
  • Neuralgia / prevention & control
  • Non-alcoholic Fatty Liver Disease / complications
  • Obesity / complications
  • Obesity / diet therapy
  • Obesity / drug therapy
  • Obesity / etiology*
  • Rats, Sprague-Dawley
  • Streptozocin / toxicity
  • Weight Loss / drug effects

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Obesity Agents
  • Biomarkers
  • Fish Oils
  • Hypoglycemic Agents
  • Menhaden oil
  • Streptozocin
  • Enalapril