Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats

Acta Pharmacol Sin. 2012 Feb;33(2):194-200. doi: 10.1038/aps.2011.168.

Abstract

Aim: To validate the gubra DIO-rats as a useful animal model of human obesity.

Methods: The gubra diet-induced obesity (DIO) rat model was based on male Sprague-Dawley rats with ad libitum access to regular chow and a palatable diet rich in fat and sugar. To evaluate the versatility of the gubra DIO-rats as a valid model of human obesity syndrome, the efficacy of 2 weight loss compounds liraglutide and sibutramine with different mechanisms of action were examined in 7-month-old gubra DIO-rats. Liraglutide (200 μg/kg, sc) was administered bi-daily, and sibutramine (5 mg/kg, po) was administered once daily for 23 d.

Results: Both the compounds effectively reduced the food intake, body weight and total fat mass as measured by nuclear magnetic resonance. Whereas the 5-HT reuptake inhibitor/5-HT receptor agonist sibutramine reduced the intake of both chow and the gubra-diet, the GLP-1 analogue liraglutide predominantly reduced the intake of the highly palatable diet, indicating a shift in food preference. Sibutramine lowered the insulin sensitivity index, primarily via reductions in glucose-stimulated insulin secretion.

Conclusion: This animal model responds well to 2 weight loss compounds with different mechanisms of action. Moreover, the gubra DIO-rat can be particularly useful for the testing of compounds with potential effects on diet preference.

MeSH terms

  • Animals
  • Anti-Obesity Agents / pharmacology
  • Anti-Obesity Agents / therapeutic use*
  • Body Weight / drug effects*
  • Cyclobutanes / pharmacology
  • Cyclobutanes / therapeutic use*
  • Eating / drug effects*
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / pharmacology
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucose Tolerance Test
  • Insulin Resistance
  • Liraglutide
  • Male
  • Obesity / drug therapy*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anti-Obesity Agents
  • Cyclobutanes
  • Liraglutide
  • Glucagon-Like Peptide 1
  • sibutramine