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

Acta Pharmacologica Sinica 33:194–200, 2012

Hansen G, Jelsing J, Vrang N.

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 two weight loss compounds, liraglutide and sibutramine, with different mechanisms of action, were examined in 7-month-old Gubra DIO-rats. Liraglutide (200 μg/kg, subcutaneous) was administered twice daily, and sibutramine (5 mg/kg, oral) was administered once daily for 23 days.

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

Conclusion: The Gubra DIO-rat model responds well to two weight loss compounds with distinct mechanisms of action. Moreover, this model can be particularly useful for testing compounds with potential effects on diet preference.

Subjects
Therapeutic AreaDIO ratTargetCompoundMethod/EndpointBody compositionBody weightObesityGLP-1 receptorOral glucose tolerance test (OGTT)Real-time food intake/activity analysisLiraglutideSibutramine

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