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


CONCLUSIONS
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.
Gubra aps, Agern Allé 1, Hørsholm, Denmark. gh@gubra.dk
Gitte
G
Hansen
Jacob
J
Jelsing
Niels
N
Vrang
D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects*; D003503:Cyclobutanes / Q000494:pharmacology / Q000627:therapeutic use*; D004435:Eating / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D000069450:Liraglutide; D008297:Male; D009765:Obesity / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019440:Anti-Obesity Agents; D003503:Cyclobutanes; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; C058254:sibutramine