Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome.
The availability of useful animal models reflecting the human obesity syndrome is crucial in the search for novel compounds for the pharmacological treatment of obesity. In the current study, we have performed an extensive characterization of the obesity syndrome in a polygenetic animal model, namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization including blood biochemistry and glucose homeostasis was examined at 2, 3, 6, and 9 months of age. Furthermore, in 6-month-old HE-fed DIO rats, the anti-obesity effects of liraglutide and sibutramine were examined in a 28-day study. Only HE-fed DIO rats developed visceral obesity, hyperleptinemia, hyperinsulinemia, and dyslipidemia, and showed a worsening of glucose tolerance over time. In line with the hyperlipidemic profile, a severe hepatic fat infiltration was observed in DIO rats at 6 months of age. The effects of liraglutide and sibutramine were tested in 6-month-old DIO rats. Both compounds effectively reduced food intake and body weight in DIO rats. Liraglutide furthermore improved glucose tolerance when compared with sibutramine. Our data highlights the usefulness of a polygenetic animal model for screening of compounds affecting food intake, body weight, and glucose homeostasis. Furthermore, the results underscore the effectiveness of GLP-1 mimetics both as anti-diabetes and anti-obesity agents.
Rheoscience A/S, Rødovre 2610, Copenhagen, Denmark.
Andreas Nygaard
AN
Madsen
Gitte
G
Hansen
Sarah Juel
SJ
Paulsen
Kirsten
K
Lykkegaard
Mads
M
Tang-Christensen
Harald S
HS
Hansen
Barry E
BE
Levin
Philip Just
PJ
Larsen
Lotte Bjerre
LB
Knudsen
Keld
K
Fosgerau
Niels
N
Vrang
D000704:Analysis of Variance; D000818:Animals; D001067:Appetite Depressants / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D003503:Cyclobutanes / Q000627:therapeutic use; D004032:Diet; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005247:Feeding Behavior / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D000069450:Liraglutide; D024821:Metabolic Syndrome / Q000378:metabolism / Q000503:physiopathology*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001067:Appetite Depressants; D001786:Blood Glucose; D003503:Cyclobutanes; D007328:Insulin; D020738:Leptin; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; C058254:sibutramine