TY - JOUR
T1 - Long-term characterization of the diet-induced obese and diet-resistant rat model
T2 - a polygenetic rat model mimicking the human obesity syndrome
AU - Madsen, Andreas Nygaard
AU - Hansen, Gitte
AU - Paulsen, Sarah Juel
AU - Lykkegaard, Kirsten
AU - Christensen, Mads Tang
AU - Hansen, Harald S.
AU - Levin, Barry E
AU - Larsen, Philip Just
AU - Knudsen, Lotte Bjerre
AU - Fosgerau, Keld
AU - Vrang, Niels
PY - 2010/9/1
Y1 - 2010/9/1
N2 - 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.
AB - 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.
KW - Analysis of Variance
KW - Animals
KW - Appetite Depressants
KW - Blood Glucose
KW - Cyclobutanes
KW - Diet
KW - Disease Models, Animal
KW - Eating
KW - Enzyme-Linked Immunosorbent Assay
KW - Feeding Behavior
KW - Glucagon-Like Peptide 1
KW - Insulin
KW - Insulin Resistance
KW - Leptin
KW - Metabolic Syndrome X
KW - Obesity
KW - Rats
KW - Rats, Sprague-Dawley
U2 - 10.1677/joe-10-0004
DO - 10.1677/joe-10-0004
M3 - Journal article
C2 - 20508079
SN - 0022-0795
VL - 206
SP - 287
EP - 296
JO - Journal of Endocrinology
JF - Journal of Endocrinology
IS - 3
ER -
