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

VL - 206

SP - 287

EP - 296

JO - Journal of Endocrinology

JF - Journal of Endocrinology

SN - 0022-0795

IS - 3

ER -