Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome

Andreas Nygaard Madsen; Gitte Hansen; Sarah Juel Paulsen; Kirsten Lykkegaard; Mads Tang Christensen; Harald S. Hansen; Barry E Levin; Philip Just Larsen; Lotte Bjerre Knudsen; Keld Fosgerau; Niels Vrang

doi:10.1677/joe-10-0004

Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome

Andreas Nygaard Madsen, Gitte Hansen, Sarah Juel Paulsen, Kirsten Lykkegaard, Mads Tang Christensen, Harald S. Hansen, Barry E Levin, Philip Just Larsen, Lotte Bjerre Knudsen, Keld Fosgerau, Niels Vrang

108 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Endocrinology
Volume	206
Issue number	3
Pages (from-to)	287-96
Number of pages	10
ISSN	0022-0795
DOIs	https://doi.org/10.1677/joe-10-0004
Publication status	Published - 1 Sept 2010

Keywords

Analysis of Variance
Animals
Appetite Depressants
Blood Glucose
Cyclobutanes
Diet
Disease Models, Animal
Eating
Enzyme-Linked Immunosorbent Assay
Feeding Behavior
Glucagon-Like Peptide 1
Insulin
Insulin Resistance
Leptin
Metabolic Syndrome X
Obesity
Rats
Rats, Sprague-Dawley

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1677/joe-10-0004

https://joe.bioscientifica.com/downloadpdf/journals/joe/206/3/287.pdf

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Madsen, A. N., Hansen, G., Paulsen, S. J., Lykkegaard, K., Christensen, M. T., Hansen, H. S., Levin, B. E., Larsen, P. J., Knudsen, L. B., Fosgerau, K., & Vrang, N. (2010). Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome. Journal of Endocrinology, 206(3), 287-96. https://doi.org/10.1677/joe-10-0004

Long-term characterization of the diet-induced obese and diet-resistant rat model : a polygenetic rat model mimicking the human obesity syndrome. / Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel et al.

In: Journal of Endocrinology, Vol. 206, No. 3, 01.09.2010, p. 287-96.

Research output: Contribution to journal › Journal article › Research › peer-review

Madsen, AN, Hansen, G, Paulsen, SJ, Lykkegaard, K, Christensen, MT, Hansen, HS, Levin, BE, Larsen, PJ, Knudsen, LB, Fosgerau, K & Vrang, N 2010, 'Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome', Journal of Endocrinology, vol. 206, no. 3, pp. 287-96. https://doi.org/10.1677/joe-10-0004

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abstract = "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.",

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AU - Lykkegaard, Kirsten

AU - Christensen, Mads Tang

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AU - Levin, Barry E

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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.

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KW - Feeding Behavior

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KW - Metabolic Syndrome X

KW - Obesity

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KW - Rats, Sprague-Dawley

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DO - 10.1677/joe-10-0004

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JF - Journal of Endocrinology

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ER -

Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome

Abstract

Keywords

UN SDGs

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