Sensitivity to the satiating effects of exendin 4 is decreased in obesity-prone Osborne-Mendel rats compared to obesity-resistant S5B/PI rats

被引：24
|
作者：
Primeaux, S. D. [1 ]
Barnes, M. J. [1 ]
Braymer, H. D. [1 ]
Bray, G. A. [1 ]
机构：
[1] Pennington Biomed Res Ctr, Dietary Obes Lab, Baton Rouge, LA 70808 USA
来源：
INTERNATIONAL JOURNAL OF OBESITY | 2010年 / 34卷 / 09期
关键词：
obesity-prone; obesity-resistant; preproglucagon; GLP-1; High-fat diet; exendin; 4; GLUCAGON-LIKE PEPTIDE-1; FAT FOOD-INTAKE; GUT PEPTIDES; GASTROINTESTINAL HORMONES; APPETITE CONTROL; GENE-EXPRESSION; NEUROPEPTIDE-Y; BODY-WEIGHT; MINIREVIEW; SATIETY;
D O I：
10.1038/ijo.2010.78
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Background: Osborne-Mendel (OM) rats are prone to obesity when fed a high-fat diet, whereas S5B/PI (S5B) rats are resistant to diet-induced obesity when fed the same diet. OM rats have a decreased satiation response to fatty acids infused in the gastrointestinal tract, compared to S5B rats. One possible explanation is that OM rats are less sensitive to the satiating hormone, glucagon-like peptide 1 (GLP-1). GLP-1 is produced in the small intestine and is released in response to a meal. The current experiments examined the role of GLP-1 in OM and S5B rats. Methods: Experiment 1 examined preproglucagon mRNA expression in the ileum of OM and S5B rats fed a high-fat (55% kcal) or low-fat (10% kcal) diet. Experiment 2 investigated the effects of a 2 h high-fat meal after a 24 h fast in OM and S5B rats on circulating GLP-1 (active) levels. Experiment 3 examined the effects of exendin-4 (GLP-1 receptor agonist) administration on the intake of a high-fat or a low-fat diet in OM and S5B rats. Results: Preproglucagon mRNA levels were increased in the ileum of OM rats compared to S5B rats and were increased by high-fat diet in OM and S5B rats. OM and S5B rats exhibited a similar meal-initiated increase in circulating GLP-1 (active) levels. Exendin-4 dose dependently decreased food intake to a greater extent in S5B rats compared to OM rats. The intake of low-fat diet, compared to the intake of high-fat diet, was more sensitive to the effects of exendin-4 in these strains. Conclusions: These results suggest that though OM and S5B rats have similar preproglucagon mRNA expression in the ileum and circulating GLP-1 levels, OM rats are less sensitive to the satiating effects of GLP-1. Therefore, dysregulation of the GLP-1 system may be a mechanism through which OM rats overeat and gain weight. International Journal of Obesity (2010) 34, 1427-1433; doi: 10.1038/ijo.2010.78; published online 20 April 2010
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页码：1427 / 1433
页数：7
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