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

International Journal of Obesity volume 34, pages 1427–1433 (2010)Cite this article

Subjects

Abstract

Background:

Osborne–Mendel (OM) rats are prone to obesity when fed a high-fat diet, whereas S5B/Pl (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.

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Acknowledgements

This research was supported by NIH NIDDK 32089 to GA Bray and by NIDDK1P0DK072476. This work used the Animal Models and Phenotyping Core and the Genomics Core facilities that are supported in part by COBRE (NIH P20-RR021945) and NORC (1P30-DK072476) center grants from the National Institute of Health. We thank Christine Blackmon and Katherine Pyburn for their technical assistance on this project.

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  1. Dietary Obesity Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA

    S D Primeaux, M J Barnes, H D Braymer & G A Bray

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  1. S D Primeaux
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  2. M J Barnes
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  4. G A Bray
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Correspondence to S D Primeaux.

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Primeaux, S., Barnes, M., Braymer, H. et al. Sensitivity to the satiating effects of exendin 4 is decreased in obesity-prone Osborne–Mendel rats compared to obesity-resistant S5B/Pl rats. Int J Obes 34, 1427–1433 (2010). https://doi.org/10.1038/ijo.2010.78

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