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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.

Primeaux SD, Barnes MJ, Braymer HD, Bray GA - Int J Obes (Lond) (2010)

Bottom Line: GLP-1 is produced in the small intestine and is released in response to a meal.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.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.

View Article: PubMed Central - PubMed

Affiliation: Dietary Obesity Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. Stefany.Primeaux@pbrc.edu

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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A. S5B rats were administered varying doses of Ex-4 following a 24h fast and given access to either low fat or high fat diet. Ex-4 dose dependently decreased high fat and low fat diet intake at 1h, 2h, and 4h. B. Following a 24h fast, OM were administered Ex-4 and low fat and high fat intake were measured. The two highest doses of Ex-4 (5μg/kg and 10μg/kg) decreased low fat diet intake at 1h, 2h, and 4h and high fat diet intake at 1h. The highest dose of Ex-4 decreased high fat food intake at 2h, but not at 4h. Data are expressed as cumulative food intake in kilocalories (kcal) and shown as mean ± SEM. * saline vs. Ex-4, (p<.05).
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Figure 5: A. S5B rats were administered varying doses of Ex-4 following a 24h fast and given access to either low fat or high fat diet. Ex-4 dose dependently decreased high fat and low fat diet intake at 1h, 2h, and 4h. B. Following a 24h fast, OM were administered Ex-4 and low fat and high fat intake were measured. The two highest doses of Ex-4 (5μg/kg and 10μg/kg) decreased low fat diet intake at 1h, 2h, and 4h and high fat diet intake at 1h. The highest dose of Ex-4 decreased high fat food intake at 2h, but not at 4h. Data are expressed as cumulative food intake in kilocalories (kcal) and shown as mean ± SEM. * saline vs. Ex-4, (p<.05).

Mentions: Food intake was measured following Ex-4 administration in OM and S5B rats fed either a high fat or a low fat diet. Several significant interaction effects were detected between time following injection, dose of Ex-4 and rat strain (time × Ex-4 × strain, F(9,147) = 4.38, p<.0001; time × Ex-4, F(9,147) = 3.94, p< .0001; time × strain F(3,147) = 3.27, p<.02; Ex-4 × strain F(3,49) = 11.18, p<.00001). Post-hoc tests revealed that 1h, 2h and 4h following injection, obesity-resistant S5B rats receiving 1μg/kg, 5μg/kg and 10μg/kg Ex-4 ate significantly less high fat and low fat diet than saline-treated control S5B rats (p<.05; See Figure 5A). Additionally, post-hoc analyses revealed decreases in low fat food intake in obesity-prone OM rats at 5μg/kg and 10μg/kg of Ex-4 (p<.05; See Figure 5B) compared to saline-treated control OM rats at 1h, 2h and 4h. High fat food intake was decreased in OM rats receiving 5μg/kg and 10μg/kg Ex-4 at 1h following administration and in OM rats receiving 10μg/kg Ex-4 at 2h following administration (p<.05; See Figure 5B).


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

Primeaux SD, Barnes MJ, Braymer HD, Bray GA - Int J Obes (Lond) (2010)

A. S5B rats were administered varying doses of Ex-4 following a 24h fast and given access to either low fat or high fat diet. Ex-4 dose dependently decreased high fat and low fat diet intake at 1h, 2h, and 4h. B. Following a 24h fast, OM were administered Ex-4 and low fat and high fat intake were measured. The two highest doses of Ex-4 (5μg/kg and 10μg/kg) decreased low fat diet intake at 1h, 2h, and 4h and high fat diet intake at 1h. The highest dose of Ex-4 decreased high fat food intake at 2h, but not at 4h. Data are expressed as cumulative food intake in kilocalories (kcal) and shown as mean ± SEM. * saline vs. Ex-4, (p<.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2910155&req=5

Figure 5: A. S5B rats were administered varying doses of Ex-4 following a 24h fast and given access to either low fat or high fat diet. Ex-4 dose dependently decreased high fat and low fat diet intake at 1h, 2h, and 4h. B. Following a 24h fast, OM were administered Ex-4 and low fat and high fat intake were measured. The two highest doses of Ex-4 (5μg/kg and 10μg/kg) decreased low fat diet intake at 1h, 2h, and 4h and high fat diet intake at 1h. The highest dose of Ex-4 decreased high fat food intake at 2h, but not at 4h. Data are expressed as cumulative food intake in kilocalories (kcal) and shown as mean ± SEM. * saline vs. Ex-4, (p<.05).
Mentions: Food intake was measured following Ex-4 administration in OM and S5B rats fed either a high fat or a low fat diet. Several significant interaction effects were detected between time following injection, dose of Ex-4 and rat strain (time × Ex-4 × strain, F(9,147) = 4.38, p<.0001; time × Ex-4, F(9,147) = 3.94, p< .0001; time × strain F(3,147) = 3.27, p<.02; Ex-4 × strain F(3,49) = 11.18, p<.00001). Post-hoc tests revealed that 1h, 2h and 4h following injection, obesity-resistant S5B rats receiving 1μg/kg, 5μg/kg and 10μg/kg Ex-4 ate significantly less high fat and low fat diet than saline-treated control S5B rats (p<.05; See Figure 5A). Additionally, post-hoc analyses revealed decreases in low fat food intake in obesity-prone OM rats at 5μg/kg and 10μg/kg of Ex-4 (p<.05; See Figure 5B) compared to saline-treated control OM rats at 1h, 2h and 4h. High fat food intake was decreased in OM rats receiving 5μg/kg and 10μg/kg Ex-4 at 1h following administration and in OM rats receiving 10μg/kg Ex-4 at 2h following administration (p<.05; See Figure 5B).

Bottom Line: GLP-1 is produced in the small intestine and is released in response to a meal.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.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.

View Article: PubMed Central - PubMed

Affiliation: Dietary Obesity Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. Stefany.Primeaux@pbrc.edu

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.

Show MeSH
Related in: MedlinePlus