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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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Preproglucagon mRNA levels were higher in the ileum of OM than S5B rat following 14d access to a high fat or low fat diet. Access to a high fat diet increased preproglucagon mRNA levels in both OM and S5B rats. Preproglucagon mRNA levels were normalized to 18S and are shown as mean ± SEM. * high fat diet vs. low fat diet; # OM vs. S5B; (p<.05).
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Figure 3: Preproglucagon mRNA levels were higher in the ileum of OM than S5B rat following 14d access to a high fat or low fat diet. Access to a high fat diet increased preproglucagon mRNA levels in both OM and S5B rats. Preproglucagon mRNA levels were normalized to 18S and are shown as mean ± SEM. * high fat diet vs. low fat diet; # OM vs. S5B; (p<.05).

Mentions: Preproglucagon mRNA levels were measured in ileal enterocytes of OM and S5B rats following 2 weeks access to either a high fat or a low fat diet. A between-subjects ANOVA revealed a main effect for strain (F(1,35) = 16.07, p< .0005; See Figure 3). Post-hoc analyses indicated significantly higher levels of preproglucagon mRNA in the ileal enterocytes of OM rats fed a low fat diet compared to S5B rats fed a low fat diet (p<.05). Additionally, the consumption of a high fat diet increased preproglucagon mRNA levels in both OM and S5B rats (p<.05). There was a 20.5% ± 0.15 vs. 93.3% ± 0.25% (mean ± SEM) increase in preproglucagon mRNA levels in high fat fed OM and S5B rats compared to low fat fed OM and S5B rats, respectively (t(17)=2.39, p<.05).


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)

Preproglucagon mRNA levels were higher in the ileum of OM than S5B rat following 14d access to a high fat or low fat diet. Access to a high fat diet increased preproglucagon mRNA levels in both OM and S5B rats. Preproglucagon mRNA levels were normalized to 18S and are shown as mean ± SEM. * high fat diet vs. low fat diet; # OM vs. S5B; (p<.05).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Preproglucagon mRNA levels were higher in the ileum of OM than S5B rat following 14d access to a high fat or low fat diet. Access to a high fat diet increased preproglucagon mRNA levels in both OM and S5B rats. Preproglucagon mRNA levels were normalized to 18S and are shown as mean ± SEM. * high fat diet vs. low fat diet; # OM vs. S5B; (p<.05).
Mentions: Preproglucagon mRNA levels were measured in ileal enterocytes of OM and S5B rats following 2 weeks access to either a high fat or a low fat diet. A between-subjects ANOVA revealed a main effect for strain (F(1,35) = 16.07, p< .0005; See Figure 3). Post-hoc analyses indicated significantly higher levels of preproglucagon mRNA in the ileal enterocytes of OM rats fed a low fat diet compared to S5B rats fed a low fat diet (p<.05). Additionally, the consumption of a high fat diet increased preproglucagon mRNA levels in both OM and S5B rats (p<.05). There was a 20.5% ± 0.15 vs. 93.3% ± 0.25% (mean ± SEM) increase in preproglucagon mRNA levels in high fat fed OM and S5B rats compared to low fat fed OM and S5B rats, respectively (t(17)=2.39, p<.05).

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