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Combination of Obesity and High-Fat Feeding Diminishes Sensitivity to GLP-1R Agonist Exendin-4
Obesity and high-fat diet reduce response to the diabetes drug exendin-4
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Abstract
Obese-prone rats exhibit reduced endogenous levels and impaired signaling compared to obese-resistant rats during high-energy/high-fat feeding.
- Exogenous administration of the GLP-1R agonist effectively suppressed food intake in both obese-prone and obese-resistant rats when fed chow.
- During high-energy/high-fat feeding, obese-prone rats showed significantly less suppression of food intake compared to obese-resistant rats across all tested doses of exendin-4.
- Obese-prone rats had downregulated GLP-1 receptor mRNA expression in the vagal nodose ganglia.
- Plasma GLP-1 levels were significantly lower in high-energy/high-fat-fed obese-prone rats compared to obese-resistant rats.
- Obese-prone rats also displayed decreased protein levels of GLP-1 in the intestinal epithelium and a reduced number of L cells in the distal ileum.
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Key numbers
total:< 0.01; active:< 0.001
Decrease in Plasma Levels
Comparison of plasma levels in HE/HF-fed OP vs. OR rats
0.625 and 1.25 μg/kg
Sensitivity to Ex-4
Ex-4 doses tested in OP and OR rats during HE/HF feeding
< 0.0001
L Cells Count Reduction
Comparison of L cell counts in OP vs. OR rats on HE/HF diet