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. 2012;78(1):47-53.
doi: 10.1159/000338464. Epub 2012 Jul 20.

Glucagon-like peptide-1 Agonist exendin-4 Leads to Reduction of Weight and Caloric Intake in a Rat Model of Hypothalamic Obesity

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Glucagon-like peptide-1 Agonist exendin-4 Leads to Reduction of Weight and Caloric Intake in a Rat Model of Hypothalamic Obesity

Clinton T Elfers et al. Horm Res Paediatr. .

Abstract

Background: Hypothalamic obesity caused by damage of medial hypothalamic nuclei presents a therapeutic challenge. Glucagon-like peptide-1 agonist exenatide (synthetic version of exendin-4 (Ex4)), used for treatment of diabetes, causes weight loss via hindbrain signaling.

Methods: We tested Ex4 in an established rat model of medial hypothalamic lesions. Lesion and control animals were administered either daily intraperitoneal injections of 1 µg·kg(-1) Ex4 or saline for 9 days.

Results: In our rat model, a significant difference in percent baseline food intake (lesion -20.8%, control -13.6%; p < 0.001) and percent change in body weight (lesion -4.9%/9 days, control -3.2%/9 days; p < 0.05) was observed during Ex4 treatment compared with saline.

Conclusion: Ex4 resulted in reduction of food intake and body weight. Follow-up studies are required to further elucidate its effects on energy homeostasis and to establish Ex4 as a potential drug for treatment of hypothalamic obesity.

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