胰高血糖素样肽-1 激动剂 exendin-4 可降低下丘脑肥胖大鼠的体重和热量摄入。
Glucagon-like peptide-1 agonist exendin-4 leads to reduction of weight and caloric intake in a rat model of hypothalamic obesity.
机构信息
Seattle Children's Research Institute, Seattle, Wash. 98101, USA.
出版信息
Horm Res Paediatr. 2012;78(1):47-53. doi: 10.1159/000338464. Epub 2012 Jul 20.
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.
背景
内侧下丘脑核损伤引起的下丘脑性肥胖是一个治疗难题。胰高血糖素样肽-1 激动剂 exenatide（exendin-4 的合成版本），用于治疗糖尿病，通过后脑信号导致体重减轻。
方法
我们在已建立的内侧下丘脑损伤大鼠模型中测试了 Ex4。损伤和对照动物每天接受 1µg·kg(-1) Ex4 或生理盐水的腹腔内注射，共 9 天。
结果
在我们的大鼠模型中，与生理盐水相比，Ex4 治疗期间观察到基线食物摄入量的百分比差异（损伤-20.8%，对照-13.6%；p<0.001）和体重变化的百分比差异（损伤-4.9%/9 天，对照-3.2%/9 天；p<0.05）。
结论
Ex4 导致食物摄入量和体重减少。需要进一步的研究来阐明其对能量平衡的影响，并将 Ex4 确立为治疗下丘脑性肥胖的潜在药物。
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