Botulinum neurotoxin (available commercially as BOTOX) has been used successfully for treatment of several neuromuscular disorders, including blepharospasm, dystonia, spasticity, and cerebral palsy in children. Our data demonstrate that injection of Botox into the proximal intestinal wall of diet-induced obese (DIO) mice induces weight loss and reduces food intake. This was associated with amelioration of hyperglycemia, hyperlipidemia, and significant improvement of glucose tolerance without alteration of energy expenditure. We also observed accelerated gastrointestinal transit and significant reductions in glucose and lipid absorption, which may account, at least in part, for the observed weight loss and robust metabolic benefits, although possible systemic effects occurring as a consequence of central and/or peripheral signaling cannot be ignored. The observed metabolic benefits were found to be largely independent of weight loss, as demonstrated by pair-feeding experiments. Effects lasted ∼8 weeks, for as long as the half-life of Botox as reported in prior rodent studies. These results have valuable clinical implications. If the observed effects are translatable in humans, this approach could lay the foundation for therapeutic approaches geared toward robust and sustained weight loss, mimicking some of the benefits of bariatric operations without its cost and complications.

中文翻译：

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将肉毒杆菌注射到饮食引起的肥胖小鼠的近端肠壁可导致体重减轻并改善葡萄糖和脂肪耐受性。

肉毒杆菌神经毒素（商业上可称为 BOTOX）已成功用于治疗多种神经肌肉疾病，包括眼睑痉挛、肌张力障碍、痉挛和儿童脑瘫。我们的数据表明，将肉毒杆菌注射到饮食诱导肥胖（DIO）小鼠的近端肠壁可导致体重减轻并减少食物摄入量。这与高血糖、高脂血症的改善以及糖耐量的显着改善而不改变能量消耗有关。我们还观察到胃肠道运输加速以及葡萄糖和脂质吸收显着减少，这可能至少部分解释了观察到的体重减轻和强大的代谢益处，尽管中枢和/或外周信号传导可能产生的全身效应不容忽视。正如配对喂养实验所证明的那样，观察到的代谢益处在很大程度上与体重减轻无关。效果持续约 8 周，与之前啮齿动物研究中报告的 Botox 半衰期一样长。这些结果具有有价值的临床意义。如果观察到的效果可以转化为人类，那么这种方法可以为稳健和持续减肥的治疗方法奠定基础，模仿减肥手术的一些好处，而无需成本和并发症。与先前啮齿动物研究中报道的肉毒杆菌毒素的半衰期一样长。这些结果具有有价值的临床意义。如果观察到的效果可以转化为人类，那么这种方法可以为稳健和持续减肥的治疗方法奠定基础，模仿减肥手术的一些好处，而无需成本和并发症。与先前啮齿动物研究中报道的肉毒杆菌毒素的半衰期一样长。这些结果具有有价值的临床意义。如果观察到的效果可以转化为人类，那么这种方法可以为稳健和持续减肥的治疗方法奠定基础，模仿减肥手术的一些好处，而无需成本和并发症。