Department of Surgery, Vanderbilt University Medical Center, Nashville, TN.
Department of Physiology, Midwestern University, Downers Grove, IL.
Diabetes. 2022 Jul 1;71(7):1424-1438. doi: 10.2337/db21-0708.
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.
肉毒杆菌神经毒素（商品名为 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）小鼠的近端肠壁中可导致体重减轻和食物摄入量减少。这与改善高血糖、高血脂以及葡萄糖耐量显著改善有关，而能量消耗没有改变。我们还观察到胃肠道转运加速以及葡萄糖和脂质吸收显著减少，这至少部分解释了观察到的体重减轻和强大的代谢益处，尽管可能由于中枢和/或外周信号发生的全身效应不容忽视。如配对喂养实验所示，观察到的代谢益处在很大程度上与体重减轻无关。这种效果持续了约 8 周，与先前在啮齿动物研究中报告的肉毒杆菌半衰期一样长。这些结果具有重要的临床意义。如果观察到的效果在人类中可转化，那么这种方法可以为治疗方法奠定基础，这些方法旨在实现强大和持续的体重减轻，模仿减重手术的一些益处，而没有其成本和并发症。
