Obesity is a top public health concern, and a molecule that safely treats obesity is urgently needed. Disulfiram (known commercially as Antabuse), an FDA-approved treatment for chronic alcohol addiction, exhibits anti-inflammatory properties and helps protect against certain types of cancer. Here, we show that in mice disulfiram treatment prevented body weight gain and abrogated the adverse impact of an obesogenic diet on insulin responsiveness while mitigating liver steatosis and pancreatic islet hypertrophy. Additionally, disulfiram treatment reversed established diet-induced obesity and metabolic dysfunctions in middle-aged mice. Reductions in feeding efficiency and increases in energy expenditure were associated with body weight regulation in response to long-term disulfiram treatment. Loss of fat tissue and an increase in liver fenestrations were also observed in rats on disulfiram. Given the potent anti-obesogenic effects in rodents, repurposing disulfiram in the clinic could represent a new strategy to treat obesity and its metabolic comorbidities.

肥胖是一个首要的公共卫生问题，迫切需要一种安全治疗肥胖的分子。双硫仑（商业上称为 Antabuse）是一种 FDA 批准的慢性酒精成瘾治疗方法，具有抗炎特性，有助于预防某些类型的癌症。在这里，我们表明双硫仑治疗在小鼠中阻止了体重增加并消除了致肥胖饮食对胰岛素反应性的不利影响，同时减轻了肝脏脂肪变性和胰岛肥大。此外，双硫仑治疗逆转了中年小鼠饮食诱导的肥胖和代谢功能障碍。喂养效率的降低和能量消耗的增加与响应长期双硫仑治疗的体重调节有关。在服用双硫仑的大鼠中也观察到脂肪组织的减少和肝脏开窗的增加。鉴于啮齿类动物的有效抗致肥胖作用，在临床中重新利用双硫仑可能代表治疗肥胖及其代谢合并症的新策略。