There is an unmet need and urgency to find safe and effective anti-obesity interventions. Our recent study in mice fed on obesogenic diet found that treatment with the alcohol aversive drug disulfiram reduced feeding efficiency and led to a decrease in body weight and an increase in energy expenditure. The intervention with disulfiram improved glucose tolerance and insulin sensitivity, and mitigated metabolic dysfunctions in various organs through poorly defined mechanisms. Here, integrated analysis of transcriptomic and proteomic data from mouse and rat livers unveiled comparable signatures in response to disulfiram, revealing pathways associated with lipid and energy metabolism, redox, and detoxification. In cell culture, disulfiram was found to be a potent activator of autophagy, the malfunctioning of which has negative consequences on metabolic regulation. Thus, repurposing disulfiram may represent a potent strategy to combat obesity.

寻找安全有效的抗肥胖症干预措施尚未得到满足和紧迫性。我们最近在以致肥胖饮食喂养的小鼠中进行的研究发现，用厌恶酒精的药物双硫仑治疗会降低喂养效率，并导致体重减轻和能量消耗增加。双硫仑的干预改善了葡萄糖耐量和胰岛素敏感性，并通过定义不清的机制减轻了各个器官的代谢功能障碍。在这里，对来自小鼠和大鼠肝脏的转录组和蛋白质组学数据的综合分析揭示了对双硫仑的可比特征，揭示了与脂质和能量代谢，氧化还原和排毒相关的途径。在细胞培养中，发现双硫仑是自噬的有效激活剂，其功能失调会对代谢调节产生负面影响。因此，改变二硫仑的用途可能代表对抗肥胖的有效策略。