Disulfiram Treatment Normalizes Body Weight in Obese Mice

• Published in: Cell metabolism 2020-08, Vol.32 (2), p.203-214.e4
• Main Authors: Bernier, Michel, Mitchell, Sarah J., Wahl, Devin, Diaz, Antonio, Singh, Abhishek, Seo, Wonhyo, Wang, Mingy, Ali, Ahmed, Kaiser, Tamzin, Price, Nathan L., Aon, Miguel A., Kim, Eun-Young, Petr, Michael A., Cai, Huan, Warren, Alessa, Di Germanio, Clara, Di Francesco, Andrea, Fishbein, Ken, Guiterrez, Vince, Harney, Dylan, Koay, Yen Chin, Mach, John, Enamorado, Ignacio Navas, Pulpitel, Tamara, Wang, Yushi, Zhang, Jing, Zhang, Li, Spencer, Richard G., Becker, Kevin G., Egan, Josephine M., Lakatta, Edward G., O’Sullivan, John, Larance, Mark, LeCouteur, David G., Cogger, Victoria C., Gao, Bin, Fernandez-Hernando, Carlos, Cuervo, Ana Maria, de Cabo, Rafael
• Format: Article
• Language: English
• Subjects: beta-cell hyperplasia; fibrosis; hepatic steatosis; inflammation; insulin resistance; obesity; weight gain
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2020.04.019

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. [Display omitted] •Prophylactic and therapeutic effects of disulfiram (DSF) on diet-induced obesity•DSF reduces feeding efficiency and restores insulin responsiveness•DSF alleviates hepatosteatosis and pancreatic islet hyperplasia in obese mice•The metabolic benefits of DSF are preserved in Aldh2 KO mice fed an obesogenic diet In this study, Bernier et al. report on the off-label use of disulfiram to combat diet-induced obesity in mice through normalization of body weight and improvement of various physiological outcomes related to body composition and insulin responsiveness.