Disulfiram Treatment Normalizes Body Weight in Obese Mice
Michel Bernier, Sarah J Mitchell, Devin Wahl, Antonio Diaz, Abhishek Singh, Wonhyo Seo, Mingy Wang, Ahmed Ali, Tamzin Kaiser, Nathan L Price, Miguel A Aon, Eun-Young Kim, Michael A Petr, Huan Cai, Alessa Warren, Clara Di Germanio, Andrea Di Francesco, Ken Fishbein, Vince Guiterrez, Dylan Harney, Yen Chin Koay, John Mach, Ignacio Navas Enamorado, Tamara Pulpitel, Yushi Wang, Jing Zhang, Li Zhang, Richard G Spencer, Kevin G Becker, Josephine M Egan, Edward G Lakatta, John O'Sullivan, Mark Larance, David G LeCouteur, Victoria C Cogger, Bin Gao, Carlos Fernandez-Hernando, Ana Maria Cuervo, Rafael de Cabo, Michel Bernier, Sarah J Mitchell, Devin Wahl, Antonio Diaz, Abhishek Singh, Wonhyo Seo, Mingy Wang, Ahmed Ali, Tamzin Kaiser, Nathan L Price, Miguel A Aon, Eun-Young Kim, Michael A Petr, Huan Cai, Alessa Warren, Clara Di Germanio, Andrea Di Francesco, Ken Fishbein, Vince Guiterrez, Dylan Harney, Yen Chin Koay, John Mach, Ignacio Navas Enamorado, Tamara Pulpitel, Yushi Wang, Jing Zhang, Li Zhang, Richard G Spencer, Kevin G Becker, Josephine M Egan, Edward G Lakatta, John O'Sullivan, Mark Larance, David G LeCouteur, Victoria C Cogger, Bin Gao, Carlos Fernandez-Hernando, Ana Maria Cuervo, Rafael de Cabo
Abstract
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.
Keywords: beta-cell hyperplasia; fibrosis; hepatic steatosis; inflammation; insulin resistance; obesity; weight gain.
Conflict of interest statement
Declaration of Interests The authors declare no competing interests.
Published by Elsevier Inc.
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Source: PubMed