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Disulfiram Treatment Normalizes Body Weight in Obese Mice.


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.

SUBMITTER: Bernier M 

PROVIDER: S-EPMC7957855 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Disulfiram Treatment Normalizes Body Weight in Obese Mice.

Bernier Michel M   Mitchell Sarah J SJ   Wahl Devin D   Diaz Antonio A   Singh Abhishek A   Seo Wonhyo W   Wang Mingy M   Ali Ahmed A   Kaiser Tamzin T   Price Nathan L NL   Aon Miguel A MA   Kim Eun-Young EY   Petr Michael A MA   Cai Huan H   Warren Alessa A   Di Germanio Clara C   Di Francesco Andrea A   Fishbein Ken K   Guiterrez Vince V   Harney Dylan D   Koay Yen Chin YC   Mach John J   Enamorado Ignacio Navas IN   Pulpitel Tamara T   Wang Yushi Y   Zhang Jing J   Zhang Li L   Spencer Richard G RG   Becker Kevin G KG   Egan Josephine M JM   Lakatta Edward G EG   O'Sullivan John J   Larance Mark M   LeCouteur David G DG   Cogger Victoria C VC   Gao Bin B   Fernandez-Hernando Carlos C   Cuervo Ana Maria AM   de Cabo Rafael R  

Cell metabolism 20200514 2


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 isl  ...[more]

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