Disulfiram Treatment Normalizes Body Weight in Obese Mice
Michel Bernier1, Sarah J Mitchell1, Devin Wahl2
1Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
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.
Insights
Disulfiram, an existing drug, effectively combats obesity in mice by reducing weight gain and improving metabolic health. This suggests repurposing disulfiram could be a novel strategy for treating obesity and related conditions.
Area of Science:
- Metabolic research
- Pharmacology
- Public health
Background:
- Obesity is a significant global health issue requiring safe and effective treatments.
- Disulfiram (Antabuse) is an FDA-approved medication for alcohol addiction with known anti-inflammatory and anti-cancer properties.
Purpose of the Study:
- To investigate the potential of disulfiram as a novel therapeutic agent for obesity and its associated metabolic dysfunctions.
Main Methods:
- Disulfiram treatment was administered to mice on an obesogenic diet to assess its effects on body weight, insulin sensitivity, liver steatosis, and pancreatic islet hypertrophy.
- Established diet-induced obesity in middle-aged mice was reversed using disulfiram.
- Physiological changes including feeding efficiency, energy expenditure, fat tissue mass, and liver fenestrations were analyzed in rodents.
Main Results:
- Disulfiram treatment prevented weight gain and improved insulin responsiveness in mice fed an obesogenic diet.
- The drug reversed established obesity and metabolic dysfunction in middle-aged mice.
- Observed effects included reduced feeding efficiency, increased energy expenditure, fat loss, and enhanced liver fenestrations in rodents.
Conclusions:
- Disulfiram demonstrates potent anti-obesogenic effects in preclinical models.
- Repurposing disulfiram presents a promising new clinical strategy for managing obesity and its comorbidities.
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