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Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome

Michel Bernier1, Dylan Harney2, Yen Chin Koay2,3

  • 1Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 USA.

NPJ Aging and Mechanisms of Disease
|July 28, 2020
PubMed

Insights

Disulfiram, an alcohol-aversive drug, effectively reduced body weight and improved metabolic health in mice. This repurposed drug shows promise as a novel anti-obesity intervention by activating autophagy and influencing key metabolic pathways.

Area of Science:

  • Metabolic disease research
  • Pharmacology
  • Obesity interventions

Background:

  • Obesity is a growing global health crisis with limited effective treatments.
  • Disulfiram is an alcohol-aversive drug with potential but poorly understood metabolic effects.

Purpose of the Study:

  • To investigate the anti-obesity effects of disulfiram.
  • To elucidate the molecular mechanisms underlying disulfiram's metabolic actions.

Main Methods:

  • Administered disulfiram to mice on an obesogenic diet.
  • Performed integrated transcriptomic and proteomic analysis of liver tissues from mice and rats.
  • Utilized cell culture to assess disulfiram's effect on autophagy.

Main Results:

  • Disulfiram treatment decreased feeding efficiency, body weight, and increased energy expenditure.
  • Improved glucose tolerance and insulin sensitivity were observed.
  • Molecular analysis revealed disulfiram impacts lipid metabolism, energy, redox, and detoxification pathways.
  • Disulfiram robustly activated autophagy in cell culture.

Conclusions:

  • Repurposing disulfiram demonstrates significant potential as an anti-obesity strategy.
  • Disulfiram's metabolic benefits may be mediated through autophagy activation and modulation of key metabolic pathways.
  • Further research into disulfiram's efficacy and safety for obesity treatment is warranted.
Keywords:
Metabolic syndromeObesity

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