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Cited by 26Pharmacology and Obesity TreatmentRegulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic Diseases

Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats

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Omran, Ziad, Sheikh, Ryan, Baothman, Othman A, Zamzami, Mazin A, Alarjah, Mohamed·2020·Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
DOI 10.2147/dmso.s254267PMC PMC7210036
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Abstract

BACKGROUND AND OBJECTIVES: A drug repurposing strategy is an approach for identifying new therapeutic uses for approved or investigational drugs. Thanks to the moderate cost of repurposing a drug compared to bringing new chemical entity to the market, drug repurposing is rapidly gaining ground. The aim of this work is to study the anti-obesity effect of disulfiram (DSF), an irreversible aldehyde dehydrogenase inhibitor approved by the Food and Drug Administration (FDA) to treat chronic alcoholism since 1951. METHODS: Thirty male Albino rats were randomly assigned to six groups. G1, the control group, was given a standard diet. G2, the positive control group, was given a high-fat diet (HFD). G3 was given an HFD, and DSF 50 mg/kg/day was administered orally from day one for six weeks. G4 was given an HFD, and DSF 200 mg/kg/day was administered orally from day one for six weeks. G5 was given an HFD for six weeks; then treatment started with 50 mg/kg/day DSF orally. G6 was given an HFD for six weeks; then treatment started with 200 mg/kg/day DSF orally for three weeks. The body weight, food consumption and blood glucose levels were monitored over the given time interval. RESULTS: Both doses of DSF significantly limited the body weight gain caused by an HFD for the treated animals. HF-fed rats received 50 and 200 mg/kg/day of DSF had their body weight increased by 51.93 ± 7.89% and 20.88 ± 15.05% respectively, whereas the body weight of control animals increased by 93.1 ± 20.04%. DSF also significantly decreased the body weight of obese animals. At 50 and 200 mg/kg/day of DSF, HF-fed rats lost 16.74 ± 8.61% and 23.9 ± 3.93% respectively, as their untreated counterparts had their body weight increased by 11.85 ± 3.79% after three weeks of treatment, thus restoring a body weight matching those who received a standard diet. CONCLUSION: FDA-approved disulfiram has a strong anti-obesity effect on HFD-fed rats.

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  • DIS potently inhibits ALDH1A1 more than ALDH2; ALDH1A1 disruption confers diet-induced obesity resistance in rodents and reduces fat mass in mice/dogs without viability defects.

    “It potently inhibits ALDH1A1 (more than ALDH2), which converts retinaldehyde to retinoic acid and is overexpressed in obese individuals; ALDH1A1 disruption confers diet-induced obesity resistance in rodents and reduces fat mass in mice/dogs without viability defects.126”

    From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [126]

    The Introduction says disulfiram inhibits Aldh1a1 more potently than Aldh2 and reports that disrupting Aldh1a1 confers resistance to diet-induced obesity. It reports reduced body weight in mice, but reduced fat mass specifically in dogs; it does not establish reduced fat mass in mice. It also reports no growth or survival defects in Aldh1a1-deficient mice, not dogs. (LLM, conf=0.84)

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Authors
Omran, Z., Sheikh, R., Baothman, O. A., Zamzami, M. A., & Alarjah, M.
Affiliations
  • Umm al-Qura University (SA)
  • King Abdulaziz University (SA)
Corresponding author
Omran, Ziad
ORCID
Venue
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Publisher
Informa UK Limited
Published
2020-05
Volume
Volume 13
Pages
1473-1480
ISSN
1178-7007 (ISSN-L)
DOI
10.2147/dmso.s254267
PMC
PMC7210036
OpenAlex
W3022178033
Cited by
26
References
35
Citations by year
2026: 6 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 4
FWCI
1.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Metabolic Syndrome and Obesity (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Funders
  • King Abdulaziz City for Science and Technology (2-17-03-007-0010)
  • King Abdullah International Medical Research Center
Topics
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
disulfiram, drug repurposing, anti-obesity, high-fat diet, obesity, weight gain, aldehyde dehydrogenase inhibitors, weight loss, blood glucose, dietary intake

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