Disulfiram Treatment Normalizes Body Weight in Obese Mice.

Animals Anti-Obesity Agents / pharmacology Body Weight / drug effects Diet / adverse effects Disulfiram / pharmacology Female Male Mice Mice, Inbred C57BL Mice, Knockout Obesity / chemically induced Rats Rats, Sprague-Dawley
beta-cell hyperplasia fibrosis hepatic steatosis inflammation insulin resistance obesity weight gain

Journal

Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170

Informations de publication

Date de publication:
04 08 2020
Historique:
received: 16 03 2020
revised: 02 04 2020
accepted: 24 04 2020
pubmed: 16 5 2020
medline: 10 11 2021
entrez: 16 5 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.cmet.2020.04.019 PMID: 32413333 PMC: PMC7957855
pubmed: 32413333
pii: S1550-4131(20)30236-9
doi: 10.1016/j.cmet.2020.04.019
pmc: PMC7957855
mid: NIHMS1591438
pii:
doi:

Substances chimiques

Anti-Obesity Agents 0
Disulfiram TR3MLJ1UAI

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

203-214.e4

Subventions

Organisme : NHLBI NIH HHS
ID : R35 HL135820
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG021904
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 AG999999
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG021904
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020541
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG054108
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG038072
Pays : United States
Organisme : NIDDK NIH HHS
ID : P60 DK020541
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK098408
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG031782
Pays : United States

Informations de copyright

Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

Michel Bernier (M)

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: bernierm@mail.nih.gov.

Sarah J Mitchell (SJ)

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

Devin Wahl (D)

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA; Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Ageing and Alzheimer's Institute, ANZAC Research Institute, Concord Clinical School/Sydney Medical School, Concord, NSW 2139, Australia.

Antonio Diaz (A)

Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, New York, NY 10461, USA.

Abhishek Singh (A)

Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.

Wonhyo Seo (W)

Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.

Mingy Wang (M)

Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Ahmed Ali (A)

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

Tamzin Kaiser (T)

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

Nathan L Price (NL)

Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.

Miguel A Aon (MA)

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA; Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Eun-Young Kim (EY)

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA; Functional Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea.

Michael A Petr (MA)

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

Huan Cai (H)

Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Alessa Warren (A)

Ageing and Alzheimer's Institute, ANZAC Research Institute, Concord Clinical School/Sydney Medical School, Concord, NSW 2139, Australia.

Clara Di Germanio (C)

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

Andrea Di Francesco (A)

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

Ken Fishbein (K)

Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Vince Guiterrez (V)

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

Dylan Harney (D)

Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.

Yen Chin Koay (YC)

Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Heart Research Institute, The University of Sydney, Sydney, NSW 2042, Australia.

John Mach (J)

Kolling Institute of Medical Research and Sydney Medical School, University of Sydney, Sydney, NSW 2065, Australia.

Ignacio Navas Enamorado (IN)

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

Tamara Pulpitel (T)

Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Ageing and Alzheimer's Institute, ANZAC Research Institute, Concord Clinical School/Sydney Medical School, Concord, NSW 2139, Australia.

Yushi Wang (Y)

Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Jing Zhang (J)

Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Li Zhang (L)

Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Richard G Spencer (RG)

Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Kevin G Becker (KG)

Laboratory of Genetics, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Josephine M Egan (JM)

Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Edward G Lakatta (EG)

Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

John O'Sullivan (J)

Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Heart Research Institute, The University of Sydney, Sydney, NSW 2042, Australia.

Mark Larance (M)

Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.

David G LeCouteur (DG)

Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Ageing and Alzheimer's Institute, ANZAC Research Institute, Concord Clinical School/Sydney Medical School, Concord, NSW 2139, Australia.

Victoria C Cogger (VC)

Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Ageing and Alzheimer's Institute, ANZAC Research Institute, Concord Clinical School/Sydney Medical School, Concord, NSW 2139, Australia.

Bin Gao (B)

Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.

Carlos Fernandez-Hernando (C)

Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.

Ana Maria Cuervo (AM)

Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, New York, NY 10461, USA.

Rafael de Cabo (R)

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: decaboRa@mail.nih.gov.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Disulfiram Treatment Normalizes Body Weight in...
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