Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome
Abstract There is an unmet need and urgency to find safe and effective anti-obesity interventions. Our recent study in mice fed on obesogenic diet found that treatment with the alcohol aversive drug disulfiram reduced feeding efficiency and led to a decrease in body weight and an increase in energy...
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2020
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oai:doaj.org-article:6764f6e5a0bd403f9dbc67a86fdcd3e62021-12-02T17:03:48ZElucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome10.1038/s41514-020-0046-62056-3973https://doaj.org/article/6764f6e5a0bd403f9dbc67a86fdcd3e62020-07-01T00:00:00Zhttps://doi.org/10.1038/s41514-020-0046-6https://doaj.org/toc/2056-3973Abstract There is an unmet need and urgency to find safe and effective anti-obesity interventions. Our recent study in mice fed on obesogenic diet found that treatment with the alcohol aversive drug disulfiram reduced feeding efficiency and led to a decrease in body weight and an increase in energy expenditure. The intervention with disulfiram improved glucose tolerance and insulin sensitivity, and mitigated metabolic dysfunctions in various organs through poorly defined mechanisms. Here, integrated analysis of transcriptomic and proteomic data from mouse and rat livers unveiled comparable signatures in response to disulfiram, revealing pathways associated with lipid and energy metabolism, redox, and detoxification. In cell culture, disulfiram was found to be a potent activator of autophagy, the malfunctioning of which has negative consequences on metabolic regulation. Thus, repurposing disulfiram may represent a potent strategy to combat obesity.Michel BernierDylan HarneyYen Chin KoayAntonio DiazAbhishek SinghDevin WahlTamara PulpitelAhmed AliVince GuiterrezSarah J. MitchellEun-Young KimJohn MachNathan L. PriceMiguel A. AonDavid G. LeCouteurVictoria C. CoggerCarlos Fernandez-HernandoJohn O’SullivanMark LaranceAna Maria CuervoRafael de CaboNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 6, Iss 1, Pp 1-11 (2020) |
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DOAJ |
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DOAJ |
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EN |
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Geriatrics RC952-954.6 |
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Geriatrics RC952-954.6 Michel Bernier Dylan Harney Yen Chin Koay Antonio Diaz Abhishek Singh Devin Wahl Tamara Pulpitel Ahmed Ali Vince Guiterrez Sarah J. Mitchell Eun-Young Kim John Mach Nathan L. Price Miguel A. Aon David G. LeCouteur Victoria C. Cogger Carlos Fernandez-Hernando John O’Sullivan Mark Larance Ana Maria Cuervo Rafael de Cabo Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome |
| description |
Abstract There is an unmet need and urgency to find safe and effective anti-obesity interventions. Our recent study in mice fed on obesogenic diet found that treatment with the alcohol aversive drug disulfiram reduced feeding efficiency and led to a decrease in body weight and an increase in energy expenditure. The intervention with disulfiram improved glucose tolerance and insulin sensitivity, and mitigated metabolic dysfunctions in various organs through poorly defined mechanisms. Here, integrated analysis of transcriptomic and proteomic data from mouse and rat livers unveiled comparable signatures in response to disulfiram, revealing pathways associated with lipid and energy metabolism, redox, and detoxification. In cell culture, disulfiram was found to be a potent activator of autophagy, the malfunctioning of which has negative consequences on metabolic regulation. Thus, repurposing disulfiram may represent a potent strategy to combat obesity. |
| format |
article |
| author |
Michel Bernier Dylan Harney Yen Chin Koay Antonio Diaz Abhishek Singh Devin Wahl Tamara Pulpitel Ahmed Ali Vince Guiterrez Sarah J. Mitchell Eun-Young Kim John Mach Nathan L. Price Miguel A. Aon David G. LeCouteur Victoria C. Cogger Carlos Fernandez-Hernando John O’Sullivan Mark Larance Ana Maria Cuervo Rafael de Cabo |
| author_facet |
Michel Bernier Dylan Harney Yen Chin Koay Antonio Diaz Abhishek Singh Devin Wahl Tamara Pulpitel Ahmed Ali Vince Guiterrez Sarah J. Mitchell Eun-Young Kim John Mach Nathan L. Price Miguel A. Aon David G. LeCouteur Victoria C. Cogger Carlos Fernandez-Hernando John O’Sullivan Mark Larance Ana Maria Cuervo Rafael de Cabo |
| author_sort |
Michel Bernier |
| title |
Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome |
| title_short |
Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome |
| title_full |
Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome |
| title_fullStr |
Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome |
| title_full_unstemmed |
Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome |
| title_sort |
elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome |
| publisher |
Nature Portfolio |
| publishDate |
2020 |
| url |
https://doaj.org/article/6764f6e5a0bd403f9dbc67a86fdcd3e6 |
| work_keys_str_mv |
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