Elucidating the mechanisms by which disulfiram protects against obesity and metabolic syndrome
| Autor: | Sarah J. Mitchell, Abhishek Singh, John F. O'Sullivan, Victoria C. Cogger, Dylan J. Harney, Nathan L. Price, Eun Young Kim, Yen Chin Koay, Devin Wahl, David G. LeCouteur, Miguel A. Aon, Mark Larance, Tamara Pulpitel, Vince Guiterrez, Ahmed Ali, Antonio Diaz, Ana Maria Cuervo, Rafael de Cabo, Carlos Fernández-Hernando, Michel Bernier, John Mach |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug Aging media_common.quotation_subject Pharmacology Article Transcriptome 03 medical and health sciences 0302 clinical medicine Detoxification Medicine Obesity media_common Activator (genetics) business.industry Autophagy RC952-954.6 medicine.disease Metabolic syndrome 030104 developmental biology Geriatrics Disulfiram Geriatrics and Gerontology business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | npj Aging and Mechanisms of Disease, Vol 6, Iss 1, Pp 1-11 (2020) NPJ Aging and Mechanisms of Disease |
| ISSN: | 2056-3973 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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