Dataset Information

Proteomics analysis of rat liver after disulfiram treatment

ABSTRACT: Obesity has become a global health concern. A molecule that safely prevents and/or treats obesity is urgently needed. Here, we show that long-term diet supplementation of disulfiram (DSF, Antabuse®), an FDA-approved drug, abrogated the adverse impact of an obesogenic diet on insulin responsiveness, while mitigating liver steatosis, cardiovascular remodeling, and pancreatic islet hypertrophy in mice. Additionally, DSF treatment of already obese male and female mice reversed weight gain and alleviated metabolic dysfunctions. Loss of fat tissue and increase in liver fenestrations were also observed in rats on DSF. Transcriptomics and proteomics analyses of mouse and rat livers unveiled comparable signatures, as revealed by pathways associated with lipid and energy metabolism, redox, and detoxification. Mechanistically, markers of hepatic oxidative stress were abrogated in DSF-treated mice through activation of ALDH2 and GST activities in vivo and stimulation of autophagic flux in vitro. Thus, repurposing DSF may represent a new strategy to combat obesity and reverse the associated metabolic disorders in human.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Liver

SUBMITTER: Mark Larance

LAB HEAD: Mark Larance

PROVIDER: PXD016793 | Pride | 2020-05-15

REPOSITORIES: Pride

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			Action	DRS
	20190325_QEHFX1_DW_EXP1_Control_644471.raw	Raw
	20190325_QEHFX1_DW_EXP1_Control_644472.raw	Raw
	20190325_QEHFX1_DW_EXP1_Control_644481.raw	Raw
	20190325_QEHFX1_DW_EXP1_Control_644482.raw	Raw
	20190325_QEHFX1_DW_EXP1_Control_644491.raw	Raw

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Publications

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

Bernier Michel M Harney Dylan D Koay Yen Chin YC Diaz Antonio A Singh Abhishek A Wahl Devin D Pulpitel Tamara T Ali Ahmed A Guiterrez Vince V Mitchell Sarah J SJ Kim Eun-Young EY Mach John J Price Nathan L NL Aon Miguel A MA LeCouteur David G DG Cogger Victoria C VC Fernandez-Hernando Carlos C O'Sullivan John J Larance Mark M Cuervo Ana Maria AM de Cabo Rafael R de Cabo Rafael R

NPJ aging and mechanisms of disease 20200721

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 anal ...[more]

PMID: 32714562

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