Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long-term disulfiram supplementation activates an anti-inflammatory metabolic network to lower diet-induced obesity and related co-morbidities

ABSTRACT: According to the WHO, the obesity epidemic has become a global and grave public health concern. A small molecule to safely prevent and/or treat the negative pathophysiological consequences of obesity is urgently needed. We conducted long-term supplementation of the FDA-approved anti-inflammatory drug disulfiram (DSF, Antabuse®) in mice fed standard and high-fat diet (HFD), and measured various indicators of health in the animals. Our results uncover an abrogation of the adverse impact of HFD on insulin responsiveness and metabolic fitness through improvements in pancreatic islet morphology and b-cell function along with reduced occurrence of liver injury and cardiovascular remodeling, plausibly by its autophagy activating effect. Additionally, the treatment of obese mice with DSF robustly reversed diet-induced metabolic dysfunctions. These results show that the repurposing of DSF may represent a new strategy to combat obesity and associated metabolic disorders in human.

ORGANISM(S): Mus musculus

PROVIDER: GSE110200 | GEO | 2019/02/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Proteomics analysis of rat liver after disulfiram treatment

Project description: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.

2020-05-15 | PXD016793 | Pride

Expression data from Disulfiram or 5-FU treated tumor-initiating hepatocellular carcinoma (HCC) cells.

Project description:Cancer stem cells (CSCs) or tumor-initiating cells (TICs) organize a cellular hierarchy in a similar fashion to normal stem cell systems and exhibit high tumorigenic activity in xenograft transplantation assay. Disulfiram (DSF) could preferentially eradicate TICs, but the molecular machinery of its effect against TICs still remains largely unknown. We found that flow cytometric analyses showed that DSF but not 5-FU drastically reduces the number of tumor-initiating HCC cells. We conducted microarray analyses to examine gene expression profiling in DSF-treated tumor-initiating HCC cells. Purified EpCAM-positive HCC cells treated with Disulfiram or 5-FU were subjected to RNA extraction and hybridization on Agilent microarrays. Data were obtained for tripricate samples from three independent experiments.

2012-11-16 | E-GEOD-42318 | biostudies-arrayexpress

Expression data from Disulfiram or 5-FU treated EpCAM-negative non-tumor-initiating hepatocellular carcinoma (HCC) cells.

Project description:Cancer stem cells (CSCs) or tumor-initiating cells (TICs) organize a cellular hierarchy in a similar fashion to normal stem cell systems and exhibit high tumorigenic activity in xenograft transplantation assay. Disulfiram (DSF) could preferentially eradicate TICs, but the molecular machinery of its effect against TICs still remains largely unknown. We found that DSF but not 5-FU erradicates tumor-initiating HCC cells. To compare the gene expression profiles in EpCAM-positive cells and EpCAM-negative cells, we conducted microarray analyses of EpCAM-negative HCC cells treated with DSF or 5-FU. Purified EpCAM-negative HCC cells treated with Disulfiram or 5-FU were subjected to RNA extraction and hybridization on Agilent microarrays.

2013-03-16 | E-GEOD-45224 | biostudies-arrayexpress

Quantitative proteomics analysis reveals novel insights into mechanisms of action of Disulfiram (DSF)

Project description:The new uses of the old drugs may reduce cost and shortens the production cycle of research and development, especially that approved by FDA for important clinical conditions. Alcohol abuse Disulfiram (DSF) has been proven safe and shows the promising anti-tumor effect in may preclinical studies. However, the potential side effects of DSF on tumor remain unknown. In this study, we explored the role of DSF in cancer cells and searched for the differential expressed protein after DSF treatment in the HeLa cells. To fully understand the mechanism of action of DSF with a systems perspective, we employed a quantitative proteomics strategy to systematically identify potential targets of DSF. In total, 201 proteins were dys-regulated significantly after DSF exposure, implying that they may be potential targets of DSF. Analysis of this data on a system level revealed major changes of proteins involved in diverse biological processes, including metabolic process and response to stimulus.

2021-11-27 | PXD024910 | Pride

Expression data from Disulfiram or 5-FU treated tumor-initiating hepatocellular carcinoma (HCC) cells.

2012-11-16 | GSE42318 | GEO

Disulfiram/Copper induces immunogenic cell death via NPL4 in hepatocellular carcinoma

Project description:Some chemotherapeutic agents have been found to enhance the antitumor immunity by inducing immunogenic cell death (ICD). The combination of disulfiram (DSF) and copper (Cu) has demonstrated anti-tumor effects in a range of malignancies including hepatocellular carcinoma (HCC). However, the potential of DSF/Cu as an ICD inducer and whether it could enhance the efficacy of immune checkpoint blockade in HCC remains unknown. Here, we showed that DSF/Cu-treated HCC cells exhibited characteristics of ICD in vitro, such as calreticulin (CRT) exposure, ATP secretion, high mobility group box 1 (HMGB1) release. DSF/Cu treated HCC cells elicited significant immune memory in a vaccination assay. DSF/Cu treatment promoted dendritic cell activation and maturation. The combination of DSF/Cu and CD47 blockade further facilitated DC maturation and subsequently enhanced CD8+ T cell cytotoxicity. Mechanically, DSF/Cu promoted the nuclear accumulation and aggregation of nuclear protein localization protein 4 (NPL4) to inhibit the ubiquitin-proteasome system, thus induced endoplasmic reticulum (ER) stress. Inhibition of NPL4 induced ICD-associated damage-associated molecular patterns. Collectively, our findings demonstrated that DSF/Cu induced ICD-mediated immune activation in HCC and enhanced the efficacy of CD47 blockade.

2022-10-19 | GSE211734 | GEO

Expression data from Disulfiram or 5-FU treated EpCAM-negative non-tumor-initiating hepatocellular carcinoma (HCC) cells.

Project description:Cancer stem cells (CSCs) or tumor-initiating cells (TICs) organize a cellular hierarchy in a similar fashion to normal stem cell systems and exhibit high tumorigenic activity in xenograft transplantation assay. Disulfiram (DSF) could preferentially eradicate TICs, but the molecular machinery of its effect against TICs still remains largely unknown. We found that DSF but not 5-FU erradicates tumor-initiating HCC cells. To compare the gene expression profiles in EpCAM-positive cells and EpCAM-negative cells, we conducted microarray analyses of EpCAM-negative HCC cells treated with DSF or 5-FU.

2013-03-16 | GSE45224 | GEO

Disulfiram treatment suppresses antibody-producing reactions by inhibiting macrophage activation and B cell pyrimidine metabolism

Project description:Antibody responses, involving B cells, CD4+ T cells, and macrophages, are implicated in autoimmune diseases and organ transplant rejection. We have previously shown that inhibiting FROUNT with disulfiram (DSF) suppresses macrophage activation and migration, effectively treating inflammatory diseases. In this study, we investigated the effectiveness of DSF in antibody-producing reactions. Using a heart transplantation mouse model with antibody-mediated rejection, we administered anti-CD8 antibody to exclude cellular rejection. DSF directly inhibited B cell responses in vitro and significantly reduced plasma donor-specific antibodies and graft antibody deposition in vivo, resulting in prolonged survival of the heart graft. DSF also mediated various effects, including decreased macrophage infiltration and increased Foxp3+ regulatory T-cells in the grafts. Additionally, DSF inhibited pyrimidine metabolism-related gene expression induced by B-cell stimulation. These findings demonstrate that DSF modulates antibody production in the immune response complexity by regulating B-cell and macrophage responses.

2024-04-15 | GSE261712 | GEO

Antifungal activity of the repurposed drug disulfiram against Cryptococcus neoformans.

Project description:Fungal infections have become a clinical challenge due to the emergence of drug-resistance of invasive fungi and a rapid increase of novel pathogens. The development of drug resistance has further restricted the use of antifungal agents. Therefore, there is anurgentneedto searchforalternativetreatmentoptions for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a high human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. In contrast, the effect of DSF on Cryptococcus has yet to be thoroughly researched. This study investigated the antifungal effect and mechanism of DSF againstC. neoformansto provide a new theoretical foundation for treating Cryptococcal infections. In vitro studies demonstrated that DSF inhibitedCryptococcusat minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 μg/mL. Combined antifungal effects were also observed with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. In vivo, DSF exerted asignificantprotectiveeffectforGalleria mellonella infected with C. neoformans.Mechanistic investigations showed that DSF dose-dependently inhibited the melanin, urease, acetaldehyde dehydrogenase, capsule, and biofilm formation or viability ofC. neoformans.Further study indicated DSF affectedC. neoformansby interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways included acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter) AFR2, and iron-sulfur cluster transporter ATM1. These findings contribute to the understanding of mechanisms inC. neoformans, and provide new insights for the application of DSF.

2023-12-31 | GSE248987 | GEO

Effect of perinatal obesity on premature kidney aging signaling

Project description:Chronic Kidney Disease (CKD), a global health burden, is strongly associated with age-related renal function decline, hypertension and diabetes, frequent consequences of obesity. Despite extensive studies the mechanisms determining susceptibility to CKD remain elusive. Clinical evidence together with prior studies from our group showed that perinatal metabolic disorders after maternal obesity adversely affect kidney structure and function throughout life. Since obesity and aging processes converge in similar pathways we tested if perinatal obesity induced by High-Fat Diet (HFD)-fed female mice sensitizes aging-associated mechanism in kidneys of newborn mice. Tissue from the kidney cortex and the kidney medulla was collected from offspring of control or HFD-fed mice.

2022-12-31 | E-MTAB-10954 | biostudies-arrayexpress