Related Experiment Video
Updated: Feb 24, 2026
10:59
Label-Free Imaging of Lipid Storage Dynamics in Caenorhabditis elegans using Stimulated Raman Scattering Microscopy
Published on: May 28, 2021
4.8K
Disulfiram Protects Against Diet-Induced Obesity by Reprogramming Systemic Lipid Partitioning Independent of GSDMD
Babunageswararao Kanuri1, Rohan R Varshney2, Krishna P Maremanda1
1Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
Biorxiv : the Preprint Server for Biology
|February 23, 2026
Summary
Disulfiram (DSF) does not treat obesity by inhibiting gasdermin D (GSDMD). Instead, DSF combats obesity and insulin resistance by reprogramming how the body handles lipids, independent of GSDMD.
Area of Science:
- Metabolic disease
- Pharmacology
- Obesity research
Background:
- Obesity is a significant global health issue with few effective long-term drug treatments.
- Disulfiram (DSF), an FDA-approved medication, has been investigated for metabolic benefits, potentially via gasdermin D (GSDMD) inflammasome inhibition.
Purpose of the Study:
- To investigate the role of GSDMD in diet-induced obesity and insulin resistance.
- To elucidate the mechanism by which DSF exerts its anti-obesity effects.
Main Methods:
- Utilized genetic deletion and antisense-mediated inhibition of GSDMD in mouse models.
- Assessed metabolic parameters, including obesity and insulin resistance, in response to high-fat diet.
- Analyzed systemic lipid handling, lipid oxidation, and fecal fatty acid excretion under various conditions.
Main Results:
- GSDMD is not essential for high-fat diet-induced obesity or insulin resistance.
- DSF effectively prevents obesity and insulin resistance through a GSDMD-independent pathway.
- DSF alters lipid metabolism by suppressing basal lipid oxidation and increasing fecal fatty acid excretion, while enhancing lipid utilization during acute lipid challenge.
Conclusions:
- The findings challenge the existing model linking DSF's metabolic benefits to GSDMD inhibition.
- DSF's anti-obesity effects are primarily mediated by a context-dependent regulation of lipid partitioning, not inflammasome suppression.
More Related Videos
Related Concept Videos
01:20Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion
228
Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...
228
01:25Pharmacokinetics in Obese Patients: Drug Absorption and Distribution
313
Obesity significantly alters the pharmacokinetic processes of drug absorption and distribution, presenting unique challenges in medical treatment. The increased fat tissue and decreased lean muscle in obese individuals can significantly affect how drugs are absorbed into the body and distributed across different tissues. This alteration can lead to variances in the effectiveness and safety of medications, necessitating adjustments in dosing or drug selection for obese patients.One notable...
313
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
721
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
721
01:19Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
650
α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
Acarbose and miglitol are...
650
01:21Drug Dosing: Obese Patients
303
In the United States, obesity is a prominent concern. It is linked to heightened mortality rates due to increased occurrences of conditions such as hypertension, atherosclerosis, coronary artery disease, and diabetes compared to nonobese individuals. A patient is classified as obese if their actual body weight surpasses the ideal or desirable body weight by 20%, based on Metropolitan Life Insurance Company data. Ideal body weights consider average weights and heights for males and females...
303
01:23Dipeptidyl Peptidase 4 Inhibitors
770
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
770