ArticlePloS one2015
Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Endothelial TLR4 at the Crossroads of Vascular Senescence and Targeted Senotherapeutics.Aging cell · 2026Review
- Toll Like Receptor 4: A Potential Link Between Obesity and Metabolic Diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Linking inflammation, metabolic dysfunction, and neurodegeneration: a comprehensive review of TLR2 pathways in type 2 diabetes.Frontiers in clinical diabetes and healthcare · 2026Review
- Taking its TOLL: the role of toll-like receptor 4 in human health and disease, and its potential as a therapeutic target.Frontiers in immunology · 2026Review
- Microglia/macrophage-specific deletion of TLR-4 protects against neural effects of diet-induced obesity in a sexually dimorphic manner.Journal of neuroinflammation · 2025Article
- Hepatocyte-specific RIG-I loss attenuates metabolic dysfunction-associated steatotic liver disease in mice via changes in mitochondrial respiration and metabolite profiles.Toxicological research · 2024Article
- The Association between Tooth Loss and Insulin Resistance Mediated by Diet Quality and Systemic Immunoinflammatory Index.Nutrients · 2023Article
- Comprehensive Physicochemical Characterization, In Vitro Membrane Permeation, and In Vitro Human Skin Cell Culture of a Novel TOPK Inhibitor, HI-TOPK-032.International journal of molecular sciences · 2023Article
- Innovative Rocuronium Bromide Topical Formulation for Targeted Skin Drug Delivery: Design, Comprehensive Characterization, In Vitro 2D/3D Human Cell Culture and Permeation.International journal of molecular sciences · 2023Article
- Immunometabolism in type 2 diabetes mellitus: tissue-specific interactions.Archives of medical science : AMS · 2023Article
- Effect of acute TLR4 inhibition on insulin resistance in humans.The Journal of clinical investigation · 2022Article
- Pathophysiological Commonality Between Irritable Bowel Syndrome and Metabolic Syndrome: Role of Corticotropin-releasing Factor-Toll-like Receptor 4-Proinflammatory Cytokine Signaling.Journal of neurogastroenterology and motility · 2022Review
- BMP-7 Attenuates Inflammation-Induced Pyroptosis and Improves Cardiac Repair in Diabetic Cardiomyopathy.Cells · 2021Article
- Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer's Disease.Frontiers in neuroscience · 2021Review
- Retinol binding protein 4 primes the NLRP3 inflammasome by signaling through Toll-like receptors 2 and 4.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Pattern Recognition Receptor-Mediated Chronic Inflammation in the Development and Progression of Obesity-Related Metabolic Diseases.Mediators of inflammation · 2019Review
- Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements.Cell metabolism · 2018Article
- Pathogenesis of NASH: The Impact of Multiple Pathways.Current hepatology reports · 2018Article
- TLR4 inhibitor TAK-242 attenuates the adverse neural effects of diet-induced obesity.Journal of neuroinflammation · 2018Article
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
aimsTo evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. MATERIALS AND
methodsFor the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp.
resultsAcute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP.
conclusionsPharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.