ArticleProceedings of the National Academy of Sciences of the United States of America2020
Retinol binding protein 4 primes the NLRP3 inflammasome by signaling through Toll-like receptors 2 and 4.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 88 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- RBP4-a risk factor in lipid metabolism-serves as an early diagnostic and prognostic marker of knee osteoarthritis progression.Arthritis research & therapy · 2026Article
- Proteomics of human duodenum in pre-diabetes and type 2 diabetes reveals potential novel therapeutic targets for aetiology and therapeutics.Clinical proteomics · 2026Article
- Proteomic Insights into Venous Thromboembolism.Medical sciences (Basel, Switzerland) · 2026Review
- Article
- Hepatokines and polycystic ovary syndrome: investigating the connection between the hepato-ovarian axis and disorders in glycolipid metabolism in PCOS: a narrative review.Frontiers in endocrinology · 2026Review
- Beyond a gatekeeper: the non-classical signaling role of STRA6 in driving endothelial senescence and atherosclerosis.Frontiers in immunology · 2026Review
- Retinol Binding Protein 4 and Uric Acid as Risk Factors for Insulin Resistance in Type 2 Diabetes Mellitus.Journal of diabetes research · 2026Article
- Retinol-binding protein 4 in cardiovascular diseases: mechanisms and therapeutic perspectives.Frontiers in cardiovascular medicine · 2026Review
- How Adipocytes Orchestrate Inflammation Within Adipose Tissue?Biomolecules · 2025Review
- Adipokines and Vascular Modulators in CKM: Emerging Biomarkers as Diagnostic and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Naringin inhibits the osteoblast-osteoclast pyroptosis cascade reaction mediated by accumulated bone marrow adipose tissue in the treatment of postmenopausal osteoporosis.Journal of orthopaedic translation · 2025Article
- Bioinformatics analyses of comorbid mechanisms between psoriasis and type 2 diabetes mellitus.Scientific reports · 2025Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Retinol Binding Protein 4 reactivates latent HIV-1 by triggering canonical NF-κB, JAK/STAT5 and JNK signalling.Signal transduction and targeted therapy · 2025Article
- Retinol binding protein 4 enhances cellular cholesterol uptake to facilitate influenza A virus infection.PLoS pathogens · 2025Article
- The Potential Role of Retinol-Binding Protein 4 in Heart Failure: A Review.Reviews in cardiovascular medicine · 2025Review
- The role of inflammatory biomarkers RBP4, Lipocalin-2, and hsCRP in prediabetes and type 2 diabetes mellitus.Journal of medical biochemistry · 2025Article
- Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- Differential proteomic profiles between cognitive frail and robust older adults from the MELoR cohort.GeroScience · 2025Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Adipose tissue (AT) inflammation contributes to systemic insulin resistance. In obesity and type 2 diabetes (T2D), retinol binding protein 4 (RBP4), the major retinol carrier in serum, is elevated in AT and has proinflammatory effects which are mediated partially through Toll-like receptor 4 (TLR4). We now show that RBP4 primes the NLRP3 inflammasome for interleukin-1β (IL1β) release, in a glucose-dependent manner, through the TLR4/MD2 receptor complex and TLR2. This impairs insulin signaling in adipocytes. IL1β is elevated in perigonadal white AT (PGWAT) of chow-fed RBP4-overexpressing mice and in serum and PGWAT of high-fat diet-fed RBP4-overexpressing mice vs. wild-type mice. Holo- or apo-RBP4 injection in wild-type mice causes insulin resistance and elevates PGWAT inflammatory markers, including IL1β. TLR4 inhibition in RBP4-overexpressing mice reduces PGWAT inflammation, including IL1β levels and improves insulin sensitivity. Thus, the proinflammatory effects of RBP4 require NLRP3-inflammasome priming. These studies may provide approaches to reduce AT inflammation and insulin resistance in obesity and diabetes.
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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.