ArticleMediators of inflammation2020
TLR4/AP-1-Targeted Anti-Inflammatory Intervention Attenuates Insulin Sensitivity and Liver Steatosis.
Article in Mediators of inflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Trained immunity: New insights into pathogenesis and therapeutic targets in diabetes and diabetic complications.Genes & diseases · 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
- Epigenetic regulation and posttranslational modifications of FXR: underlying mechanisms and implications in digestive diseases.Acta pharmacologica Sinica · 2026Review
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- The insulin resistance-systemic vascular resistance-isolated diastolic hypertension axis: a metabolic framework for an overlooked hypertension phenotype.Frontiers in cardiovascular medicine · 2026Review
- Synergistic potential of Berberine and Wogonin improved adipose inflammation and insulin resistance associated with obesity through HIF-α axis.Chinese medicine · 2025Article
- Analysis of hemolysis-associated acute myeloid leukemia genes obtained using weighted gene co-expression network analysis and a Mendelian randomization study.Blood research · 2025Article
- Identification of genes involved in energy metabolism in preeclampsia and discovery of early biomarkers.Frontiers in immunology · 2025Article
- Nuclear receptor-driven immunometabolic crosstalk: immune-centric pharmacology targeting the inflamed nexus.Frontiers in cell and developmental biology · 2025Review
- Metabolomics uncovers the diabetes metabolic network: from pathophysiological mechanisms to clinical applications.Frontiers in endocrinology · 2025Review
- Dysregulation of c-Jun (JUN) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) in obese people and their predictive values for metabolic syndrome.Endocrine journal · 2024Article
- Navigating the Neuroimmunomodulation Frontier: Pioneering Approaches and Promising Horizons-A Comprehensive Review.International journal of molecular sciences · 2024Review
- Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis.Signal transduction and targeted therapy · 2024Article
- Rotundic acid improves nonalcoholic steatohepatitis in mice by regulating glycolysis and the TLR4/AP1 signaling pathway.Lipids in health and disease · 2023Article
- Unraveling the Mechanism of Immunity and Inflammation Related to Molecular Signatures Crosstalk Among Obesity, T2D, and AD: Insights From Bioinformatics Approaches.Bioinformatics and biology insights · 2023Article
- Vitamin D and Swimming Exercise Prevent Obesity in Rats under a High-Fat Diet via Targeting FATP4 and TLR4 in the Liver and Adipose Tissue.International journal of environmental research and public health · 2022Article
- Immune system modulation in aging: Molecular mechanisms and therapeutic targets.Frontiers in immunology · 2022Review
- Saturated fat ingestion stimulates proatherogenic inflammation in polycystic ovary syndrome.American journal of physiology. Endocrinology and metabolism · 2021Article
- Long Chain Fatty Acids as Modulators of Immune Cells Function: Contribution of FFA1 and FFA4 Receptors.Frontiers in physiology · 2021Review
- Andrographolide, an Anti-Inflammatory Multitarget Drug: All Roads Lead to Cellular Metabolism.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin resistance has been shown to be the common pathogenesis of many metabolic diseases. Metainflammation is one of the important characteristics of insulin resistance. Macrophage polarization mediates the production and development of metainflammation. Toll-like receptor 4 (TLR4) mediates macrophage activity and is probably the intersection of immunity and metabolism, but the detailed mechanism is probably not fully understood. Activated protein 1 (AP1) signaling pathway is very important in macrophage activation-mediated inflammation. However, it is unclear whether AP1 signaling pathway mediates metabolic inflammation in the liver. We aimed to investigate the effects of macrophage TLR4-AP1 signaling pathway on hepatocyte metabolic inflammation, insulin sensitivity, and lipid deposition, as well as to explore the potential of TLR4-AP1 as new intervention targets of insulin resistance and liver steatosis. TLR4 and AP1 were silenced in the RAW264.7 cells by lentiviral siRNA transfection. In vivo transduction of lentivirus was administered in mice fed with high-fat diet. Insulin sensitivity and inflammation were evaluated in the treated cells or animals. Our results indicated that TLR4/AP-1 siRNA transfection alleviated high-fat diet-induced systemic and hepatic inflammation, obesity, and insulin resistance in mice. Additionally, TLR4/AP-1 siRNA transfection mitigated palmitic acid- (PA-) induced inflammation in RAW264.7 cells and metabolic abnormalities in cocultured AML hepatocytes. Herein, we propose that TLR4-AP1 signaling pathway activation plays a crucial role in high fat- or PA-induced metabolic inflammation and insulin resistance in hepatocytes. Intervention of the TLR4 expression regulates macrophage polarization and metabolic inflammation and further alleviates insulin resistance and lipid deposition in hepatocytes.
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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.