ArticleJCI insight2023
Aorta- and liver-generated TMAO enhances trained immunity for increased inflammation via ER stress/mitochondrial ROS/glycolysis pathways.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
98 citing papers in PubMed, 120 citations in OpenAlex.
- Gut microbiota shaping fatty liver disease progression.Life science alliance · 2027Review
- Review
- Hydrogen peroxide sensing and signaling in physiology and disease: implications for therapy.Signal transduction and targeted therapy · 2026Review
- Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026Review
- Trained Immunity as a Mechanistic Bridge Between Uremic Toxins, Atherosclerosis, and Vascular Calcification in Chronic Kidney Disease.Cardiovascular toxicology · 2026Review
- Integrative Omics Analysis Reveals a CD206Barrier immunity · 2026Article
- A genome-wide Mendelian randomization study focusing on endoplasmic reticulum stress reveals novel genetic markers for renal cell carcinoma.Oncology letters · 2026Article
- An Update and Overview of the Ocular and Extraocular Microbiome and Its Impact on Ophthalmic Care.Advances in therapy · 2026Review
- β-cell FMO3-produced TMAO prevents NF-κB-mediated senescence and inflammation in ageing and diabetic conditions.Nature communications · 2026Article
- Clonal Hematopoiesis and Gut Microbiota-Derived TMAO as Candidate Amplifiers of Cardiovascular Inflammation: The CHIDT Hypothesis.Antioxidants (Basel, Switzerland) · 2026Review
- Trained immunity modulators: A new frontier in immunoregulation and disease intervention.Journal of advanced research · 2026Review
- A new paradigm: 46 structural cell types function as environment-supporting innate immune cells, with endothelial and vascular smooth muscle cells as key prototypes.iNew medicine · 2026Article
- Novel Organelle-Based Intracellular Immunity with Mechanistic and Therapeutic Implications.Barrier immunity · 2026Article
- The Gut-Adipose-Tumor Axis in Obesity-Related Cancer.Nutrients · 2026Review
- TMAO Induced Kidney Aging by Activating ZBP1-Mediated Necroptosis.Physiological research · 2026Article
- Multiomics: the intersection of personalized nutrition in cardiometabolic diseases.Journal of translational medicine · 2026Review
- Exploring the basis of Traditional Chinese Medicine in treating cardiovascular disease: insights into the microbiota-gut-heart axis.Chinese medicine · 2026Review
- Exercise training mitigates age-related cognitive decline by attenuating TMAO-induced inflammation.Scientific reports · 2026Article
- The multiple roles of Ggt1-Cre in the generation of transgenic mice.Cellular & molecular biology letters · 2026Article
- Reduced R-loop abundance at proinflammatory loci: a shared epigenetic mechanism in inflammatory and metabolic diseases.Frontiers in cardiovascular medicine · 2026Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
We determined whether gut microbiota-produced trimethylamine (TMA) is oxidized into trimethylamine N-oxide (TMAO) in nonliver tissues and whether TMAO promotes inflammation via trained immunity (TI). We found that endoplasmic reticulum (ER) stress genes were coupregulated with MitoCarta genes in chronic kidney diseases (CKD); TMAO upregulated 190 genes in human aortic endothelial cells (HAECs); TMAO synthesis enzyme flavin-containing monooxygenase 3 (FMO3) was expressed in human and mouse aortas; TMAO transdifferentiated HAECs into innate immune cells; TMAO phosphorylated 12 kinases in cytosol via its receptor PERK and CREB, and integrated with PERK pathways; and PERK inhibitors suppressed TMAO-induced ICAM-1. TMAO upregulated 3 mitochondrial genes, downregulated inflammation inhibitor DARS2, and induced mitoROS, and mitoTEMPO inhibited TMAO-induced ICAM-1. β-Glucan priming, followed by TMAO restimulation, upregulated TNF-α by inducing metabolic reprogramming, and glycolysis inhibitor suppressed TMAO-induced ICAM-1. Our results have provided potentially novel insights regarding TMAO roles in inducing EC activation and innate immune transdifferentiation and inducing metabolic reprogramming and TI for enhanced vascular inflammation, and they have provided new therapeutic targets for treating cardiovascular diseases (CVD), CKD-promoted CVD, inflammation, transplantation, aging, and cancer.
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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.