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Pro-inflammatory, Building cholesterol plaques
- trimethylamine N-oxide (TMAO) is risk indicator for cardiovascular diseases, diabetes mellitus, nonalcoholic fatty liver disease, and other metabolic events. As the end-product of dietary choline and L-carnitine, TMAO is converted from trimethylamine (TMA) in the liver by flavin-containing monooxygenases (FMOs), especially FMO3.
- TMAO promotes the release of the inflammatory cytokines IL-1β and IL-18 via activation of the NLRP3 inflammasome from foetal human colon cells in a time- and dose-dependent manner
TMAO induces inflammation by activating the ROS-TXNIP-NLRP3 inflammasome, thereby contributing to endothelial dysfunction in human umbilical vein endothelial cells
- injection of TMAO was shown to significantly increase inflammatory markers, including cyclooxygenase 2, IL-6, E-selectin, and ICAM1, through the MAPK and NF-κB signalling pathways, which then recruit leukocytes and induce vascular inflammation.
- TMAO aggravates triglyceride accumulation and lipogenesis in the livers of high-fat diet-fed mice.
-TMAO promotes vascular endothelial cell pyroptosis via ROS production, thus resulting in the development of atherosclerosis
- Gut microbe-dependent metabolite, produced from degradation of choline and L-carnitine
- TMAO is asociated with platelet hyperactivity, lipid disorders, and oxidative stress
- Regardless of the initial TMAO levels, 10-year increases in TMAO from the first to second blood collection were significantly associated with an increased risk of CHD
- Patients with MCI and AD also show higher levels of gut microbiota-derived trimethylamine N-oxide (TMAO) in the cerebrospinal fluid.
- TMAO correlate with AD biomarkers including pTau, total Tau, and Aβ42.
- TMAO treatment reduces cognitive function and aging signs in mice, by ameliorating neuronal senescence and mitochondrial dysfunction.
- TMAO and its precursors have inflammatory biomarkers, possibly contributing to AD-related leaky gut.
- - The Western diet consists of low-fiber, high-fat, and high-protein foods, where it is common to eat fatty red meats and eggs that are rich in TMA and choline, thus increase TMAO production.
- TMA and subsequent conversion to TMAO by host FMO3 is related to T2DM pathogenesis and comorbidities.
- Mice with selective hepatic insulin resistance have elevated levels of circulating TMAO.
- Dietary supplementation with TMAO can exacerbate glucose intolerance in high-fat–fed mice.
- High concentrations TMAO directly binds to and activates PERK, a key effector of the unfolded protein response in the liver, promoting hyperglycemia and metabolic dysfunction
- - TMAO was found to contribute to thrombotic events by causing platelet hyperactivity
- [1.1] The Gut Microbial Endocrine Organ in Type 2 Diabetes  [Review]  [Best Practice & Research Clinical Endocrinology & Metabolism] [Journal]
- [1.2] Intestinal microbiota and diabetic kidney diseases: role of microbiota and derived metabolites in the modulation of renal inflammation and disease progression  [Review]  [ScienceDirect] [Journal]
- [1.3] Role of Gut Microbiota and Their Metabolites on Atherosclerosis, Hypertension and Human Blood Platelet Function: A Review  [Review]  [Nutrients] [Journal]
- [1.4] Long-Term Changes in Gut Microbial Metabolite Trimethylamine N-Oxide and Coronary Heart Disease Risk  [Review]  [Journal of the American College of Cardiology] [Journal]
- [1.5] Diet-Microbiota-Brain Axis in Alzheimer’s Disease  [Review]  [Annals of Nutrition and Metabolism] [Journal]