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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
- 1.4 (1)
- 1.5 (2)
Shared Reference Notes
- 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
- A high-fat diet is associated with the occurrence of microbes that catabolize choline and the accumulation of trimethylamine N-oxide (TMAO) in the bloodstream, a contributing factor for heart disease.
- Choline > Elevated plasma levels of the gut microbe-dependent metabolite TMAO > predict incident risk for CVD development independent of traditional risk factors.
- Chronic dietary red meat > increases systemic TMAO levels through: (i) enhanced dietary precursors; (ii) increased microbial TMA/TMAO production from carnitine, but not choline; and (iii) reduced renal TMAO excretion.
- Discontinuation of dietary red meat reduces plasma TMAO within 4 weeks.
- - protein-supplemented group without exercise > increases in trimethylamine-N-oxide (TMAO) and phenylacetylglycine (PAG).
- In contrast, the addition of exercise decreases TMAO
- - Fish > rich in preformed TMAO > greatest impact on circulating TMAO concentrations; however, fish intake is associated with decreased risk of cardiovascular disease
- Serum TMAO levels in AD/CRC patients are higher than those in healthy people, and its concentrations may be positively correlated with AD/cancer progression
- TMAO is the hepatic oxidation product of the microbial trimethylamine (TMA).
- dietary supplementation with TMAO was shown to promote atherogenesis and development of atherosclerosis in mice.
- TMAO levels associate with an increased risk of adverse cardiovascular events.
- Carotid atherosclerosis was demonstrated to be associated with gut microbial metabolites (especially TMAO and p-cresol sulfate) in >3,000 patients, which could serve as an independent predictor of the disease.
- - TMAO levels are also associated with heart failure and coronary artery disease.
- TMAO enhances the responsiveness of platelets to multiple agonists, promoting platelet hyperactivity and thus thrombosis and subsequent cardiovascular disease.
- - Bilophila, a genus of gut microbes, can metabolize TMA, resulting in lower TMAO,58 suggesting that differences in TMA-metabolizing gut bacteria in individuals lead to different ultimate effects, and replacement of relevant bacteria may reduce the risk from TMAO.
- A shift in the metabolic function of intestinal bacteria is predominantly caused by dysbiosis. In the intestine, it leads to an increase in the permeability of intestinal mucosa for LPS and ultimately causes chronic inflammation. Concentration of bacterial metabolites in the blood, such as trimethylamine which is metabolized in the liver to trimethylamine-N-oxide (TMAO) correlates with the severity of steatohepatitis