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Trimethylamine N -Oxide : A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function
- Source :
- Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona, International Journal of Molecular Sciences, Vol 19, Iss 10, p 3228 (2018)
- Publication Year :
- 2018
-
Abstract
- Altres ajuts: grant 12/C/2015 from La Fundació la Marató TV3 (to F.B.-V.). Recent evidence, including massive gene-expression analysis and a wide-variety of other multi-omics approaches, demonstrates an interplay between gut microbiota and the regulation of plasma lipids. Gut microbial metabolism of choline and -carnitine results in the formation of trimethylamine (TMA) and concomitant conversion into trimethylamine- N -oxide (TMAO) by liver flavin monooxygenase 3 (FMO3). The plasma level of TMAO is determined by the genetic variation, diet and composition of gut microbiota. Multiple studies have demonstrated an association between TMAO plasma levels and the risk of atherothrombotic cardiovascular disease (CVD). We aimed to review the molecular pathways by which TMAO production and FMO3 exert their proatherogenic effects. TMAO may promote foam cell formation by upregulating macrophage scavenger receptors, deregulating enterohepatic cholesterol and bile acid metabolism and impairing macrophage reverse cholesterol transport (RCT). Furthermore, FMO3 may promote dyslipidemia by regulating multiple genes involved in hepatic lipogenesis and gluconeogenesis. FMO3 also impairs multiple aspects of cholesterol homeostasis, including transintestinal cholesterol export and macrophage-specific RCT. At least part of these FMO3-mediated effects on lipid metabolism and atherogenesis seem to be independent of the TMA/TMAO formation. Overall, these findings have the potential to open a new era for the therapeutic manipulation of the gut microbiota to improve CVD risk.
- Subjects :
- 0301 basic medicine
intestinal microbiota
medicine.medical_specialty
Intestinal microbiota
Trimethylamine N-oxide
atherosclerosis and cardiovascular disease
030204 cardiovascular system & hematology
Gut flora
Atherosclerosis and cardiovascular disease
trimethylamine-N-oxide
Catalysis
cholesterol homeostasis
Inorganic Chemistry
lcsh:Chemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Choline
Trimethylamine
Trimethylamine- N -oxide
Cholesterol homeostasis
Physical and Theoretical Chemistry
Scavenger receptor
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Foam cell
biology
Cholesterol
Organic Chemistry
Reverse cholesterol transport
FMO3
Lipid metabolism
General Medicine
biology.organism_classification
Computer Science Applications
reverse cholesterol transport
030104 developmental biology
Endocrinology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
trimethylamine
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona, International Journal of Molecular Sciences, Vol 19, Iss 10, p 3228 (2018)
- Accession number :
- edsair.doi.dedup.....20fe22e6fa1779947b7a7361bc1800b0