Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function
Por:
Canyelles, M, Tondo, M, Cedo, L, Farras, M, Escola-Gil, JC, Blanco-Vaca, F
Publicada:
1 oct 2018
Resumen:
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 l-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.
Filiaciones:
Canyelles, M:
Hosp Santa Creu & Sant Pau, Serv Bioquim, Inst Invest Biomed IIB St Pau, Barcelona 08041, Spain
Tondo, M:
Hosp Santa Creu & Sant Pau, Serv Bioquim, Inst Invest Biomed IIB St Pau, Barcelona 08041, Spain
Cedo, L:
Hosp Santa Creu & Sant Pau, Inst Recerca, Inst Invest Biomed IIB St Pau, Barcelona 08025, Spain
CIBER Diabet & Enfermedades Metab Asociadas CIBER, Barcelona 08907, Spain
Farras, M:
Hosp Santa Creu & Sant Pau, Inst Recerca, Inst Invest Biomed IIB St Pau, Barcelona 08025, Spain
ISCIII, CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Barcelona 08003, Spain
Escola-Gil, JC:
Hosp Santa Creu & Sant Pau, Inst Recerca, Inst Invest Biomed IIB St Pau, Barcelona 08025, Spain
CIBER Diabet & Enfermedades Metab Asociadas CIBER, Barcelona 08907, Spain
Blanco-Vaca, F:
Hosp Santa Creu & Sant Pau, Serv Bioquim, Inst Invest Biomed IIB St Pau, Barcelona 08041, Spain
CIBER Diabet & Enfermedades Metab Asociadas CIBER, Barcelona 08907, Spain
Univ Autonoma Barcelona, Dept Bioquim Biol Mol & Biomed, E-08193 Barcelona, Spain
Gold, Green Published
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