Suppression of trimethylamine N-oxide with DMB mitigates vascular dysfunction, exercise intolerance, and frailty associated with a Western-style diet in mice
Vienna E. Brunt, Nathan Greenberg, Zachary J. Sapinsley, Abigail G. Casso, James J. Richey, Nicholas S. VanDongen, Rachel A. Gioscia‐Ryan, Brian P. Ziemba, Andrew P. Neilson, Kevin P. Davy, Douglas R. Seals
Abstract
We provide novel evidence that increased circulating concentrations of the gut microbiome-derived metabolite trimethylamine N-oxide (TMAO) contribute to vascular dysfunction associated with consumption of a Western-style diet and that this dysfunction can be prevented by suppressing TMAO with DMB, thereby supporting translation of this compound to humans. Furthermore, to our knowledge, we present the first evidence of the role of TMAO in mediating impairments in endurance exercise tolerance and increased frailty in any context.
Topics & Concepts
Endothelial dysfunctionInternal medicineEndocrinologyTrimethylamine N-oxideMedicineOxidative stressArterial stiffnessEndotheliumChemistryBlood pressureTrimethylamineBiochemistryNutritional Studies and DietDiet and metabolism studiesCardiovascular Health and Risk Factors