Hormonal
Pharmacologic inhibition of hepatic FMO3 reduces circulating TMAO and atherosclerosis but simultaneously decreases plasma glucose, insulin, and lipids, indicating that FMO3 inhibition has broad metabolic effects beyond lipid/TMAO modulation.
Current research suggests that inhibiting the enzyme FMO3 might lower cardiovascular risk markers like TMAO and atherosclerosis, but it also significantly lowers blood sugar and insulin levels. This means that any potential therapeutic strategy targeting FMO3 must account for these broad metabolic changes, as it is not just a simple lipid or TMAO modulator. For now, this is a mechanistic finding in mice, not a human treatment protocol.
Knockdown of hepatic FMO3 in LDL receptor knockout mice using an antisense oligonucleotide resulted in decreased circulating TMAO levels and atherosclerosis. Surprisingly, we also observed significant decreases in hepatic lipids and in levels of plasma lipids, ketone bodies, glucose, and insulin.
Why this rating
Robust in vivo mouse models with multiple endpoints (TMAO, atherosclerosis, glucose, lipids) and in vitro validation, but translated to humans only via genetic association and mechanism inference.
Source
Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis
Diana M. Shih et al. · Journal of Lipid Research · 2014
DOI 10.1194/jlr.m051680
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