RT Journal Article
T1 Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis
A1 Miao, Ji
A1 Rubio Herrera, Miguel Ángel
A1 Cabrerizo García, Lucio
A1 Barabash Bustelo, Ana
A1 Sánchez Pernaute, Andrés
A1 Torres García, Antonio José
A1 Biddinger, Sudha
AB Despite the well-documented association between insulin resistance and cardiovascular disease, the key targets of insulin relevant to the development of cardiovascular disease are not known. Here, using non-biased profiling methods, we identify the enzyme flavin-containing monooxygenase 3 (Fmo3) to be a target of insulin. FMO3 produces trimethylamine N-oxide (TMAO), which has recently been suggested to promote atherosclerosis in mice and humans. We show that FMO3 is suppressed by insulin in vitro, increased in obese/insulin resistant male mice and increased in obese/insulin-resistant humans. Knockdown of FMO3 in insulin-resistant mice suppresses FoxO1, a central node for metabolic control, and entirely prevents the development of hyperglycaemia, hyperlipidemia and atherosclerosis. Taken together, these data indicate that FMO3 is required for FoxO1 expression and the development of metabolic dysfunction.
SN 2041-1723
YR 2015
FD 2015-04-07
LK https://hdl.handle.net/20.500.14352/116876
UL https://hdl.handle.net/20.500.14352/116876
LA eng
NO Miao J, Ling AV, Manthena PV, Gearing ME, Graham MJ, Crooke RM, Croce KJ, Esquejo RM, Clish CB; Morbid Obesity Study Group; Vicent D, Biddinger SB. Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis. Nat Commun. 2015 Apr 7;6:6498. doi: 10.1038/ncomms7498. PMID: 25849138; PMCID: PMC4391288.
DS Docta Complutense
RD 24 abr 2025