Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis

• DOI: 10.1038/ncomms7498
• Publication Date: 2015-04-07T14:12:34Z
• Authors: Ji Miao; Alisha V. Ling; Praveen V. Manthena; Mary E. Gearing; Mark J. Graham; Rosanne M. Crooke; Kevin J. Croce; Ryan M. Esquejo; Clary B. Clish; ; Esther Torrecilla; Gumersindo Fernán...; Miguel A. Rubio; Lucio Cabrerizo; Ana Barabash; Andrés Sánchez Pe...; Antonio J. Torres; David Vicent; Sudha B. Biddinger
• Keywords: Hyperlipidemia; Trimethylamine N-oxide; Flavin-containing monooxygenase

Abstract Despite the well-documented association between insulin resistance and cardiovascular disease, key targets of relevant to development disease are not known. Here, using non-biased profiling methods, we identify enzyme flavin-containing monooxygenase 3 ( Fmo3 ) be a target insulin. FMO3 produces trimethylamine N-oxide (TMAO), which has recently been suggested promote atherosclerosis in mice humans. We show that is suppressed by vitro , increased obese/insulin resistant male obese/insulin-resistant Knockdown insulin-resistant suppresses FoxO1, central node for metabolic control, entirely prevents hyperglycaemia, hyperlipidemia atherosclerosis. Taken together, these data indicate required FoxO1 expression dysfunction.