Metabolomic and transcriptomic analyses of Fmo5-/- mice reveal roles for flavin-containing monooxygenase 5 (FMO5) in NRF2-mediated oxidative stress, the unfolded protein response, lipid homeostasis, and carbohydrate and one-carbon metabolism

Abstract

Flavin-containing monooxygenase 5 (FMO5) is a member of the FMO family of proteins best 28 known for their roles in the detoxification of foreign chemicals and more recently in 29 endogenous metabolism. We have previously shown that Fmo5-/- mice display an age-related 30 lean phenotype, with much reduced weight gain from 20 weeks of age. The phenotype is 31 characterized by decreased fat deposition, lower plasma concentrations of glucose and 32 cholesterol, higher glucose tolerance and insulin sensitivity, and resistance to diet-induced 33 obesity. In the present study we report the use of metabolomic and transcriptomic analyses of 34 livers of Fmo5-/- and wild-type mice to identify factors underlying the lean phenotype of 35 Fmo5-/- mice and gain insights into the function of FMO5.