Skip navigation

The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing

The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing

Gonzalez Malagon, Sandra G., Melidoni, Anna N., Hernandez, Diana, Omar, Bilal A., Houseman, Lyndsey, Veeravalli, Sunil, Scott, Flora, Varshavi, Dorsa, Everett, Jeremy, Tsuchiya, Yugo, Timms, John F., Phillips, Ian R. and Shephard, Elizabeth A. (2015) The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing. Biochemical Pharmacology, 96 (3). pp. 267-277. ISSN 0006-2952 (doi:10.1016/j.bcp.2015.05.013)

[img] PDF (Author Accepted Manuscript with comments)
13664_EVERETT_BiochemPharm_(AAM_27May2015).pdf - Accepted Version
Restricted to Registered users only
Available under License Creative Commons Attribution.

Download (1MB)
[img] PDF (Author's accepted manuscript w/o comments)
13664_EVERETT_Gonzalez_et_al_final_submission_authors_BiochemPharm_(GOLD_OA)_(AAM_accepted___May2015_held_for_compliance).pdf - Accepted Version
Restricted to Registered users only
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (5MB)
[img] PDF (Publisher PDF)
13664_Everett_The phenotype of a knockout mouse (pub PDF OA) 2015.pdf - Published Version
Restricted to Registered users only
Available under License Creative Commons Attribution.

Download (1MB)
[img] PDF (Email of Acceptance)
13664_EVERETT_BiochemPharm_(Acceptance_email_May2015).pdf - Additional Metadata
Restricted to Repository staff only

Download (154kB)

Abstract

We report the production and metabolic phenotype of a mouse line in which the Fmo5 gene is disrupted. In comparison with wild-type (WT) mice, Fmo5−/− mice exhibit a lean phenotype, which is age-related, becoming apparent after 20 weeks of age. Despite greater food intake, Fmo5−/− mice weigh less, store less fat in white adipose tissue (WAT), have lower plasma glucose and cholesterol concentrations and enhanced whole-body energy expenditure, due mostly to increased resting energy expenditure, with no increase in physical activity. An increase in respiratory exchange ratio during the dark phase, the period in which the mice are active, indicates a switch from fat to carbohydrate oxidation. In comparison with WT mice, the rate of fatty acid oxidation in Fmo5−/− mice is higher in WAT, which would contribute to depletion of lipid stores in this tissue, and lower in skeletal muscle. Five proteins were down regulated in the liver of Fmo5−/− mice: aldolase B, ketohexokinase and cytosolic glycerol 3-phosphate dehydrogenase (GPD1) are involved in glucose or fructose metabolism and GPD1 also in production of glycerol 3-phosphate, a precursor of triglyceride biosynthesis; HMG-CoA synthase 1 is involved in cholesterol biosynthesis; and malic enzyme 1 catalyzes the oxidative decarboxylation of malate to pyruvate, in the process producing NADPH for use in lipid and cholesterol biosynthesis. Down regulation of these proteins provides a potential explanation for the reduced fat deposits and lower plasma cholesterol characteristic of Fmo5−/− mice. Our results indicate that disruption of the Fmo5 gene slows metabolic ageing via pleiotropic effects.

Item Type: Article
Additional Information: Open Access funded by Wellcome Trust for University College London (UCL) authors.
Uncontrolled Keywords: metabonomics, metabolic profiling, genetic knock-out, FMO5, body weight, cholesterol, glucose, malic enzyme 1, white adipose tissue,
Subjects: Q Science > QD Chemistry
Q Science > QR Microbiology
R Medicine > RS Pharmacy and materia medica
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Department of Pharmaceutical, Chemical & Environmental Sciences
Last Modified: 27 Apr 2017 17:21
Selected for GREAT 2016: GREAT a
Selected for GREAT 2017: GREAT a
Selected for GREAT 2018: None
URI: http://gala.gre.ac.uk/id/eprint/13664

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics