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The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509511/ https://www.ncbi.nlm.nih.gov/pubmed/26049045 http://dx.doi.org/10.1016/j.bcp.2015.05.013 |
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author | 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. Shephard, Elizabeth A. |
author_facet | 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. Shephard, Elizabeth A. |
author_sort | Gonzalez Malagon, Sandra G. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4509511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45095112015-08-01 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. Shephard, Elizabeth A. Biochem Pharmacol Article 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. Elsevier Science 2015-08-01 /pmc/articles/PMC4509511/ /pubmed/26049045 http://dx.doi.org/10.1016/j.bcp.2015.05.013 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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. Shephard, Elizabeth A. The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing |
title | The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing |
title_full | The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing |
title_fullStr | The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing |
title_full_unstemmed | The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing |
title_short | The phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing |
title_sort | phenotype of a knockout mouse identifies flavin-containing monooxygenase 5 (fmo5) as a regulator of metabolic ageing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509511/ https://www.ncbi.nlm.nih.gov/pubmed/26049045 http://dx.doi.org/10.1016/j.bcp.2015.05.013 |
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