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Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria

We have previously identified flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic aging. The aim of the present study was to investigate the role of FMO5 in glucose homeostasis and the impact of diet and gut flora on the phenotype of mice in which the Fmo5 gene has been disrupted (F...

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Autores principales: Scott, Flora, Gonzalez Malagon, Sandra G., O’Brien, Brett A., Fennema, Diede, Veeravalli, Sunil, Coveney, Clarissa R., Phillips, Ian R., Shephard, Elizabeth A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Pharmacology and Experimental Therapeutics 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539585/
https://www.ncbi.nlm.nih.gov/pubmed/28646079
http://dx.doi.org/10.1124/dmd.117.076612
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author Scott, Flora
Gonzalez Malagon, Sandra G.
O’Brien, Brett A.
Fennema, Diede
Veeravalli, Sunil
Coveney, Clarissa R.
Phillips, Ian R.
Shephard, Elizabeth A.
author_facet Scott, Flora
Gonzalez Malagon, Sandra G.
O’Brien, Brett A.
Fennema, Diede
Veeravalli, Sunil
Coveney, Clarissa R.
Phillips, Ian R.
Shephard, Elizabeth A.
author_sort Scott, Flora
collection PubMed
description We have previously identified flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic aging. The aim of the present study was to investigate the role of FMO5 in glucose homeostasis and the impact of diet and gut flora on the phenotype of mice in which the Fmo5 gene has been disrupted (Fmo5(−)(/)(−) mice). In comparison with wild-type (WT) counterparts, Fmo5(−)(/)(−) mice are resistant to age-related changes in glucose homeostasis and maintain the higher glucose tolerance and insulin sensitivity characteristic of young animals. When fed a high-fat diet, they are protected against weight gain and reduction of insulin sensitivity. The phenotype of Fmo5(−)(/)(−) mice is independent of diet and the gut microbiome and is determined solely by the host genotype. Fmo5(−)(/)(−) mice have metabolic characteristics similar to those of germ-free mice, indicating that FMO5 plays a role in sensing or responding to gut bacteria. In WT mice, FMO5 is present in the mucosal epithelium of the gastrointestinal tract where it is induced in response to a high-fat diet. In comparison with WT mice, Fmo5(−)(/)(−) mice have fewer colonic goblet cells, and they differ in the production of the colonic hormone resistin-like molecule β. Fmo5(−)(/)(−) mice have lower concentrations of tumor necrosis factor α in plasma and of complement component 3 in epididymal white adipose tissue, indicative of improved inflammatory tone. Our results implicate FMO5 as a regulator of body weight and of glucose disposal and insulin sensitivity and, thus, identify FMO5 as a potential novel therapeutic target for obesity and insulin resistance.
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spelling pubmed-55395852017-09-01 Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria Scott, Flora Gonzalez Malagon, Sandra G. O’Brien, Brett A. Fennema, Diede Veeravalli, Sunil Coveney, Clarissa R. Phillips, Ian R. Shephard, Elizabeth A. Drug Metab Dispos Articles We have previously identified flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic aging. The aim of the present study was to investigate the role of FMO5 in glucose homeostasis and the impact of diet and gut flora on the phenotype of mice in which the Fmo5 gene has been disrupted (Fmo5(−)(/)(−) mice). In comparison with wild-type (WT) counterparts, Fmo5(−)(/)(−) mice are resistant to age-related changes in glucose homeostasis and maintain the higher glucose tolerance and insulin sensitivity characteristic of young animals. When fed a high-fat diet, they are protected against weight gain and reduction of insulin sensitivity. The phenotype of Fmo5(−)(/)(−) mice is independent of diet and the gut microbiome and is determined solely by the host genotype. Fmo5(−)(/)(−) mice have metabolic characteristics similar to those of germ-free mice, indicating that FMO5 plays a role in sensing or responding to gut bacteria. In WT mice, FMO5 is present in the mucosal epithelium of the gastrointestinal tract where it is induced in response to a high-fat diet. In comparison with WT mice, Fmo5(−)(/)(−) mice have fewer colonic goblet cells, and they differ in the production of the colonic hormone resistin-like molecule β. Fmo5(−)(/)(−) mice have lower concentrations of tumor necrosis factor α in plasma and of complement component 3 in epididymal white adipose tissue, indicative of improved inflammatory tone. Our results implicate FMO5 as a regulator of body weight and of glucose disposal and insulin sensitivity and, thus, identify FMO5 as a potential novel therapeutic target for obesity and insulin resistance. The American Society for Pharmacology and Experimental Therapeutics 2017-09 2017-09 /pmc/articles/PMC5539585/ /pubmed/28646079 http://dx.doi.org/10.1124/dmd.117.076612 Text en Copyright © 2017 by The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the CC BY Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Articles
Scott, Flora
Gonzalez Malagon, Sandra G.
O’Brien, Brett A.
Fennema, Diede
Veeravalli, Sunil
Coveney, Clarissa R.
Phillips, Ian R.
Shephard, Elizabeth A.
Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria
title Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria
title_full Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria
title_fullStr Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria
title_full_unstemmed Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria
title_short Identification of Flavin-Containing Monooxygenase 5 (FMO5) as a Regulator of Glucose Homeostasis and a Potential Sensor of Gut Bacteria
title_sort identification of flavin-containing monooxygenase 5 (fmo5) as a regulator of glucose homeostasis and a potential sensor of gut bacteria
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539585/
https://www.ncbi.nlm.nih.gov/pubmed/28646079
http://dx.doi.org/10.1124/dmd.117.076612
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