Effect of Differences in the Microbiome of <i>Cyp17a1</i>-Deficient Mice on Atherosclerotic Background
CYP17A1 is a cytochrome P450 enzyme that has 17-alpha-hydroxylase and C17,20-lyase activities. <i>Cyp17a11</i> deficiency is associated with high body mass and visceral fat deposition in atherosclerotic female ApoE knockout (KO, d/d or −/−) mice. In the present study, we aimed to investi...
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doaj-e7bbdff2fb514f07bcda05412fa985ad2021-06-01T00:51:02ZengMDPI AGCells2073-44092021-05-01101292129210.3390/cells10061292Effect of Differences in the Microbiome of <i>Cyp17a1</i>-Deficient Mice on Atherosclerotic BackgroundAxel Künstner0Redouane Aherrahrou1Misa Hirose2Petra Bruse3Saleh Mohamed Ibrahim4Hauke Busch5Jeanette Erdmann6Zouhair Aherrahrou7Medical Systems Biology Group, Lübeck Institute for Experimental Dermatology, University of Lübeck, 23562 Lübeck, GermanyInstitute for Cardiogenetics, University of Lübeck, 23562 Lübeck, GermanyLübeck Institute for Experimental Dermatology, University of Lübeck, 23562 Lübeck, GermanyInstitute for Cardiogenetics, University of Lübeck, 23562 Lübeck, GermanyLübeck Institute for Experimental Dermatology, University of Lübeck, 23562 Lübeck, GermanyMedical Systems Biology Group, Lübeck Institute for Experimental Dermatology, University of Lübeck, 23562 Lübeck, GermanyInstitute for Cardiogenetics, University of Lübeck, 23562 Lübeck, GermanyInstitute for Cardiogenetics, University of Lübeck, 23562 Lübeck, GermanyCYP17A1 is a cytochrome P450 enzyme that has 17-alpha-hydroxylase and C17,20-lyase activities. <i>Cyp17a11</i> deficiency is associated with high body mass and visceral fat deposition in atherosclerotic female ApoE knockout (KO, d/d or −/−) mice. In the present study, we aimed to investigate the effects of diet and <i>Cyp17a1</i> genotype on the gut microbiome. Female <i>Cyp17a1</i> (d/d) × ApoE (d/d) (DKO) and ApoE (d/d) (controls) were fed either standard chow or a Western-type diet (WTD), and we demonstrated the effects of genetics and diet on the body mass of the mice and composition of their gut microbiome. We found a significantly lower alpha diversity after accounting for the ecological network structure in DKO mice and WTD-fed mice compared with chow-fed ApoE(d/d). Furthermore, we found a strong significant positive association of the <i>Firmicutes</i> vs. <i>Bacteroidota</i> ratio with body mass and the circulating total cholesterol and triglyceride concentrations of the mice when feeding the WTD, independent of the <i>Cyp17a1</i> genotype. Further pathway enrichment and network analyses revealed a substantial effect of <i>Cyp17a1</i> genotype on associated cardiovascular and obesity-related pathways involving aspartate and L-arginine. Future studies are required to validate these findings and further investigate the role of aspartate/L-arginine pathways in the obesity and body fat distribution in our mouse model.https://www.mdpi.com/2073-4409/10/6/1292Cyp17a1mouseknockoutmicrobiotaobesitydisorders of sex development |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Axel Künstner Redouane Aherrahrou Misa Hirose Petra Bruse Saleh Mohamed Ibrahim Hauke Busch Jeanette Erdmann Zouhair Aherrahrou |
spellingShingle |
Axel Künstner Redouane Aherrahrou Misa Hirose Petra Bruse Saleh Mohamed Ibrahim Hauke Busch Jeanette Erdmann Zouhair Aherrahrou Effect of Differences in the Microbiome of <i>Cyp17a1</i>-Deficient Mice on Atherosclerotic Background Cells Cyp17a1 mouse knockout microbiota obesity disorders of sex development |
author_facet |
Axel Künstner Redouane Aherrahrou Misa Hirose Petra Bruse Saleh Mohamed Ibrahim Hauke Busch Jeanette Erdmann Zouhair Aherrahrou |
author_sort |
Axel Künstner |
title |
Effect of Differences in the Microbiome of <i>Cyp17a1</i>-Deficient Mice on Atherosclerotic Background |
title_short |
Effect of Differences in the Microbiome of <i>Cyp17a1</i>-Deficient Mice on Atherosclerotic Background |
title_full |
Effect of Differences in the Microbiome of <i>Cyp17a1</i>-Deficient Mice on Atherosclerotic Background |
title_fullStr |
Effect of Differences in the Microbiome of <i>Cyp17a1</i>-Deficient Mice on Atherosclerotic Background |
title_full_unstemmed |
Effect of Differences in the Microbiome of <i>Cyp17a1</i>-Deficient Mice on Atherosclerotic Background |
title_sort |
effect of differences in the microbiome of <i>cyp17a1</i>-deficient mice on atherosclerotic background |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2021-05-01 |
description |
CYP17A1 is a cytochrome P450 enzyme that has 17-alpha-hydroxylase and C17,20-lyase activities. <i>Cyp17a11</i> deficiency is associated with high body mass and visceral fat deposition in atherosclerotic female ApoE knockout (KO, d/d or −/−) mice. In the present study, we aimed to investigate the effects of diet and <i>Cyp17a1</i> genotype on the gut microbiome. Female <i>Cyp17a1</i> (d/d) × ApoE (d/d) (DKO) and ApoE (d/d) (controls) were fed either standard chow or a Western-type diet (WTD), and we demonstrated the effects of genetics and diet on the body mass of the mice and composition of their gut microbiome. We found a significantly lower alpha diversity after accounting for the ecological network structure in DKO mice and WTD-fed mice compared with chow-fed ApoE(d/d). Furthermore, we found a strong significant positive association of the <i>Firmicutes</i> vs. <i>Bacteroidota</i> ratio with body mass and the circulating total cholesterol and triglyceride concentrations of the mice when feeding the WTD, independent of the <i>Cyp17a1</i> genotype. Further pathway enrichment and network analyses revealed a substantial effect of <i>Cyp17a1</i> genotype on associated cardiovascular and obesity-related pathways involving aspartate and L-arginine. Future studies are required to validate these findings and further investigate the role of aspartate/L-arginine pathways in the obesity and body fat distribution in our mouse model. |
topic |
Cyp17a1 mouse knockout microbiota obesity disorders of sex development |
url |
https://www.mdpi.com/2073-4409/10/6/1292 |
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