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Article

Effect of Differences in the Microbiome of Cyp17a1-Deficient Mice on Atherosclerotic Background

1
Medical Systems Biology Group, Lübeck Institute for Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany
2
Institute for Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany
3
Centre for Public Health Genomics, Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908-0717, USA
4
Lübeck Institute for Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany
5
College of Medicine and Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
6
DZHK (German Centre for Cardiovascular Research), University Heart Centre Lübeck, 23562 Lübeck, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Dimitris Kardassis
Cells 2021, 10(6), 1292; https://doi.org/10.3390/cells10061292
Received: 13 April 2021 / Revised: 12 May 2021 / Accepted: 19 May 2021 / Published: 23 May 2021
(This article belongs to the Special Issue Interplay of Gene Expression Regulation and Microbiome)
CYP17A1 is a cytochrome P450 enzyme that has 17-alpha-hydroxylase and C17,20-lyase activities. Cyp17a11 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 Cyp17a1 genotype on the gut microbiome. Female Cyp17a1 (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 Firmicutes vs. Bacteroidota ratio with body mass and the circulating total cholesterol and triglyceride concentrations of the mice when feeding the WTD, independent of the Cyp17a1 genotype. Further pathway enrichment and network analyses revealed a substantial effect of Cyp17a1 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. View Full-Text
Keywords: Cyp17a1; mouse; knockout; microbiota; obesity; disorders of sex development; coronary artery disease; myocardial infarction; atherosclerosis Cyp17a1; mouse; knockout; microbiota; obesity; disorders of sex development; coronary artery disease; myocardial infarction; atherosclerosis
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MDPI and ACS Style

Künstner, A.; Aherrahrou, R.; Hirose, M.; Bruse, P.; Ibrahim, S.M.; Busch, H.; Erdmann, J.; Aherrahrou, Z. Effect of Differences in the Microbiome of Cyp17a1-Deficient Mice on Atherosclerotic Background. Cells 2021, 10, 1292. https://doi.org/10.3390/cells10061292

AMA Style

Künstner A, Aherrahrou R, Hirose M, Bruse P, Ibrahim SM, Busch H, Erdmann J, Aherrahrou Z. Effect of Differences in the Microbiome of Cyp17a1-Deficient Mice on Atherosclerotic Background. Cells. 2021; 10(6):1292. https://doi.org/10.3390/cells10061292

Chicago/Turabian Style

Künstner, Axel, Redouane Aherrahrou, Misa Hirose, Petra Bruse, Saleh M. Ibrahim, Hauke Busch, Jeanette Erdmann, and Zouhair Aherrahrou. 2021. "Effect of Differences in the Microbiome of Cyp17a1-Deficient Mice on Atherosclerotic Background" Cells 10, no. 6: 1292. https://doi.org/10.3390/cells10061292

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