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Targeted Metabolomics Reveals Abnormal Hepatic Energy Metabolism by Depletion of β-Carotene Oxygenase 2 in Mice
β-carotene oxygenase 2 (BCO2) is a carotenoid cleavage enzyme located in the inner mitochondrial membrane. Ablation of BCO2 impairs mitochondrial function leading to oxidative stress. Herein, we performed a targeted metabolomics study using ultrahigh performance liquid chromatography-tandem mass spe...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677115/ https://www.ncbi.nlm.nih.gov/pubmed/29116185 http://dx.doi.org/10.1038/s41598-017-15222-x |
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author | Wu, Lei Guo, Xin Lyu, Yi Clarke, Stephen L. Lucas, Edralin A. Smith, Brenda J. Hildebrand, Deana Wang, Weiqun Medeiros, Denis M. Shen, Xinchun Lin, Dingbo |
author_facet | Wu, Lei Guo, Xin Lyu, Yi Clarke, Stephen L. Lucas, Edralin A. Smith, Brenda J. Hildebrand, Deana Wang, Weiqun Medeiros, Denis M. Shen, Xinchun Lin, Dingbo |
author_sort | Wu, Lei |
collection | PubMed |
description | β-carotene oxygenase 2 (BCO2) is a carotenoid cleavage enzyme located in the inner mitochondrial membrane. Ablation of BCO2 impairs mitochondrial function leading to oxidative stress. Herein, we performed a targeted metabolomics study using ultrahigh performance liquid chromatography-tandem mass spectroscopy and gas chromatography-mass spectroscopy to discriminate global metabolites profiles in liver samples from six-week-old male BCO2 systemic knockout (KO), heterozygous (Het), and wild type (WT) mice fed a chow diet. Principal components analysis revealed distinct differences in metabolites in the livers of KO mice, compared to WT and Het mice. However, no marked difference was found in the metabolites of the Het mouse liver compared to the WT. We then conducted random forest analysis to classify the potential biomarkers to further elucidate the different metabolomics profiles. We found that systemic ablation of BCO2 led to perturbations in mitochondrial function and metabolism in the TCA cycle, amino acids, carnitine, lipids, and bile acids. In conclusion, BCO2 is essential to macronutrient and mitochondrial metabolism in the livers of mice. The ablation of BCO2 causes dysfunctional mitochondria and altered energy metabolism, which further leads to systemic oxidative stress and inflammation. A single functional copy of BCO2 largely rescues the hepatic metabolic homeostasis in mice. |
format | Online Article Text |
id | pubmed-5677115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56771152017-11-15 Targeted Metabolomics Reveals Abnormal Hepatic Energy Metabolism by Depletion of β-Carotene Oxygenase 2 in Mice Wu, Lei Guo, Xin Lyu, Yi Clarke, Stephen L. Lucas, Edralin A. Smith, Brenda J. Hildebrand, Deana Wang, Weiqun Medeiros, Denis M. Shen, Xinchun Lin, Dingbo Sci Rep Article β-carotene oxygenase 2 (BCO2) is a carotenoid cleavage enzyme located in the inner mitochondrial membrane. Ablation of BCO2 impairs mitochondrial function leading to oxidative stress. Herein, we performed a targeted metabolomics study using ultrahigh performance liquid chromatography-tandem mass spectroscopy and gas chromatography-mass spectroscopy to discriminate global metabolites profiles in liver samples from six-week-old male BCO2 systemic knockout (KO), heterozygous (Het), and wild type (WT) mice fed a chow diet. Principal components analysis revealed distinct differences in metabolites in the livers of KO mice, compared to WT and Het mice. However, no marked difference was found in the metabolites of the Het mouse liver compared to the WT. We then conducted random forest analysis to classify the potential biomarkers to further elucidate the different metabolomics profiles. We found that systemic ablation of BCO2 led to perturbations in mitochondrial function and metabolism in the TCA cycle, amino acids, carnitine, lipids, and bile acids. In conclusion, BCO2 is essential to macronutrient and mitochondrial metabolism in the livers of mice. The ablation of BCO2 causes dysfunctional mitochondria and altered energy metabolism, which further leads to systemic oxidative stress and inflammation. A single functional copy of BCO2 largely rescues the hepatic metabolic homeostasis in mice. Nature Publishing Group UK 2017-11-07 /pmc/articles/PMC5677115/ /pubmed/29116185 http://dx.doi.org/10.1038/s41598-017-15222-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wu, Lei Guo, Xin Lyu, Yi Clarke, Stephen L. Lucas, Edralin A. Smith, Brenda J. Hildebrand, Deana Wang, Weiqun Medeiros, Denis M. Shen, Xinchun Lin, Dingbo Targeted Metabolomics Reveals Abnormal Hepatic Energy Metabolism by Depletion of β-Carotene Oxygenase 2 in Mice |
title | Targeted Metabolomics Reveals Abnormal Hepatic Energy Metabolism by Depletion of β-Carotene Oxygenase 2 in Mice |
title_full | Targeted Metabolomics Reveals Abnormal Hepatic Energy Metabolism by Depletion of β-Carotene Oxygenase 2 in Mice |
title_fullStr | Targeted Metabolomics Reveals Abnormal Hepatic Energy Metabolism by Depletion of β-Carotene Oxygenase 2 in Mice |
title_full_unstemmed | Targeted Metabolomics Reveals Abnormal Hepatic Energy Metabolism by Depletion of β-Carotene Oxygenase 2 in Mice |
title_short | Targeted Metabolomics Reveals Abnormal Hepatic Energy Metabolism by Depletion of β-Carotene Oxygenase 2 in Mice |
title_sort | targeted metabolomics reveals abnormal hepatic energy metabolism by depletion of β-carotene oxygenase 2 in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677115/ https://www.ncbi.nlm.nih.gov/pubmed/29116185 http://dx.doi.org/10.1038/s41598-017-15222-x |
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