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Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice
Exposure to ambient air particulate matter (PM(2.5)) is well established as a risk factor for cardiovascular and pulmonary disease. Both epidemiologic and controlled exposure studies in humans and animals have demonstrated an association between air pollution exposure and metabolic disorders such as...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874681/ https://www.ncbi.nlm.nih.gov/pubmed/31757983 http://dx.doi.org/10.1038/s41598-019-53716-y |
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author | Reyes-Caballero, Hermes Rao, Xiaoquan Sun, Qiushi Warmoes, Marc O. Penghui, Lin Sussan, Tom E. Park, Bongsoo Fan, Teresa W.-M. Maiseyeu, Andrei Rajagopalan, Sanjay Girnun, Geoffrey D. Biswal, Shyam |
author_facet | Reyes-Caballero, Hermes Rao, Xiaoquan Sun, Qiushi Warmoes, Marc O. Penghui, Lin Sussan, Tom E. Park, Bongsoo Fan, Teresa W.-M. Maiseyeu, Andrei Rajagopalan, Sanjay Girnun, Geoffrey D. Biswal, Shyam |
author_sort | Reyes-Caballero, Hermes |
collection | PubMed |
description | Exposure to ambient air particulate matter (PM(2.5)) is well established as a risk factor for cardiovascular and pulmonary disease. Both epidemiologic and controlled exposure studies in humans and animals have demonstrated an association between air pollution exposure and metabolic disorders such as diabetes. Given the central role of the liver in peripheral glucose homeostasis, we exposed mice to filtered air or PM(2.5) for 16 weeks and examined its effect on hepatic metabolic pathways using stable isotope resolved metabolomics (SIRM) following a bolus of (13)C(6)-glucose. Livers were analyzed for the incorporation of (13)C into different metabolic pools by IC-FTMS or GC-MS. The relative abundance of (13)C-glycolytic intermediates was reduced, suggesting attenuated glycolysis, a feature found in diabetes. Decreased (13)C-Krebs cycle intermediates suggested that PM(2.5) exposure led to a reduction in the Krebs cycle capacity. In contrast to decreased glycolysis, we observed an increase in the oxidative branch of the pentose phosphate pathway and (13)C incorporations suggestive of enhanced capacity for the de novo synthesis of fatty acids. To our knowledge, this is one of the first studies to examine (13)C(6)-glucose utilization in the liver following PM(2.5) exposure, prior to the onset of insulin resistance (IR). |
format | Online Article Text |
id | pubmed-6874681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68746812019-12-04 Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice Reyes-Caballero, Hermes Rao, Xiaoquan Sun, Qiushi Warmoes, Marc O. Penghui, Lin Sussan, Tom E. Park, Bongsoo Fan, Teresa W.-M. Maiseyeu, Andrei Rajagopalan, Sanjay Girnun, Geoffrey D. Biswal, Shyam Sci Rep Article Exposure to ambient air particulate matter (PM(2.5)) is well established as a risk factor for cardiovascular and pulmonary disease. Both epidemiologic and controlled exposure studies in humans and animals have demonstrated an association between air pollution exposure and metabolic disorders such as diabetes. Given the central role of the liver in peripheral glucose homeostasis, we exposed mice to filtered air or PM(2.5) for 16 weeks and examined its effect on hepatic metabolic pathways using stable isotope resolved metabolomics (SIRM) following a bolus of (13)C(6)-glucose. Livers were analyzed for the incorporation of (13)C into different metabolic pools by IC-FTMS or GC-MS. The relative abundance of (13)C-glycolytic intermediates was reduced, suggesting attenuated glycolysis, a feature found in diabetes. Decreased (13)C-Krebs cycle intermediates suggested that PM(2.5) exposure led to a reduction in the Krebs cycle capacity. In contrast to decreased glycolysis, we observed an increase in the oxidative branch of the pentose phosphate pathway and (13)C incorporations suggestive of enhanced capacity for the de novo synthesis of fatty acids. To our knowledge, this is one of the first studies to examine (13)C(6)-glucose utilization in the liver following PM(2.5) exposure, prior to the onset of insulin resistance (IR). Nature Publishing Group UK 2019-11-22 /pmc/articles/PMC6874681/ /pubmed/31757983 http://dx.doi.org/10.1038/s41598-019-53716-y Text en © The Author(s) 2019 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 Reyes-Caballero, Hermes Rao, Xiaoquan Sun, Qiushi Warmoes, Marc O. Penghui, Lin Sussan, Tom E. Park, Bongsoo Fan, Teresa W.-M. Maiseyeu, Andrei Rajagopalan, Sanjay Girnun, Geoffrey D. Biswal, Shyam Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice |
title | Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice |
title_full | Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice |
title_fullStr | Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice |
title_full_unstemmed | Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice |
title_short | Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice |
title_sort | air pollution-derived particulate matter dysregulates hepatic krebs cycle, glucose and lipid metabolism in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874681/ https://www.ncbi.nlm.nih.gov/pubmed/31757983 http://dx.doi.org/10.1038/s41598-019-53716-y |
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