Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice

Hermes Reyes-Caballero, Xiaoquan Rao, Qiushi Sun, Marc O. Warmoes, Lin Penghui, Tom E. Sussan, Bongsoo Park, Teresa W.M. Fan, Andrei Maiseyeu, Sanjay Rajagopalan, Geoffrey D. Girnun, Shyam Biswal

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Abstract

Exposure to ambient air particulate matter (PM2.5) 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 PM2.5 for 16 weeks and examined its effect on hepatic metabolic pathways using stable isotope resolved metabolomics (SIRM) following a bolus of 13C6-glucose. Livers were analyzed for the incorporation of 13C into different metabolic pools by IC-FTMS or GC-MS. The relative abundance of 13C-glycolytic intermediates was reduced, suggesting attenuated glycolysis, a feature found in diabetes. Decreased 13C-Krebs cycle intermediates suggested that PM2.5 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 13C 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 13C6-glucose utilization in the liver following PM2.5 exposure, prior to the onset of insulin resistance (IR).

Original languageEnglish (US)
Article number17423
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Citric Acid Cycle
Particulate Matter
Air Pollution
Lipid Metabolism
Glucose
Liver
Glycolysis
Air
Pentose Phosphate Pathway
Metabolomics
Metabolic Networks and Pathways
Isotopes
Lung Diseases
Insulin Resistance
Homeostasis
Cardiovascular Diseases
Fatty Acids

ASJC Scopus subject areas

  • General

Cite this

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.

In: Scientific Reports, Vol. 9, No. 1, 17423, 01.12.2019.

Research output: Contribution to journalArticle

Reyes-Caballero, H, Rao, X, Sun, Q, Warmoes, MO, Penghui, L, Sussan, TE, Park, B, Fan, TWM, Maiseyeu, A, Rajagopalan, S, Girnun, GD & Biswal, S 2019, 'Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice', Scientific Reports, vol. 9, no. 1, 17423. https://doi.org/10.1038/s41598-019-53716-y
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. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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