Abstract 20762: Diesel Exhaust Induces Hyperlipidemia in Association With Downregulation of PPAR Alpha and Changes in Gut Microbiota
Introduction: Air pollution is associated with increased cardiovascular morbidity and mortality. Inhalation of ambient particulate matter has been shown to induce functional changes in plasma lipoproteins and atherosclerosis on a short- and long-term, respectively.
Hypothesis: Long-term exposures to ambient particulate may lead to dysregulation of lipid metabolism and dyslipidemia.
Methods: Male ApoE KO mice were exposed to inhaled Diesel Exhaust (DE) or filtered air (FA) for 6 hours/day, 5 days/week for 16 weeks. Plasma lipids and lipoproteins were evaluated by colorimetric methods and FPLC. Liver steatosis and composition of gut microbiota were evaluated by histology and sequencing. HepG2 cells were treated with Diesel Exhaust Particles (DEP) to dissect potential pathways involved in lipid dysregulation.
Results: DE-exposed animals exhibited increased plasma levels of cholesterol and triglycerides as well as increased triglyceride content in the liver as compared with FA controls. DE led to decreased mRNA and protein levels of PPARα, together with decreased mRNA levels of Acad9, which suggested decreased beta oxidation of fatty acids and decreased lipid catabolism. Pre-treatment of HepG2 cells with a methanol extract of DEP led to decreased levels of PPARα, Acad9 and content of triglycerides. Administration of PPARα agonist WY-14643 abolished those effects. DE also resulted in marked alteration of the gut microbiota as evidenced by the identification of 32 microbial taxa that were characteristic of the exposure conditions, and significant associations between the abundance of 24 taxa with liver triglycerides, 18 of which associated with PPARα protein levels as well, suggesting a pathogenic link.
Conclusions: Diesel exhaust led to dyslipidemia and liver steatosis in ApoE KO mice, likely due to down-regulation of PPAR alpha in the liver, in association with changes in gut microbiota.
Author Disclosures: F. Yin: None. W.S. Driscoll: None. D. Sulaiman: None. G. Ramanathan: None. J.A. Stewart: None. M. Mehrabian: None. S. Beaven: None. A.J. Lusis: None. M.E. Rosenfeld: None. J.A. Araujo: Research Grant; Significant; R56 ES016959-06.
- © 2016 by American Heart Association, Inc.