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Research Article Advance Publication

Environ Health Perspect; DOI:10.1289/ehp.1307036

Effect of Exposure to Atmospheric Ultrafine Particles on Production of Free Fatty Acids and Lipid Metabolites in the Mouse Small Intestine

Rongsong Li,1,2 Kaveh Navab,1 Greg Hough,1 Nancy Daher,3 Min Zhang,1 David Mittelstein,2 Katherine Lee,2 Payam Pakbin,3 Arian Saffari,2 May Bhetraratana,1 Dawoud Sulaiman,1 Tyler Beebe,1,2 Lan Wu,1,2 Nelson Jen,1,4 Eytan Wine,5 Chi-Hong Tseng,1 Jesus A. Araujo,1 Alan Fogelman,1 Constantinos Sioutas,3 Mohamed Navab,1 and Tzung K. Hsiai1,2,4 
Author Affiliations close
1Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, California, USA; 2Biomedical Engineering, University of Southern California, Los Angeles, California, USA; 3Civil and Environmental Engineering, University of Southern California, Los Angeles, California, USA; 4Department of Bioengineering, School of Engineering and Applied Science, University of California, Los Angeles, California, USA; 5Division of Pediatric Gastroenterology, Departments of Pediatrics and Physiology, University of Alberta, Edmonton, Alberta, Canada
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This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.

Citation: Li R, Navab K, Hough G, Daher N, Zhang M, Mittelstein D, Lee K, Pakbin P, Saffari A, Bhetraratana M, Sulaiman D, Beebe T, Wu L, Jen N, Wine E, Tseng CH, Araujo JA, Fogelman A, Sioutas C, Navab M, Hsiai TK. Effect of Exposure to Atmospheric Ultrafine Particles on Production of Free Fatty Acids and Lipid Metabolites in the Mouse Small Intestine. Environ Health Perspect;

Received: 2 May 2013
Accepted: 27 August 2014
Advance Publication: 29 August 2014

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Background and Objective: Exposure to ambient ultrafine particulate matter (UFP) is a well-recognized risk factor for cardiovascular and respiratory diseases. However, little is known about the effects of air pollution on gastrointestinal disorders. We sought to assess whether exposure to ambient ultrafine particles (UFP: diameter < 180 nm) increased free fatty acids and lipid metabolites in the mouse small intestine.

Methods and Results: LDLR-null mice were exposed to filtered air (FA) or UFP collected at an urban Los Angeles site heavily impacted by vehicular emissions for 10 weeks in the presence or absence of D-4F, an apolipoprotein A-I mimetic peptide with anti-oxidant and anti-inflammation properties on a high-fat or normal chow diet. Compared to FA, exposure to UFP significantly increased intestinal hydroxyeicosatetraenoic acids (HETEs), including 15-HETE, 12-HETE, 5-HETE, as well as hydroxyoctadecadienoic acids (HODEs), including 13-HODE and 9-HODE. Arachidonic acid and prostaglandin D2 (PGD2) as well as some of the lysophosphatidic acids (LPA) in the small intestine were also increased in response to UFP exposure. Administration of D-4F significantly reduced UFP-mediated increase in HETES, HODEs, AA, PGD2 and LPA. While exposure to UFP further led to shortened villus length accompanied by prominent macrophage and neutrophil infiltration into the intestinal villi, administration of D-4F mitigated macrophage infiltration.

Conclusions: Exposure to UFP promotes lipid metabolism, villus shortening and inflammatory responses in mouse small intestine, whereas administration of D-4F attenuated these effects. Our findings provide a basis to further assess the mechanisms underlying UFP-mediated lipid metabolism in the digestive system with clinical relevance to gut homeostasis and diseases.

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