title: Effect of exposure to atmospheric ultrafine particles on production of free fatty acids and lipid metabolites in the mouse small intestine.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We sought to assess whether exposure to ambient UFP (diameter < 180 nm) increased free fatty acids and lipid metabolites in the mouse small intestine.
  
  
  METHODS
  Ldlr-null mice were exposed to filtered air (FA) or UFP collected at an urban Los Angeles, California, site that was heavily affected by vehicular emissions; the exposure was carried out for 10 weeks in the presence or absence of D-4F, an apolipoprotein A-I mimetic peptide with antioxidant and anti-inflammation properties on a high-fat or normal chow diet.
  
  
  RESULTS
  Compared with 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 (AA) 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. Although 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.
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Rongsong
authors.initials: R
authors.lastname: Li
authors.forename: Kaveh
authors.initials: K
authors.lastname: Navab
authors.forename: Greg
authors.initials: G
authors.lastname: Hough
authors.forename: Nancy
authors.initials: N
authors.lastname: Daher
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Mittelstein
authors.forename: Katherine
authors.initials: K
authors.lastname: Lee
authors.forename: Payam
authors.initials: P
authors.lastname: Pakbin
authors.forename: Arian
authors.initials: A
authors.lastname: Saffari
authors.forename: May
authors.initials: M
authors.lastname: Bhetraratana
authors.forename: Dawoud
authors.initials: D
authors.lastname: Sulaiman
authors.forename: Tyler
authors.initials: T
authors.lastname: Beebe
authors.forename: Lan
authors.initials: L
authors.lastname: Wu
authors.forename: Nelson
authors.initials: N
authors.lastname: Jen
authors.forename: Eytan
authors.initials: E
authors.lastname: Wine
authors.forename: Chi-Hong
authors.initials: CH
authors.lastname: Tseng
authors.forename: Jesus A
authors.initials: JA
authors.lastname: Araujo
authors.forename: Alan
authors.initials: A
authors.lastname: Fogelman
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.forename: Mohamed
authors.initials: M
authors.lastname: Navab
authors.forename: Tzung K
authors.initials: TK
authors.lastname: Hsiai
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000706:statistics & numerical data; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001272:Atmosphere / Q000737:chemistry; D004041:Dietary Fats / Q000378:metabolism; D005228:Fatty Acids, Essential / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D015141:Los Angeles; D051379:Mice; D018345:Mice, Knockout; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D001335:Vehicle Emissions
chemical_list: D000393:Air Pollutants; D016632:Apolipoprotein A-I; C465468:D-4F peptide; D004041:Dietary Fats; D005228:Fatty Acids, Essential; D052638:Particulate Matter; D001335:Vehicle Emissions