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Phthalate exposure increases fatty acid oxidation in cardiac muscle cells
Author(s) -
Posnack Nikki,
Idrees Rabia,
Swift Luther,
Lee Norman,
Sarvazyan Narine
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1036.14
Subject(s) - phthalate , downregulation and upregulation , peroxisome , beta oxidation , chemistry , peroxisome proliferator activated receptor , fatty acid , gene expression , microarray , endocrinology , biochemistry , microarray analysis techniques , medicine , receptor , biology , gene , organic chemistry
Di(2‐ethylhexyl)phthalate (DEHP) is a widely used plasticizer found in a variety of medical products. Confluent layers of neonatal rat cardiomyocytes were exposed to clinically relevant concentrations of DEHP for 72 hours. Affymetrix 1.0 ST arrays were utilized to assess changes in gene expression following DEHP exposure, and mRNA expression was validated by qRT‐PCR. Gene ontology (GO) analysis revealed significant over‐representation of GO categories associated with metabolic processes in DEHP‐treated samples. Specifically, DEHP exposure resulted in a significant upregulation in genes associated with fatty acid oxidation. To confirm microarray data, cardiomyocytes were cultured in glucose‐free culture media containing physiological concentrations of fatty acids. DEHP‐treated cardiomyocytes utilized a significantly higher amount of fatty acids compared with control samples. Moreover, immunocytochemistry revealed enhanced staining for mitochondria and PPARα in DEHP‐treated samples compared with control. Studies conducted using a PPARα agonist (Wy‐14643) suggested that the observed changes in utilization of metabolic substrates can be explained, at least in part, by upregulation of the PPARα nuclear receptor. Supported by the NIH (F32ES019057 to NGP).