Monoethylhexyl Phthalate Elicits an Inflammatory Response in Adipocytes Characterized by Alterations in Lipid and Cytokine Pathways.

FAT cells; LIPID metabolism; DNA analysis; FATTY acid analysis; ANALYTICAL biochemistry; ANIMAL experimentation; COLLECTION & preservation of biological specimens; CELL culture; CYTOKINES; GENE expression; INFLAMMATION; LIQUID chromatography; MASS spectrometry; MICE; POLLUTANTS; PROBABILITY theory; RESEARCH funding; T-test (Statistics); PROTEOMICS; CARBOCYCLIC acids; DATA analysis software; DESCRIPTIVE statistics; METABOLOMICS; PHYSIOLOGY

BACKGROUND: A growing body of evidence links endocrine-disrupting chemicals (EDCs) with obesity-related metabolic diseases. While it has been shown that EDCs can predispose individuals toward adiposity by affecting developmental processes, little is known about the chemicals' effects on adult adipose tissue. OBJECTIVES: Our aim was to study the effects of low, physiologically relevant doses of EDCs on differentiated murine adipocytes. METHODS: We combined metabolomics, proteomics, and gene expression analysis to characterize the effects of mono-ethylhexyl phthalate (MEHP) in differentiated adipocytes. RESULTS: Repeated exposure to MEHP over several days led to changes in metabolite and enzyme levels indicating elevated lipogenesis and lipid oxidation. The chemical exposure also increased expression of major inflammatory cytokines, including chemotactic factors. Proteomic and gene expression analysis revealed significant alterations in pathways regulated by peroxisome proliferator activated receptor-γ (PPARγ). Inhibiting the nuclear receptor's activity using a chemical antagonist abrogated not only the alterations in PPARγ-regulated metabolic pathways, but also the increases in cytokine expression. CONCLUSIONS: Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARγ. CITATION: Manteiga S, Lee K. 2017. Monoethylhexyl phthalate elicits an inflammatory response in adipocytes characterized by alterations in lipid and cytokine pathways. Environ Health Perspect 125:615-622; http://dx.doi.org/10.1289/EHP464 [ABSTRACT FROM AUTHOR]

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