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

邻苯二甲酸单乙基己酯引发脂肪细胞炎症反应,特征为脂质和细胞因子通路的改变

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作者:Sara Manteiga, Kyongbum Lee

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

Conclusions

Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARγ.

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.

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