Cell Biology and Toxicology

, Volume 33, Issue 6, pp 511–526 | Cite as

Comparative microarray analyses of mono(2-ethylhexyl)phthalate impacts on fat cell bioenergetics and adipokine network

  • Huai-Chih Chiang
  • Chih-Hong Wang
  • Szu-Ching Yeh
  • Yi-Hua Lin
  • Ya-Ting Kuo
  • Chih-Wei Liao
  • Feng-Yuan Tsai
  • Wei-Yu Lin
  • Wen-Han Chuang
  • Tsui-Chun Tsou
Original Article

Abstract

Cellular accumulation of mono(2-ethylhexyl)phthalate (MEHP) has been recently demonstrated to disturb fat cell energy metabolism; however, the underlying mechanism remained unclear. The study aimed to determine how MEHP influenced fat cell transcriptome and how the changes might contribute to bioenergetics. Because of the pivotal role of PPARγ in energy metabolism of fat cells, comparative microarray analysis of gene expression in 3T3-L1 adipocytes treated with both MEHP and rosiglitazone was performed. Pathway enrichment analysis and gene ontology (GO) enrichment analysis revealed that both treatments caused up-regulation of genes involved in PPAR signaling/energy metabolism-related pathways and down-regulation of genes related to adipokine/inflammation signals. MEHP/rosiglitazone-treated adipocytes exhibited increased levels of lipolysis, glucose uptake, and glycolysis; the gene expression profiles provided molecular basis for the functional changes. Moreover, MEHP was shown to induce nuclear translocation and activation of PPARγ. The similarity in gene expression and functional changes in response to MEHP and rosiglitazone suggested that MEHP influenced bioenergetics and adipokine network mainly via PPARγ. Importantly, adipokine levels in C57BL/6J mice with di(2-ethylhexyl)phthalate (DEHP) treatments provided in vivo evidence for microarray results. On the basis of correlation between gene expression and functional assays, possible involvements of genes in bioenergetics of MEHP-treated adipocytes were proposed.

Keywords

Phthalates Endocrine disruptor Energy metabolism PPARγ Adipocytes 

Abbreviations

βAR

β-Adrenergic receptor

DAVID

Database for Annotation, Visualization and Integrated Discovery

DEHP

di(2-Ethylhexyl)phthalate

FABPs

Fatty acid-binding proteins

GO

Gene ontology

HFD

High-fat diet

KEGG

Kyoto Encyclopedia of Genes and Genomes

MEHP

Mono(2-ethylhexyl)phthalate

Mlycd

Malonyl-CoA decarboxylase

NCD

Normal chow diet

NEFA

Non-esterified fatty acids

OCR

Oxygen consumption rate

PANTHER

Protein Analysis through Evolutionary Relationships

PCA

Principal component analysis

PDC

Pyruvate dehydrogenase complex

PDH

Pyruvate dehydrogenase

PPRE

PPAR response element

REVIGO

Reduce + Visual Gene Ontology

T2DM

Type 2 diabetes mellitus

WAT

White adipose tissue

Notes

Acknowledgments

This work was supported by grants from the Ministry of Science and Technology (101-2314-B-400-003-MY3, 102-2811-B-400-015, and 103-2811-B-400-022) and the National Health Research Institutes (EO-103-PP-03 and EO-104-PP-03) in Taiwan.

Supplementary material

10565_2016_9380_MOESM1_ESM.docx (84 kb)
ESM 1 (DOCX 84 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.National Institute of Environmental Health SciencesNational Health Research InstitutesZhunanTaiwan
  2. 2.Department of Biological Science and TechnologyNational Chiao Tung UniversityHsinchuTaiwan

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