title: Comparative microarray analyses of mono(2-ethylhexyl)phthalate impacts on fat cell bioenergetics and adipokine network.
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.
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 350, Taiwan.
authors.forename: Huai-Chih
authors.initials: HC
authors.lastname: Chiang
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 300, Taiwan.
authors.forename: Chih-Hong
authors.initials: CH
authors.lastname: Wang
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 350, Taiwan.
authors.forename: Szu-Ching
authors.initials: SC
authors.lastname: Yeh
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 350, Taiwan.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Lin
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 350, Taiwan.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Kuo
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 350, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Liao
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 350, Taiwan.
authors.forename: Feng-Yuan
authors.initials: FY
authors.lastname: Tsai
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 300, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 300, Taiwan.
authors.forename: Wen-Han
authors.initials: WH
authors.lastname: Chuang
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 350, Taiwan. tctsou@nhri.org.tw.
authors.forename: Tsui-Chun
authors.identifier: 0000-0003-3546-9901
authors.initials: TC
authors.lastname: Tsou
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D054392:Adipokines; D005227:Fatty Acids; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate; D005947:Glucose
keywords: Adipocytes; Endocrine disruptor; Energy metabolism; PPARγ; Phthalates