Please use this identifier to cite or link to this item:
Title: A novel mechanism of monoethylhexyl phthalate in lipid accumulation via inhibiting fatty acid beta-oxidation on hepatic cells
Authors: Xu, Tengfei
Lim, Yan Ting
Chen, Liyan
Zhao, Haoduo
Low, Jian Hui
Xia, Yun
Sobota, Radoslaw Mikolaj
Fang, Mingliang
Keywords: Engineering::Environmental engineering
Issue Date: 2020
Source: Xu, T., Lim, Y. T., Chen, L., Zhao, H., Low, J. H., Xia, Y., Sobota, R. M. & Fang, M. (2020). A novel mechanism of monoethylhexyl phthalate in lipid accumulation via inhibiting fatty acid beta-oxidation on hepatic cells. Environmental Science and Technology, 54(24), 15925-15934.
Project: M4011732.030
Journal: Environmental Science and Technology 
Abstract: Monoethylhexyl phthalate (MEHP) is one of the main active metabolites of the plasticizer di(2-ethylhexyl) phthalate. It has been known that MEHP has an impact on lipolysis; however, its mechanism on the cellular lipid metabolism remains largely unclear. Here, we first utilized global lipid profiling to fully characterize the lipid synthesis and degradation pathways upon MEHP treatment on hepatic cells. Meanwhile, we further identified the possible MEHP-targeted proteins in living cells using the cellular thermal shift assay (CETSA) method. The lipidomics results showed that there was a significant accumulation of fatty acids and other lipids in the cell. The CETSA identified 18 proteins and fatty acid β-oxidation inhibition pathways that were significantly perturbed. MEHP's binding with selected proteins HADH and HSD17B10 was further evaluated using molecule docking, and results showed that MEHP has higher affinities as compared to endogenous substrates, which was further experimentally confirmed in the surface plasma resonance interaction assay. In summary, we found a novel mechanism for MEHP-induced lipid accumulation, which was probably due to its inhibitive effects on the enzymes in fatty acid β-oxidation. This mechanism substantiates the public concerns on the high exposure level to plasticizers and their possible role as an obesogen.
ISSN: 0013-936X
DOI: 10.1021/acs.est.0c01073
Schools: School of Civil and Environmental Engineering 
Lee Kong Chian School of Medicine (LKCMedicine) 
Research Centres: Nanyang Environment and Water Research Institute 
Rights: © 2020 American Chemical Society. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:CEE Journal Articles
LKCMedicine Journal Articles
NEWRI Journal Articles

Citations 20

Updated on Oct 1, 2023

Web of ScienceTM
Citations 20

Updated on Sep 29, 2023

Page view(s)

Updated on Oct 3, 2023

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.