國家衛生研究院 NHRI:Item 3990099045/12774

NHRI > National Institute of Environmental Health Sciences > Tsui-Chun Tsou > Periodical Articles > Item 3990099045/12774

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12774

Title:	Phthalate exposure causes browning-like effects on adipocytes in vitro and in vivo
Authors:	Hsu, JW;Nien, CY;Yeh, SC;Tsai, FY;Chen, HW;Lee, TS;Chen, SL;Kao, YH;Tsou, TC
Contributors:	National Institute of Environmental Health Sciences
Abstract:	Mono(2-ethylhexyl)phthalate (MEHP) promotes adipogenesis via PPARγ. PPARγ agonists, e.g., rosiglitazone (RSG), enhance adipocyte browning. However, scientific evidence regarding MEHP as a browning chemical is lacking. This study combined 3T3-L1 adipocytes and C57BL/6J mice to examine the potential roles of MEHP in browning. MEHP and the browning agent RSG caused similar energy metabolism in adipocytes. Both MEHP and RSG caused transcriptional changes involved in browning-associated thermogenesis, energy homeostasis, inflammatory response, and glucose uptake. MEHP-treated adipocytes exhibited brown adipocyte-like characteristics, i.e., increased mitochondrial proton leak, triiodothyronine-induced Bmp8b expression, decreased inflammation, and smaller lipid droplets. Increased PDK4 and PEPCK1 in MEHP/RSG-treated adipocytes could block glucose utilization for mitochondrial respiration. Mitochondrial/peroxisomal biogenesis and fatty acid β-oxidation in MEHP-treated adipocytes were enhanced. Candidate genes in promoting browning of MEHP-treated adipocytes were highlighted. In di(2-ethylhexyl)phthalate (DEHP)-treated mice, transcriptional changes in white adipose tissue (WAT) were associated with adipocyte differentiation, lipid synthesis, carbohydrate uptake, and WAT/brown adipose tissue (BAT) quantity. PPARγ and NR4A1 were predicted as the top two upstream regulators in orchestrating transcriptional changes. DEHP-treated mice exhibited actively expressed browning marker genes (i.e., Pparg, Adrb1, Adrb3, Ppargc1a, and Ucp1) in WAT, increased blood FGF21 levels, and higher amounts of BAT, supporting the browning-like effects in vivo.
Date:	2020-08
Relation:	Food and Chemical Toxicology. 2020 Aug;142:Article number 111487.
Link to:	http://dx.doi.org/10.1016/j.fct.2020.111487
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0278-6915&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000550060200024
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85086406714
Appears in Collections:	[Tsui-Chun Tsou] Periodical Articles

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