4.7 Article

Phthalate exposure causes browning-like effects on adipocytes in vitro and in vivo

期刊

FOOD AND CHEMICAL TOXICOLOGY
卷 142, 期 -, 页码 -

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2020.111487

关键词

Plasticizer; Fat cells; Mitochondria; Peroxisomes; Fatty acid oxidation; Energy metabolism

资金

  1. Ministry of Science and Technology [105-2320-B-400-022, 106-2320-B-400-006, 1072320-B-400-001]
  2. National Health Research Institutes [EM-105-PP-03, EM-106-PP-03, EM-107-PP-03]

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Mono(2-ethylhexyl)phthalate (MEHP) promotes adipogenesis via PPAR gamma. PPAR gamma 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 beta-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. PPARy 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, Adrbl, Adrb3, Ppargcla, and Ucpl) in WAT, increased blood FGF21 levels, and higher amounts of BAT, supporting the browning-like effects in vivo.

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