Triphenyl phosphate enhances adipogenic differentiation, glucose uptake and lipolysis via endocrine and noradrenergic mechanisms.
The use of triphenyl phosphate (TPhP) as a flame retardant or plasticizer has increased during the last decade, resulting in widespread human exposure without commensurate toxicity assessment. The main objectives of this study were to assess the in vitro effect of TPhP and its metabolite diphenyl phosphate (DPhP) on the adipogenic differentiation of 3T3-L1 cells, as well as glucose uptake and lipolysis in differentiated 3T3-L1 adipocytes. TPhP increased pre-adipocyte proliferation and subsequent adipogenic differentiation of 3T3-L1 cells, coinciding with increased transcription in the CEBP and PPARG pathway. Treatment of mature adipocytes with TPhP increased the basal- and insulin stimulated- uptake of the glucose analog 2-[N (-7-nitrobenz-2-oxa1, 3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG). This effect was ablated by inhibition of PI3K, a member of the insulin signaling pathway. DPhP had no significant effect on cell proliferation and, compared to TPhP, a weaker effect on adipogenic differentiation and on 2-NBDG uptake. Both TPhP and DPhT significantly enhanced the isoproterenol-induced lipolysis, most likely by increasing the expression of lipolytic genes during and after differentiation. This study suggests that TPhP increases adipogenic differentiation, glucose uptake, and lipolysis in 3T3-L1 cells through endocrine and noradrenergic mechanisms.
Department of Environmental Toxicology, University of California at Davis, Davis, CA, USA.
German
G
Cano-Sancho
Department of Environmental Toxicology, University of California at Davis, Davis, CA, USA.
Anna
A
Smith
Department of Environmental Toxicology, University of California at Davis, Davis, CA, USA. Electronic address: mlamerrill@ucdavis.edu.
Michele A
MA
La Merrill
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005411:Flame Retardants / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D010755:Organophosphates / Q000494:pharmacology*; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D005411:Flame Retardants; D051275:Glucose Transporter Type 4; D010755:Organophosphates; D047495:PPAR gamma; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D005947:Glucose; C005445:triphenyl phosphate
Diabetes mellitus; Diphenyl phosphate; Fatty acids; Firemaster 550; Obesity; Triphenyl phosphate