Environmental Chemicals Modulate Polar Bear (Ursus maritimus) Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and Adipogenesis in Vitro.
We studied interactions between polar bear peroxisome proliferator-activated receptor gamma (pbPPARG) and selected compounds using a luciferase reporter assay and predictions through molecular docking. Furthermore, we studied adipogenesis by liver and adipose tissue extracts from a polar bear and three synthetic mixtures of contaminants in murine 3T3-L1 preadipocytes and polar bear adipose tissue-derived stem cells (pbASCs). PCB153 and p,p'-DDE antagonized pbPPARG, although their predicted receptor-ligand affinity was weak. PBDEs, tetrabromobisphenol A, and PCB170 had a weak agonistic effect on pbPPARG, while hexabromocyclododecane, bisphenol A, oxychlordane, and endosulfan were weak antagonists. pbPPARG-mediated luciferase activity was suppressed by synthetic contaminant mixtures reflecting levels measured in polar bear adipose tissue, as were transcript levels of PPARG and the PPARG target gene fatty acid binding protein 4 (FABP4) in pbASCs. Contaminant extracts from polar bear tissues enhanced triglyceride accumulation in murine 3T3-L1 cells and pbASCs, whereas triglyceride accumulation was not affected by the synthetic mixtures. Chemical characterization of extracts using nontarget methods revealed presence of exogenous compounds that have previously been reported to induce adipogenesis. These compounds included phthalates, tonalide, and nonylphenol. In conclusion, major legacy contaminants in polar bear adipose tissue exert antagonistic effects on PPARG, but adipogenesis by a mixture containing emerging compounds may be enhanced through PPARG or other pathways.
Norwegian Polar Institute , Fram Centre, 9296 Tromsø, Norway.
Heli
H
Routti
Department of Biology, University of Bergen , 5020 Bergen, Norway.
Roger
R
Lille-Langøy
Norwegian Polar Institute , Fram Centre, 9296 Tromsø, Norway.|Department of Biology, University of Bergen , 5020 Bergen, Norway.
Mari K
MK
Berg
Department of Health Science and Technology, Aalborg University , 9220 Aalborg, Denmark.
Trine
T
Fink
Norwegian Institute for Air Research, Fram Centre , 9296 Tromsø, Norway.
Mikael
M
Harju
Department of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway , 9037 Tromsø, Norway.
Kurt
K
Kristiansen
Norwegian Institute for Air Research , 2007 Kjeller, Norway.
Pawel
P
Rostkowski
Department of Biology, University of Bergen , 5020 Bergen, Norway.
Marte
M
Rusten
Department of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway , 9037 Tromsø, Norway.
Ingebrigt
I
Sylte
Norwegian Polar Institute , Fram Centre, 9296 Tromsø, Norway.|Department of Biology, University of Bergen , 5020 Bergen, Norway.
Lene
L
Øygarden
Department of Biology, University of Bergen , 5020 Bergen, Norway.
Anders
A
Goksøyr
D017667:Adipocytes / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D051379:Mice; D062105:Molecular Docking Simulation; D047495:PPAR gamma / Q000378:metabolism*; D001503:Ursidae / Q000378:metabolism
D047495:PPAR gamma