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Table 5 Experimental binding/agonistic effects of PFAS to PPARγ, PPARβ/δ and PPARα (see also Involvement of PPARs section, Results)

From: Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

Compound and activity

Test system (organism)

Reference

PPARγ

 PFBS exposure – causes elevated expression of PPARγ (b)

In vitro (HepG2)

[224]

 PFOA – can activate PPARγ (e)

In vivo (mussel)

[225]

 PFOA – agonistic activity towards PPARγ (f)

In vitro (HEK 293)

[226]

 PFCAs – C8 to C14 showed an agonistic activity towards PPARγ, in HPA cells the activity increased from C8 to C11 and then fluctuated, in 3 T3-L1 the activity increased from C8 to C13 and then slightly fluctuated (g)

In vitro (HPA-s; HEK 293; 3 T3-L1)

[147]

 PFCAs – bind to PPARγ, binding affinity increased from C4 to C11 and then decreased slightly from C12 to C18 (c)

In vitro (HepG2)

[148]

 PFSAs – binding to PPARγ, binding affinity is stronger compared to PFCAs with the same carbon chain-length (c)

In vitro (HepG2)

[148]

 PFOA and PFOS – bind to PPARγ, PFOA shows a higher binding affinity compared to PFOS (d)

In vitro (buffer solution)

[227]

 PFOS binds to PPARγ – agonistic activity (a)

In vitro (3 T3-L1; HEK 293)

[122]

 6:2 Cl-PFAES binds to PPARγ - agonistic activity (a)

In vitro (3 T3-L1; HEK 293)

[122]

 8:2 Cl-PFAES binds to PPARγ - agonistic activity (a)

In vitro (3 T3-L1; HEK 293)

[122]

 HFPO-TA and HFPO-DA – agonistic activity towards PPARγ (f)

In vitro (HEK 293)

[226]

 PFAAs - containing carbon chain-length from C6 to C12 may alter the PPARγ activity; sulfonic acid groups showed a higher affinity to bind to PPARγ compared to carboxylic acids with the same carbon chain length (h)

In silico (Molecular dynamic calculations)

[228]

 DONA – shows the ability to activate PPARγ (h)

In silico (Molecular dynamic calculations)

[228]

PPARβ/δ

 PFBA, PFHxS and PFOS – binds to PPARβ/δ (d)

In vitro (buffer solution)

[227]

 PFOS binds to PPARβ/δ – agonistic activity (a)

In vitro (3 T3-L1; HEK 293)

[122]

 6:2 and 8:2 Cl-PFAES bind to PPARβ/δ - agonistic activity (a)

In vitro (3 T3-L1; HEK 293)

[122]

PPARα

 HFPO-DA – PPARα (i) activation

Maternal and foetal liver tissue (rat)

[229]

 PFBS – PPARα (b) activation

In vitro (HepG2)

[224]

 HFPO-DA – PPARα (j) activation

New-born pup liver tissue (rat)

[121]

 PFHxA and PFNA – strong binding to PPARα (d)

In vitro (buffer solution)

[227]

 PFOS – agonistic activity towards PPARα (a)

In vitro (3 T3-L1 cells)

[122],

 6:2 Cl-PFESA – strong binding to PPARα (k)

In vitro (3 T3-L1 cells)

[230]

 PFBA, PFHxA, PFOA, PFHxS and PFOS – PPARα (l) activation

In vitro (HepG2)

[231]

 PFOA – PPARα (m) activation

In vitro (MCF-10A)

[232]

  1. Abbreviations: 3 T3-L1 Mouse preadipocyte cells, Cl-PFAES Chlorinated polyfluorinated ether sulfonates, DONA 4,8-dioxa-3H-perfluorononanoic acid, HEK 293 Human embryonal kidney cells, HepG2 Human hepatoma cell line, HFPO-DA Hexafluoropropylene oxide-dimer acid, HFPO-TA Hexafluoropropylene oxide trimer acid, HPA-s Human preadipocytes-subcutaneous, MCF-10A Human mammary epithelial cells, PPAR Peroxisome proliferator-activated receptor, PFAA Perfluoroalkyl acids, PFBA Perfluorobutanoic acid, PFBS Perfluorobutane sulfonate, PFCA Perfluorocarboxylic acid, PFHxA Perfluorohexanoic acid, PFHxS Perfluorohexane sulfonate, PFNA Perfluorononanoic acid, PFOA Perfluorooctanoic acid, PFOS Perfluorooctane sulfonate, PFSAs Perfluorosulfonic acids