Perfluorooctanoic acid affects in vitro adipogenesis in murine preadipocytes acting as an inducer of hypertrophic adipocytes

Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a key regulator of adipose tissue expansion, coordinating adipocyte physiological differentiation and maturation. In this study we evaluated the PPAR-γ effects of perfluorooctanoic acid (PFOA), a perfluorinated alkylated environmental obesogen, associated with an increased risk of diabetes, during adipogenic differentiation of 3T3-L1 murine cells. In particular, using in vitro monoculture (differentiating preadipocytes exposed to PFOA) or co-culture systems (differentiating preadipocytes in contact with PFOA-induced dysfunctional mature adipocytes) we examined adipocytes morphology and biological functions such as adipogenesis, insulin sensitivity and lipolytic response to adrenergic compounds. Exposure to PFOA (0.1-10 μM) promoted adipocyte hypertrophy inducing the formation of larger lipid vacuoles. These effects were also evident in the co-culture system, where paracrine factors released by PFOA-induced hypertrophic adipocytes influenced preadipocytes differentiation. Furthermore, both in the mono-culture and in the co-culture systems, PFOA exposure induced a metabolically unhealthy adipocyte phenotype affecting insulin sensitivity. Finally, findings obtained in mono-culture system evidence that these effects induced by PFOA may be related to its capability to affect lipid metabolism and pro/anti-inflammatory adipokine expression. This study, therefore, draws attention on PFOA as an obesogenic factor promoting adipocyte metabolic dysregulation and dysfunctional paracrine signaling.