Benzophenone-3 and benzophenone-8 exhibit obesogenic activity via peroxisome proliferator-activated receptor gamma pathway

Abstract

Benzophenone-3 (BP-3) and benzopenone-8 (BP-8) are commonly used ultraviolet (UV) filter ingredients in diverse sunscreen products. Recently, the obesogenic activity of avobenzone, a long wave UV A filter, was elucidated in the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs). In this study, the obesogenic potentials of BP-3 and BP-8 were investigated because of their chemical similarity to avobenzone. During the adipogenesis in hBM-MSCs, BP-3 and BP-8 (EC50, 25.05 and 43.20 mu M, respectively) potently promoted adiponectin secretion than avobenzone (EC50, 72.69 mu M). In target identification, both BP-3 and BP-8 directly bound to peroxisome proliferator-activated receptor gamma (PPAR gamma), which was associated with the recruitment of steroid receptor coactivator-2 (SRC-2). BP-3 functioned as a PPAR gamma full agonist whereas BP-8 was a PPAR gamma partial agonist. In addition, BP-3 and BP-8 significantly increased the gene transcription of PPAR alpha, PPAR gamma, and major lipid metabolism-associated enzymes in human epidermal keratinocytes, a major target site of UV filters in human skin. This study suggests that BP-3 and BP-8 are obesogenic environmental chemicals similar to phthalates, bisphenols, and organotins.