Sunscreen filter octocrylene is a potential obesogen by acting as a PPARγ partial agonist. (1st February 2022)

• Record Type: Journal Article
• Authors: Ko, Hyejin; An, Seungchan; Ahn, Sungjin; Park, In Guk; Gong, Junpyo; Hwang, Seok Young; Oh, Soyeon; Ki, Min Won; Jin, Sun Hee; Choi, Won Jun; Noh, Minsoo
• Is Part Of: Toxicology letters. Volume 355(2022)
• Page Start: 141
• Page End: 149
• Publication Date: 2022-02-01
• Subjects: ACAT2 acetyl-CoA acetyltransferase 2 -- AR androgen receptor -- BBP benzyl butyl phthalate -- BP-3 benzophenone-3 -- BP-8 benzophenone-8 -- DBP dibutyl phthalate -- DEHP bis(2-ethylhexyl) phthalate -- DMEM Dulbecco Modified Eagle's Medium -- ELISA enzyme-linked immunosorbent assay -- ER estrogen receptor -- FABP4 fatty acid-binding protein 4 -- FBS fetal bovine serum -- hBM-MSCs human bone marrow mesenchymal stem cells -- HMGCR 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase -- HMGCS1 3-hydroxy-3-methylglutaryl-CoA synthase 1 -- IBMX 3-isobutyl-1-methylxanthine -- LBD ligand binding domain -- MEHP mono(2-ethylhexyl) phthalate -- NHKs normal human keratinocytes -- OC octocrylene -- PBS phosphate-buffered saline -- PDB Protein Data Bank -- PGC-1α peroxisome proliferator-activated receptor gamma coactivator 1-alpha -- PPAR peroxisome proliferator-activated receptor -- PRIP/RAP250 peroxisome proliferator-activated receptor gamma-interacting protein /nuclear receptor-activating protein 250 -- qHTS quantitative high-throughput screening -- Q-RT-PCR quantitative real-time reverse transcription-polymerase chain reaction -- RIP140 receptor-interacting protein 140 -- RXR retinoid X receptor -- SRC nuclear receptor coactivator -- TBT tributyltin -- Tox21 toxicology in the 21st century -- TRAP220/DRIP-2 thyroid hormone receptor-associated protein complex 220/vitamin D receptor-interacting protein-2 -- TR-FRET time-resolved fluorescence resonance energy transfer; Octocrylene -- Peroxisome proliferator-activated receptor gamma -- Human bone marrow mesenchymal stem cells -- Obesogen -- UV B filter; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2021.12.001
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: Ultraviolet B filter octocrylene (OC) promoted adipogenesis in hBM-MSCs. OC directly bound to PPARγ and recruited coactivator proteins, SRC-1 and SRC-2. OC acts as a PPARγ partial agonist. OC affected gene transcription of lipid metabolic enzymes in keratinocytes. OC is a potential metabolic obesogen if highly accumulated in fat tissue. Abstract: Octocrylene (OC) is an extensively prescribed organic ultraviolet B filter used in sunscreen products. Due to its extensive use, a significant level of OC is detected in marine and freshwater environments. Notably, the bioaccumulation of OC in aquatic biota may affect human health. In this study, the effect of OC on metabolism was investigated using the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs). OC promoted adiponectin production during adipogenesis in hBM-MSCs compared to the vehicle-treated control (EC50, 29.6 μM). In target identification, OC directly bound to peroxisome proliferator-activated receptor (PPAR) γ ( Ki, 37.8 μM). OC-bound PPARγ also significantly recruited nuclear receptor coactivator proteins SRC-1 (EC50, 54.1 μM) and SRC-2 (EC50, 58.6 μM). In the molecular docking simulation study, the optimal ligand-binding mode of OC suggested that OC is a PPARγ partial agonist. A competitive analysis with a PPARγ full agonist pioglitazone revealed that OC acted as a PPARγ partial agonist. OC altered the gene transcription profile of lipid-metabolism associated enzymes in normal human keratinocytes, primarily exposed human cells after the application of sunscreens. In conclusion, OC is a potential metabolic disrupting obesogen.