Sunscreen filter octocrylene is a potential obesogen by acting as a PPARγ partial agonist

Toxicol Lett. 2022 Feb 1:355:141-149. doi: 10.1016/j.toxlet.2021.12.001. Epub 2021 Dec 3.

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.

Keywords: Human bone marrow mesenchymal stem cells; Obesogen; Octocrylene; Peroxisome proliferator-activated receptor gamma; UV B filter.

MeSH terms

  • Acrylates / toxicity*
  • Adipocytes / drug effects
  • Adipocytes / physiology*
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / physiology
  • Catalytic Domain
  • Gene Expression Regulation / drug effects
  • Humans
  • Keratinocytes / drug effects
  • Lipid Metabolism
  • Mesenchymal Stem Cells / drug effects*
  • Models, Molecular
  • Molecular Docking Simulation
  • Molecular Structure
  • Nuclear Receptor Coactivator 1 / genetics
  • Nuclear Receptor Coactivator 1 / metabolism
  • Nuclear Receptor Coactivator 2 / genetics
  • Nuclear Receptor Coactivator 2 / metabolism
  • Obesity / chemically induced*
  • PPAR gamma / agonists*
  • Protein Conformation

Substances

  • Acrylates
  • NCOA2 protein, human
  • Nuclear Receptor Coactivator 2
  • PPAR gamma
  • octocrylene
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1