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防晒霜成分奥克立林作为一种过氧化物酶体增殖物激活受体 γ 部分激动剂,可能是一种致肥胖物。

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

机构信息

Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.

College of Pharmacy, Dongguk University-Seoul, 32 Dongguk-ro, Goyang, Gyeonggi-do, 10326, Republic of Korea.

出版信息

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

DOI:10.1016/j.toxlet.2021.12.001
PMID:34864131
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 (EC, 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 (EC, 54.1 μM) and SRC-2 (EC, 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.

摘要

辛氧苯酮(OC)是一种广泛应用于防晒霜产品的有机紫外线 B 过滤剂。由于其广泛使用,OC 在海洋和淡水环境中被大量检测到。值得注意的是,OC 在水生生物群中的生物蓄积可能会影响人类健康。在这项研究中,使用人骨髓间充质干细胞(hBM-MSCs)的脂肪生成模型研究了 OC 对代谢的影响。与溶剂处理对照组(EC,29.6μM)相比,OC 在 hBM-MSCs 的脂肪生成过程中促进脂联素的产生。在靶标鉴定中,OC 直接与过氧化物酶体增殖物激活受体(PPAR)γ结合(Ki,37.8μM)。OC 结合的 PPARγ 还显著募集核受体共激活蛋白 SRC-1(EC,54.1μM)和 SRC-2(EC,58.6μM)。在分子对接模拟研究中,OC 的最佳配体结合模式表明 OC 是一种 PPARγ 部分激动剂。与 PPARγ 完全激动剂吡格列酮的竞争性分析表明,OC 是一种 PPARγ 部分激动剂。OC 改变了正常人类角质形成细胞中与脂质代谢相关酶的基因转录谱,这些酶主要是在应用防晒霜后暴露于人细胞。总之,OC 是一种潜在的代谢性肥胖干扰物。

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