Advertisement

Archives of Toxicology

, Volume 93, Issue 7, pp 1903–1915 | Cite as

A long-wave UVA filter avobenzone induces obesogenic phenotypes in normal human epidermal keratinocytes and mesenchymal stem cells

  • Sungjin Ahn
  • Seungchan An
  • Moonyoung Lee
  • Eunyoung Lee
  • Jeong Joo Pyo
  • Jeong Hyeon Kim
  • Min Won Ki
  • Sun Hee Jin
  • Jaehyoun Ha
  • Minsoo NohEmail author
Molecular Toxicology
  • 264 Downloads

Abstract

Avobenzone is the most commonly used ultraviolet (UV) A filter ingredient in sunscreen. To investigate the biological activity of avobenzone in normal human epidermal keratinocytes (NHEKs), the genome-scale transcriptional profile of NHEKs was performed. In this microarray study, we found 273 up-regulated and 274 down-regulated differentially expressed genes (DEGs) in NHEKs treated with avobenzone (10 μM). Gene Ontology (GO) enrichment analysis showed that avobenzone significantly increased the DEGs associated with lipid metabolism in NHEKs. In addition, avobenzone increased the gene transcription of peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid binding protein 4 in NHEKs, implicating that avobenzone may be one of the metabolic disrupting obesogens. To confirm the obesogenic potential, we examined the effect of avobenzone on adipogenesis in human bone marrow mesenchymal stem cells (hBM-MSCs). Avobenzone (EC50, 14.1 μM) significantly promoted adipogenesis in hBM-MSCs as its positive control obesogenic chemicals. Avobenzone (10 μM) significantly up-regulated mRNA levels of PPARγ during adipogenesis in hBM-MSCs. However, avobenzone did not directly bind to PPARγ and the avobenzone-induced adipogenesis-promoting activity was not affected by PPARγ antagonists T0070907 and GW9662. Therefore, avobenzone promoted adipogenesis in hBM-MSCs through a PPARγ-independent mechanism. This study suggests that avobenzone functions as a metabolic disrupting obesogen.

Keywords

Avobenzone Normal human epidermal keratinocytes Human bone marrow mesenchymal stem cells Obesogen 

Notes

Acknowledgements

This study was partly supported by the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (MSIT) (No. 2014M3C9A2064603) and the MRC grant through NRF Korea (NRF-2018R1A5A2024425).

Compliance with ethical standards

Conflict of interest

Eunyoung Lee and Jaehyoun Ha are employees of IEC Korea Inc. The other authors have no conflicts of interest.

Supplementary material

204_2019_2462_MOESM1_ESM.docx (112 kb)
Supplementary material 1 (DOCX 111 kb)

References

  1. Afonso S, Horita K, Sousa e Silva JP, Almeida IF, Amaral MH, Lobao PA, Costa PC, Miranda MS, Esteves da Silva JCG, Sousa Lobo JM (2014) Photodegradation of avobenzone: stabilization effect of antioxidants. J Photochem Photobiol B 140:36–40.  https://doi.org/10.1016/j.jphotobiol.2014.07.004 CrossRefGoogle Scholar
  2. Agrawal R, Woodfolk JA (2014) Skin barrier defects in atopic dermatitis. Curr Allergy Asthma Rep 14:433.  https://doi.org/10.1007/s11882-014-0433-9 CrossRefGoogle Scholar
  3. Ahn S, Lee M, An S, Hyun S, Hwang J, Lee J, Noh M (2018) 2-Formyl-komarovicine promotes adiponectin production in human mesenchymal stem cells through PPARγ partial agonism. Bioorg Med Chem 26:1069–1075.  https://doi.org/10.1016/j.bmc.2018.01.019 CrossRefGoogle Scholar
  4. Ahn S, Ma CT, Choi JM, An S, Lee M, Le THV, Pyo JJ, Lee J, Choi MS, Kwon SW, Park JH, Noh M (2019) Adiponectin-secretion-promoting phenylethylchromones from the agarwood of aquilaria malaccensis. J Nat Prod 82:259–264.  https://doi.org/10.1021/acs.jnatprod.8b00635 CrossRefGoogle Scholar
  5. Candi E, Schmidt R, Melino G (2005) The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 6:328–340.  https://doi.org/10.1038/nrm1619 CrossRefGoogle Scholar
  6. Chatelain E, Gabard B (2001) Photostabilization of Butyl methoxydibenzoylmethane (avobenzone) and ethylhexyl methoxycinnamate by Bis?ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), a new UV broadband filter. Photochem Photobiol 74:401–406.  https://doi.org/10.1562/0031-8655(2001)0740401POBMAA2.0.CO2 CrossRefGoogle Scholar
  7. Chen Q, Shou P, Zheng C, Jiang M, Cao G, Yang Q, Cao J, Xie N, Velletri T, Zhang X, Xu C, Zhang L, Yang H, Hou J, Wang Y, Shi Y (2016) Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell Death Differ 23:1128–1139.  https://doi.org/10.1038/cdd.2015.168 CrossRefGoogle Scholar
  8. Choi M, Park M, Lee S, Lee JW, Cho MC, Noh M, Lee C (2017) Establishment of immortalized primary human foreskin keratinocytes and their application to toxicity assessment and three dimensional skin culture construction. Biomol Ther 25:296–307.  https://doi.org/10.4062/biomolther.2017.043 CrossRefGoogle Scholar
  9. Cristancho AG, Lazar MA (2011) Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 12:722–734.  https://doi.org/10.1038/nrm3198 CrossRefGoogle Scholar
  10. ECHA (2013) Registered substances CAS 70356-09-1. https://echa.europa.eu/registration-dossier/-/registered-dossier/14835. Accessed 9 Apr 2019
  11. Feingold KR, Schmuth M, Elias PM (2007) The regulation of permeability barrier homeostasis. J Invest Dermatol 127:1574–1576.  https://doi.org/10.1038/sj.jid.5700774 CrossRefGoogle Scholar
  12. Han MH, Kim HJ, Jeong JW, Park C, Kim BW, Choi YH (2018) Inhibition of adipocyte differentiation by anthocyanins isolated from the fruit of vitis coignetiae pulliat is associated with the activation of AMPK signaling pathway. Toxicol Res 34:13.  https://doi.org/10.5487/TR.2018.34.1.013 CrossRefGoogle Scholar
  13. Harley KG, Berger K, Rauch S, Kogut K, Henn BC, Calafat AM, Huen K, Eskenazi B, Holland N (2017) Association of prenatal urinary phthalate metabolite concentrations and childhood BMI and obesity. Pediatr Res 82:405–415.  https://doi.org/10.1038/pr.2017.112 CrossRefGoogle Scholar
  14. Jansen R, Osterwalder U, Wang SQ, Burnett M, Lim HW (2013) Photoprotection: part II sunscreen: development, efficacy, and controversies. J Am Acad Dermatol 69:867.  https://doi.org/10.1016/j.jaad.2013.08.022 CrossRefGoogle Scholar
  15. Kim HJ, Lee E, Lee M, Ahn S, Kim J, Liu J, Jin SH, Ha J, Bae IH, Lee TR, Noh M (2018a) Phosphodiesterase 4B plays a role in benzophenone-3-induced phototoxicity in normal human keratinocytes. Toxicol Appl Pharmacol 338:174–181.  https://doi.org/10.1016/j.taap.2017.11.021 CrossRefGoogle Scholar
  16. Kim SO, Han Y, Ahn S, An S, Shin JC, Choi H, Kim HJ, Park NH, Kim YJ, Jin SH, Rho HS, Noh M (2018b) Kojyl cinnamate esters are peroxisome proliferator-activated receptor α/γ dual agonists. Bioorg Med Chem 26:5654–5663.  https://doi.org/10.1016/j.bmc.2018.10.010 CrossRefGoogle Scholar
  17. Lee G, Elwood F, McNally J, Weiszmann J, Lindstrom M, Amaral K, Nakamura M, Miao S, Cao P, Learned RM, Chen JL, Li Y (2002) T0070907, a selective ligand for peroxisome proliferator-activated receptor g, functions as an antagonist of biochemical and cellular activities. J Biol Chem 277:19649–19657.  https://doi.org/10.1074/jbc.M200743200 CrossRefGoogle Scholar
  18. Lee E, Kim HJ, Lee M, Jin SH, Hong SH, Ahn S, Kim SO, Shin DW, Lee ST, Noh M (2016) Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol 310:185–194.  https://doi.org/10.1016/j.taap.2016.09.017 CrossRefGoogle Scholar
  19. Lee H, Cheong KA, Kim JY, Kim NH, Noh M, Lee AY (2018a) IL-1 Receptor antagonist reduced chemical-induced keratinocyte apoptosis through antagonism to IL-1α/IL-1β. Biomol Ther 26:417–423.  https://doi.org/10.4062/biomolther.2017.167 CrossRefGoogle Scholar
  20. Lee M, Lee E, Jin SH, Ahn S, Kim SO, Kim J, Choi D, Lim KM, Lee ST, Noh M (2018b) Leptin regulates the pro-inflammatory response in human epidermal keratinocytes. Arch Dermatol Res 310:351–362.  https://doi.org/10.1007/s00403-018-1821-0 CrossRefGoogle Scholar
  21. Lin TK, Zhong L, Santiago J (2017) Anti-inflammatory and skin barrier repair effects of topical application of some plant oils. Int J Mol Sci 19:70.  https://doi.org/10.3390/ijms19010070 CrossRefGoogle Scholar
  22. Lv Z, Cheng J, Huang S, Zhang Y, Wu S, Qiu Y, Geng Y, Zhang Q, Huang G, Ma Q, Xie X, Zhou S, Wu T, Ke Y (2016) DEHP induces obesity and hypothyroidism through both central and peripheral pathways in C3H/He mice. Obesity 24:368–378.  https://doi.org/10.1002/oby.21359 CrossRefGoogle Scholar
  23. Matsui T, Amagai M (2015) Dissecting the formation, structure and barrier function of the stratum corneum. Int Immunol 27:269–280.  https://doi.org/10.1093/intimm/dxx024 CrossRefGoogle Scholar
  24. Motley RJ, Reynolds AJ (1989) Photocontact dermatitis due to isopropyl and butyl methoxy dibenzoylmethanes (eusolex 8020 and parsol 1789). Contact Dermatitis 21:109–110.  https://doi.org/10.1111/j.1600-0536.1989.tb04708.x CrossRefGoogle Scholar
  25. Muscogiuri G, Barrea L, Laudisio D, Savastano S, Colao A (2017) Obesogenic endocrine disruptors and obesity: myths and truths. Arch Toxicol 91:3469–3475.  https://doi.org/10.1007/s00204-017-2071-1 CrossRefGoogle Scholar
  26. Noh M (2012) Interleukin-17A increases leptin production in human bone marrow mesenchymal stem cells. Biochem Pharmacol 83:661–670.  https://doi.org/10.1016/j.bcp.2011.12.010 CrossRefGoogle Scholar
  27. OECD (2014) Detailed review paper on the state of the science on novel in vitro and in vivo screening and testing methods and endpoints for evaluating endocrine disruptors, OECD Series on Testing and Assessment, No. 178, OECD Publishing, Paris.  https://doi.org/10.1787/9789264221352-en
  28. Pereira-Fernandes A, Vanparys C, Vergauwen L, Knapen D, Jorens PG, Blust R (2014) Toxicogenomics in the 3T3-L1 cell line, a new approach for screening of obesogenic compounds. Toxicol Sci 140:352–363.  https://doi.org/10.1093/toxsci/kfu092 CrossRefGoogle Scholar
  29. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res 29:e45.  https://doi.org/10.1093/nar/29.9.e45 CrossRefGoogle Scholar
  30. Piao MJ, Ahn MJ, Kang KA, Ryu YS, Hyun YJ, Shilnikova K, Zhen AX, Jeong JW, Choi YH, Kang HK, Koh YS, Hyun JW (2018) Particulate matter 2.5 damages skin cells by inducing oxidative stress, subcellular organelle dysfunction, and apoptosis. Arch Toxicol 92:2077–2091.  https://doi.org/10.1007/s00204-018-2197-9 CrossRefGoogle Scholar
  31. Poiger T, Buser HR, Balmer ME, Bergqvist PA, Muller MD (2004) Occurrence of UV filter compounds from sunscreens in surface waters: regional mass balance in two Swiss lakes. Chemosphere 55:951–963.  https://doi.org/10.1016/j.chemosphere.2004.01.012 CrossRefGoogle Scholar
  32. Ramos S, Homem V, Alves A, Santos L (2015) Advances in analytical methods and occurrence of organic UV-filters in the environment-a review. Sci Total Environ 526:278–311.  https://doi.org/10.1016/j.scitotenv.2015.04.055 CrossRefGoogle Scholar
  33. Roth W, Kumar V, Beer HD, Richter M, Wohlenberg C, Reuter U, Thiering S, Staratschek-Jox A, Hofmann A, Kreusch F, Schultze JL, Vogl T, Roth J, Reichelt J, Hausser I, Magin TM (2012) Keratin 1 maintains skin integrity and participates in an inflammatory network in skin through interleukin-18. J Cell Sci 125:5269–5279.  https://doi.org/10.1242/jcs.116574 CrossRefGoogle Scholar
  34. Ruiz-Ojeda FJ, Ruperez AI, Gomez-Llorente C, Gil A, Aguilera CM (2016) Cell models and their application for studying adipogenic differentiation in relation to obesity: a review. Int J Mol Sci 17:1040.  https://doi.org/10.3390/ijms17071040 CrossRefGoogle Scholar
  35. Samuelov L, Sprecher E (2014) Peeling off the genetics of atopic dermatitis–like congenital disorders. J Allergy Clin Immunol 134:808–815.  https://doi.org/10.1016/j.jaci.2014.07.061 CrossRefGoogle Scholar
  36. Sayre RM, Dowdy JC, Gerwig AJ, Shlelds WJ, Lioyd RV (2005) Unexpected photolysis of the sunscreen octinoxate in the presence of the sunscreen avobenzone. Photochem Photobiol 81:452–456.  https://doi.org/10.1111/j.1751-1097.2005.tb00207.x CrossRefGoogle Scholar
  37. Scott MA, Nguyen VT, Levi B, James AW (2011) Current methods of adipogenic differentiation of mesenchymal stem cells. Stem Cells Dev 20:1793–1804.  https://doi.org/10.1089/scd.2011.0040 CrossRefGoogle Scholar
  38. Sever N, Yang T, Brown MS, Goldstein JL, DeBose-Boyd RA (2003) Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain. Mole cell 11:25–33.  https://doi.org/10.1016/S1097-2765(02)00822-5 CrossRefGoogle Scholar
  39. Shin JH, Shin DW, Noh M (2009) Interleukin-17A inhibits adipocyte differentiation in human mesenchymal stem cells and regulates pro-inflammatory responses in adipocytes. Biochem Pharmacol 77:1835–1844.  https://doi.org/10.1016/j.bcp.2009.03.008 CrossRefGoogle Scholar
  40. Uter W, Goncalo M, Yazar K, Kratz EM, Mildau G, Liden C (2014) Coupled exposure to ingredients of cosmetic products: III. Ultraviolet filters. Contact Dermat 71:162–169.  https://doi.org/10.1111/cod.12245 CrossRefGoogle Scholar
  41. Van Smeden J, Janssens M, Gooris GS, Bouwstra JA (2014) The important role of stratum corneum lipids for the cutaneous barrier function. BBA-Mol Cell Biol L 1841:295–313.  https://doi.org/10.1016/j.bbalip.2013.11.006 CrossRefGoogle Scholar
  42. Varga T, Czimmerer Z, Nagy L (2011) PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. BBA-Mol Basis Dis 1812:1007–1022.  https://doi.org/10.1016/j.bbadis.2011.02.014 CrossRefGoogle Scholar
  43. Veiga-Lopez A, Pu Y, Gingrich J, Padmanabhan V (2018) Obesogenic endocrine disrupting chemicals: identifying knowledge gaps. Trends Endocrinol Metab 29:607–625.  https://doi.org/10.1016/j.tem.2018.06.003 CrossRefGoogle Scholar
  44. Wahli W, Michalik L (2012) PPARs at the crossroads of lipid signaling and inflammation. Trends Endocrinol Metab 23:351–363.  https://doi.org/10.1016/j.tem.2012.05.001 CrossRefGoogle Scholar
  45. Wang SQ, Lim HW (2011) Current status of the sunscreen regulation in the United States: 2011 food and drug administration’s final rule on labeling and effectiveness testing. J Am Acad Dermatol 65:863–869.  https://doi.org/10.1016/j.jaad.2011.07.025 CrossRefGoogle Scholar
  46. Wang SQ, Xu H, Stanfield JW, Osterwalder U, Herzog B (2017) Comparison of ultraviolet A light protection standards in the United States and European union through in vitro measurements of commercially available sunscreens. J Am Acad Dermatol 77:42–47.  https://doi.org/10.1016/j.jaad.2017.01.017 CrossRefGoogle Scholar
  47. Yu J, Ahn S, Kim HJ, Lee M, Ahn S, Kim J, Jin SH, Lee E, Kim G, Cheong JH, Jacobson KA, Jeong LS, Noh M (2017) Polypharmacology of N 6-(3-Iodobenzyl) adenosine-5′-N-methyluronamide (IB-MECA) and related A3 adenosine receptor ligands: peroxisome proliferator activated receptor (PPAR) γ partial agonist and PPARδ antagonist activity suggests their antidiabetic potential. J Med Chem 60:7459–7475.  https://doi.org/10.1021/acs.jmedchem.7b00805 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of PharmacySeoul National UniversitySeoulRepublic of Korea
  2. 2.Natural Products Research Institute, College of PharmacySeoul National UniversitySeoulRepublic of Korea
  3. 3.Toxicology DivisionIEC KoreaSuwonRepublic of Korea

Personalised recommendations