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Palmitic acid induces inflammatory cytokines and regulates tRNA-derived stress-induced RNAs in human trophoblasts

  • Changwon, Yang (Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Garam, An (Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Jisoo, Song (Department of Biological Sciences, Sungkyunkwan University) ;
  • Gwonhwa, Song (Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Whasun, Lim (Department of Biological Sciences, Sungkyunkwan University)
  • Received : 2022.09.01
  • Accepted : 2022.09.08
  • Published : 2022.12.31

Abstract

High levels of proinflammatory cytokines have been observed in obese pregnancies. Obesity during pregnancy may increase the risk of various pregnancyrelated complications, with pathogenesis resulting from excessive inflammation. Palmitic acid (PA) is a saturated fatty acid that circulates in high levels in obese women. In our previous study, we found that PA inhibited the proliferation of trophoblasts developing into the placenta, induced apoptosis, and regulated the number of cleaved halves derived from transfer RNAs (tRNAs). However, it is not known how the expression of tRNA-derived stress-induced RNAs (tiRNAs) changes in response to PA treatment at concentrations that induce inflammation in human trophoblasts. We selected concentrations that did not affect cell viability after dose-dependent treatment of HTR8/SVneo cells, a human trophoblast cell line. PA (200 μM) did not affect the expression of apoptotic proteins in HTR8/SVneo cells. PA significantly increased the expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α. In addition, 200 μM PA significantly increased the expression of tiRNAs compared to 800 μM PA treatment. These results suggest that PA impairs placental development during early pregnancy by inducing an inflammatory response in human trophoblasts. In addition, this study provides a basis for further research on the association between PA-induced inflammation and tiRNA generation.

Keywords

Acknowledgement

This study was supported by the Institute of Animal Molecular Biotechnology, Korea University. This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (grant number: 2018R1C1B6009048).

References

  1. Abrahams VM. 2011. The role of the Nod-like receptor family in trophoblast innate immune responses. J. Reprod. Immunol. 88:112-117. https://doi.org/10.1016/j.jri.2010.12.003
  2. Amine H, Benomar Y, Taouis M. 2021. Palmitic acid promotes resistin-induced insulin resistance and inflammation in SHSY5Y human neuroblastoma. Sci. Rep. 11:5427. (Erratum published 2021, Sci. Rep. 11:12935)
  3. Bae H, Yang C, Lee JY, Park S, Bazer FW, Song G, Lim W. 2020. Melatonin improves uterine-conceptus interaction via regulation of SIRT1 during early pregnancy. J. Pineal Res. 69:e12670.
  4. Challier JC, Basu S, Bintein T, Minium J, Hotmire K, Catalano PM, Hauguel-de Mouzon S. 2008. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 29:274-381. https://doi.org/10.1016/j.placenta.2007.12.010
  5. Chen X, Scholl TO, Leskiw M, Savaille J, Stein TP. 2010. Differences in maternal circulating fatty acid composition and dietary fat intake in women with gestational diabetes mellitus or mild gestational hyperglycemia. Diabetes Care 33:2049-2054. https://doi.org/10.2337/dc10-0693
  6. Choi J, Yang C, Lim W, Song G, Choi H. 2022. Antioxidant and apoptotic activity of cocoa bean husk extract on prostate cancer cells. Mol. Cell. Toxicol. 18:193-203. https://doi.org/10.1007/s13273-021-00187-w
  7. Colvin BN, Longtine MS, Chen B, Costa ML, Nelson DM. 2017. Oleate attenuates palmitate-induced endoplasmic reticulum stress and apoptosis in placental trophoblasts. Reproduction 153:369-380. https://doi.org/10.1530/REP-16-0576
  8. Eastman AJ, Moore RE, Townsend SD, Gaddy JA, Aronoff DM. 2021. The influence of obesity and associated fatty acids on placental inflammation. Clin. Ther. 43:265-278. https://doi.org/10.1016/j.clinthera.2020.12.018
  9. Joshi-Barve S, Barve SS, Amancherla K, Gobejishvili L, Hill D, Cave M, Hote P, McClain CJ. 2007. Palmitic acid induces production of proinflammatory cytokine interleukin-8 from hepatocytes. Hepatology 46:823-830. https://doi.org/10.1002/hep.21752
  10. Korbecki J and Bajdak-Rusinek K. 2019. The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms. Inflamm. Res. 68:915-932. https://doi.org/10.1007/s00011-019-01273-5
  11. Lyons SM, Fay MM, Ivanov P. 2018. The role of RNA modifications in the regulation of tRNA cleavage. FEBS Lett. 592: 2828-2844. https://doi.org/10.1002/1873-3468.13205
  12. Madan JC, Davis JM, Craig WY, Collins M, Allan W, Quinn R, Dammann O. 2009. Maternal obesity and markers of inflammation in pregnancy. Cytokine 47:61-64. https://doi.org/10.1016/j.cyto.2009.05.004
  13. Manuel CR, Charron MJ, Ashby CR Jr, Reznik SE. 2018. Saturated and unsaturated fatty acids differentially regulate in vitro and ex vivo placental antioxidant capacity. Am. J. Reprod. Immunol. 80:e12868.
  14. Marques-Rocha JL, Samblas M, Milagro FI, Bressan J, Martinez JA, Marti A. 2015. Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB J. 29:3595-3611. https://doi.org/10.1096/fj.14-260323
  15. Mor G. 2008. Inflammation and pregnancy: the role of toll-like receptors in trophoblast-immune interaction. Ann. N. Y. Acad. Sci. 1127:121-128. https://doi.org/10.1196/annals.1434.006
  16. Natarajan SK, Bruett T, Muthuraj PG, Sahoo PK, Power J, Mott JL, Hanson C, Anderson-Berry A. 2021. Saturated free fatty acids induce placental trophoblast lipoapoptosis. PLoS One 16:e0249907.
  17. Pan L, Huang X, Liu ZX, Ye Y, Li R, Zhang J, Wu G, Bai R, Zhuang L, Wei L, Li M, Zheng Y, Su J, Deng J, Deng S, Zeng L, Zhang S, Wu C, Che X, Wang C, Chen R, Lin D, Zheng J. 2021. Inflammatory cytokine-regulated tRNA-derived fragment tRF-21 suppresses pancreatic ductal adenocarcinoma progression. J. Clin. Invest. 131:e148130.
  18. Park H, Song G, Lim W. 2021. Isoprocarb induces acute toxicity in developing zebrafish embryos through vascular malformation. J. Anim. Reprod. Biotechnol. 36:17-24. https://doi.org/10.12750/JARB.36.1.17
  19. Saikia M, Krokowski D, Guan BJ, Ivanov P, Parisien M, Hu GF, Anderson P, Pan T, Hatzoglou M. 2012. Genome-wide identification and quantitative analysis of cleaved tRNA fragments induced by cellular stress. J. Biol. Chem. 287:42708-42725. https://doi.org/10.1074/jbc.M112.371799
  20. Sano M, Shimazaki S, Kaneko Y, Karasawa T, Takahashi M, Ohkuchi A, Takahashi H, Kurosawa A, Torii Y, Iwata H, Kuwayama T, Shirasuna K. 2020. Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice. J. Reprod. Dev. 66:241-248. https://doi.org/10.1262/jrd.2020-007
  21. Schenk S, Saberi M, Olefsky JM. 2008. Insulin sensitivity: modulation by nutrients and inflammation. J. Clin. Invest. 118: 2992-3002. https://doi.org/10.1172/JCI34260
  22. Simko M, Totka A, Vondrova D, Samohyl M, Jurkovicova J, Trnka M, Cibulkova A, Stofko J, Argalasova L. 2019. Maternal body mass index and gestational weight gain and their association with pregnancy complications and perinatal conditions. Int. J. Environ. Res. Public Health 16:1751.
  23. Su Z, Frost EL, Lammert CR, Przanowska RK, Lukens JR, Dutta A. 2020. tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immuneactivation autism model. RNA Biol. 17:1183-1195. https://doi.org/10.1080/15476286.2020.1721047
  24. Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP. 2011. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat. Immunol. 12:408-415. https://doi.org/10.1038/ni.2022
  25. Yamasaki S, Ivanov P, Hu GF, Anderson P. 2009. Angiogenin cleaves tRNA and promotes stress-induced translational repression. J. Cell Biol. 185:35-42. https://doi.org/10.1083/jcb.200811106
  26. Yang C, Bae H, Song G, Lim W. 2020. Quercetin affects spermatogenesis-related genes of mouse exposed to high-cholesterol diet. J. Anim. Reprod. Biotechnol. 35:73-85. https://doi.org/10.12750/JARB.35.1.73
  27. Yang C, Lim W, Bazer FW, Song G. 2017. Oleic acid stimulation of motility of human extravillous trophoblast cells is mediated by stearoyl-CoA desaturase-1 activity. Mol. Hum. Reprod. 23:755-770. https://doi.org/10.1093/molehr/gax051
  28. Yang C, Lim W, Bazer FW, Song G. 2018. Down-regulation of stearoyl-CoA desaturase-1 increases susceptibility to palmitic-acid-induced lipotoxicity in human trophoblast cells. J. Nutr. Biochem. 54:35-47. https://doi.org/10.1016/j.jnutbio.2017.11.005
  29. Yang C, Lim W, Park J, Park S, You S, Song G. 2019. Anti-inflammatory effects of mesenchymal stem cell-derived exosomal microRNA-146a-5p and microRNA-548e-5p on human trophoblast cells. Mol. Hum. Reprod. 25:755-771. https://doi.org/10.1093/molehr/gaz054
  30. Yang C, Park S, Song G, Lim W. 2022. Inhibition of the cleaved half of tRNAGly enhances palmitic acid-induced apoptosis in human trophoblasts. J. Nutr. Biochem. 99:108866.
  31. Yin A, Chen Q, Zhong M, Jia B. 2021. MicroRNA-138 improves LPS-induced trophoblast dysfunction through targeting RELA and NF-κB signaling. Cell Cycle 20:508-521. https://doi.org/10.1080/15384101.2021.1877927
  32. Zhang Y, Ren L, Sun X, Zhang Z, Liu J, Xin Y, Yu J, Jia Y, Sheng J, Hu GF, Zhao R, He B. 2021. Angiogenin mediates paternal inflammation-induced metabolic disorders in offspring through sperm tsRNAs. Nat. Commun. 12:6673.
  33. Zhong F, Hu Z, Jiang K, Lei B, Wu Z, Yuan G, Luo H, Dong C, Tang B, Zheng C, Yang S, Zeng Y, Guo Z, Yu S, Su H, Zhang G, Qiu X, Tomlinson S, He S. 2019. Complement C3 activation regulates the production of tRNA-derived fragments GlytRFs and promotes alcohol-induced liver injury and steatosis. Cell Res. 29:548-561. https://doi.org/10.1038/s41422-019-0175-2