Rapamycin Inhibits Expression of Elongation of Very-long-chain Fatty Acids 1 and Synthesis of Docosahexaenoic Acid in Bovine Mammary Epithelial Cells

  • Guo, Zhixin (College of Life Science, Inner Mongolia University) ;
  • Wang, Yanfeng (College of Life Science, Inner Mongolia University) ;
  • Feng, Xue (College of Life Science, Inner Mongolia University) ;
  • Bao, Chaogetu (College of Life Science, Inner Mongolia University) ;
  • He, Qiburi (College of Life Science, Inner Mongolia University) ;
  • Bao, Lili (College of Basic Medical Science, Inner Mongolia Medical University) ;
  • Hao, Huifang (College of Life Science, Inner Mongolia University) ;
  • Wang, Zhigang (College of Life Science, Inner Mongolia University)
  • Received : 2015.08.08
  • Accepted : 2016.01.05
  • Published : 2016.11.01


Mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth and metabolism and is sufficient to induce specific metabolic processes, including de novo lipid biosynthesis. Elongation of very-long-chain fatty acids 1 (ELOVL1) is a ubiquitously expressed gene and the product of which was thought to be associated with elongation of carbon (C) chain in fatty acids. In the present study, we examined the effects of rapamycin, a specific inhibitor of mTORC1, on ELOVL1 expression and docosahexaenoic acid (DHA, C22:6 n-3) synthesis in bovine mammary epithelial cells (BMECs). We found that rapamycin decreased the relative abundance of ELOVL1 mRNA, ELOVL1 expression and the level of DHA in a time-dependent manner. These data indicate that ELOVL1 expression and DHA synthesis are regulated by mTORC1 in BMECs.


Supported by : Natural Sciences Foundation of China, Natural Science Foundation of Inner Mongolia Autonomous Region of china, innovation team from Inner Mongolia


  1. Benoit, B., J. Bruno, F. Kayal, M. Estienne, C. Debard, R. Ducroc, and P. Plaisancie. 2015. Saturated and unsaturated fatty acids differently modulate colonic goblet cells in vitro and in rat pups. J. Nutr. 145:1754-1762.
  2. Carmona-Antonanzas, G., D. R. Tocher, L. Martinez-Rubio, and M. J. Leaver. 2014. Conservation of lipid metabolic gene transcriptional regulatory networks in fish and mammals. Gene 534:1-9.
  3. Duvel, K., J. L. Yecies, S. Menon, P. Raman, A. I. Lipovsky, A. L. Souza, E. Triantafellow, Q. Ma, R. Gorski, and S. Cleaver et al. 2010. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol. Cell 39:171-183.
  4. German, J. B. and C. J. Dillard. 2006. Composition, structure and absorption of milk lipids: A source of energy, fatsoluble nutrients, and bioactive molecules. Crit. Rev. Food Sci. Nutr. 46:57-92.
  5. Hartmann, D., M. S. Wegner, R. A. Wanger, N. Ferreiros, Y. Schreiber, J. Lucks, S. Schiffmann, G. Geisslinger, and S. Grosch. 2013. The equilibrium between long and very long chain ceramides is important for the fate of the cell and can be influenced by co-expression of CerS. Int. J. Biochem. Cell Biol. 45:1195-1203.
  6. Jakobsson, A., R. Westerberg, and A. Jacobsson. 2006. Fatty acid elongases in mammals: Their regulation and roles in metabolism. Prog. Lipid Res. 45:237-249.
  7. Jensen, R. G., A. M. Ferris, and C. J. Lammi-Keefe. 1991. The composition of milk fat. J. Dairy Sci. 74:3228-3243.
  8. Kihara, A. 2012. Very long-chain fatty acids: Elongation, physiology and related disorders. J. Biochem. 152:387-395.
  9. Kozawa, S., A. Honda, N. Kajiwara, Y. Takemoto, T. Nagase, H. Nikami, Y. Okano, S. Nakashima, and N. Shimozawa. 2011. Induction of peroxisomal lipid metabolism in mice fed a highfat diet. Mol. Med. Rep. 4:1157-1162.
  10. Laplante, M. and D. M. Sabatini. 2012. mTOR signaling in growth control and disease. Cell 149:274-293.
  11. Lamming, D. W. and D. M. Sabatini. 2013. A central role for mTOR in lipid homeostasis. Cell Metab. 18:465-469.
  12. Laplante, M. and D. M. Sabatini. 2013. Regulation of mTORC1 and its impact on gene expression at a glance. J. Cell Sci. 126:1713-1719.
  13. Li, N., F. Zhao, C. Wei, M. Liang, N. Zhang, C. Wang, Q. Z. Li, and X. J. Gao. 2014. Function of SREBP1 in the milk fat synthesis of dairy cow mammary epithelial cells. Int. J. Mol. Sci. 15:16998-17013.
  14. Lodhi, I. J., X. Wei, and C. F. Semenkovich. 2011. Lipoexpediency: de novo lipogenesis as a metabolic signal transmitter. Trends Endocrinol. Metab. 22:1-8.
  15. McFadden, J. W. and B. A. Corl. 2009. Activation of AMPactivated protein kinase (AMPK) activation of inhibits fatty acid synthesis in bovine mammary epithelial cells. Biochem. Biophys. Res. Commun. 390:388-393.
  16. Nogalski, Z., M. Wronski, M. Sobczuk-Szul, M. Mochol, and P. Pogorzelska. 2012. The effect of body energy reserve mobilization on the fatty acid profile of milk in high-yielding cows. Asian Australas J. Anim. Sci. 25:1712-1720.
  17. Ofman, R. and I. M. E. Dijkstra. 2010. The role of ELOVL1 in very long-chain fatty acid homeostasis and X-linked adrenoleukodystrophy. EMBO Mol. Med. 2:90-97.
  18. Ohno, Y., S. Suto, M. Yamanaka, Y. Mizutani, S. Mitsutake, Y. Igarashi, T. Sassa, and A. Kihara. 2010. ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis. Proc. Natl. Acad. Sci. USA. 107:18439-18444.
  19. Qi, L., S. Yan, R. Sheng, Y. Zhao, and X. Guo. 2014. Effects of saturated long-chain fatty acid on mRNA expression of genes associated with milk fat and protein biosynthesis in bovine mammary epithelial cells. Asian Australas. J. Anim. Sci. 27:414-421.
  20. Sassa, T. and A. Kihara. 2014. Metabolism of very long-chain fatty acids: Genes and pathophysiology. Biomol. Ther. (Seoul) 22:83-92.
  21. Sassa, T., T. Wakashima, Y. Ohno, and A. Kihara. 2014. Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid. J. Lipid Res. 55:524-530.
  22. Soliman, G. A. 2011. The integral role of mTOR in lipid metabolism. Cell Cycle. 10:861-862.
  23. Tvrdik, P., R. Westerberg, S. Silve, A. Asadi, A. Jakobsson, B. Cannon, G. Loison, and A. Jacobsson. 2000. Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids. J. Cell Biol. 149:707-718.
  24. Wang, Q., M. Tikhonenko, S. N. Bozack, T. A. Lydic, L. Yan, N. L. Panchy, K. M. Mcsorley, M. S. Faber, Y. Yan, M. E. Boulton, M. B. Grant, and J. V. Busik, 2014a. Changes in the daily rhythm of lipid metabolism in the diabetic retina. PLoS One. 9:e95028. doi: 10.1371/journal.pone.0095028. eCollection 2014.
  25. Wang, X., L. Xiu, Q. Hu, X. Cui, B. Liu, L. Tao, T. Wang, J. Wu, Y. Chen, and Y. Chen. 2013. Deep sequencing-based transcriptional analysis of bovine mammary epithelial cells gene expression in response to in vitro infection with staphylococcus aureus stains. PLoS One. 8:e82117.
  26. Wang, Y., D. Botolin, J. Xu, B. Christian, E. Mitchell, B. Jayaprakasam, M. G. Nair, J. M. Peters, J. V. Busik, L. K. Olson, and D. B. Jump. 2006. Regulation of hepatic fatty acid elongase and desaturase expression in diabetes and obesity. J. Lipid Res. 47:2028-2041.
  27. Wang, Z., X. Hou, B. Qu, J. Wang, X. Gao, and Q. Li. 2014b. Pten regulates development and lactation in the mammary glands of dairy cows. PLoS One. 9:e102118. doi: 10.1371/journal.pone.0102118. eCollection 2014.
  28. Xue, X., C. Y. Feng, S. M. Hixson, K. Johnstone, D. M. Anderson, C. C. Parrish, and M. L. Rise. 2014. Characterization of the fatty acyl elongase (ELOVL) gene family, and hepatic elovl and delta-6 fatty acyl desaturase transcript expression and fatty acid responses to diets containing camelina oil in Atlantic cod (Gadus morhua). Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 175:9-22.
  29. Yu, C., C. Luo, B. Qu, N. Khudhair, X. Gu, Y. Zang, C. Wang, N. Zhang, Q. Li, and X. Gao. 2014. Molecular network including eIF1AX, RPS7, and 14-3-$3{\gamma}$ regulates protein translation and cell proliferation in bovine mammary epithelial cells. Arch. Biochem. Biophys. 564:142-155.
  30. Zhang, X., F. Zhao, Y. Si, Y. Huang, C. Yu, C. Luo, N. Zhang, Q. Li, and X. Gao. 2014. $GSK3{\beta}$ regulates milk synthesis in and proliferation of dairy cow mammary epithelial cells via the mTOR/S6K1 signaling pathway. Molecules 19:9435-9452.