DOI QR코드

DOI QR Code

Aerobic Exercise Ameliorated High Fat Diet-induced Endoplasmic Reticulum Stress More Than Polyphenol Supplementation in Skeletal Muscle of Obese Mice

비만에 의해 유도된 근형질세망 스트레스에서 유산소 운동에 의한 감소효과

  • Park, Jong-Gu (Department of Sport Science, Chungnam National University) ;
  • Kim, Yong-An (Institute of Biotechnology, Chungnam National University) ;
  • Park, Hee-Geun (Department of Sport Science, Chungnam National University) ;
  • Lee, Wang-Lok (Department of Sport Science, Chungnam National University)
  • 박종구 (충남대학교 스포츠과학과) ;
  • 김용안 (충남대학교 생물공학연구소) ;
  • 박희근 (충남대학교 스포츠과학과) ;
  • 이왕록 (충남대학교 스포츠과학과)
  • Received : 2018.06.04
  • Accepted : 2018.10.24
  • Published : 2018.10.30

Abstract

The purpose of this study was to compare the effects of either aerobic exercise or polyphenols supplementation on mRNA expression of endoplasmic reticulum stress in skeletal muscle of high fat diet-induced obese mice. In the study, mice were divided into five groups: (1) NC (normal diet for 16 weeks as a control, n=10), (2) HC (high fat diet for 16 weeks as a control, n=10), (3) H-Re (high fat diet with resveratrol 25 mg/kg supplementation for 16 weeks, n=10), (4) H-Ch (high fat diet with chrysin 50 mg/kg supplementation for 16 weeks, n=10), and (5) HE (high fat diet with aerobic exercise for 16 weeks, n=10). Aerobic exercise was performed on a treadmill for 40~60 min/day at 10~14 m/min, 0% grade, four days/week for 16 weeks. Endoplasmic reticulum stress related genes were measured by real-time polymerase chain reaction. ATF6, PERK, $IRE1{\alpha}$, and BIP/GRP78 mRNA were significantly decreased in HE compared with those in HC (p<0.05). Also, ATF6, $IRE1{\alpha}$, and BIP/GRP78 mRNA were significantly decreased in H-Re compared with those in HC (p<0.05). ATF6 mRNA was significantly decreased in H-Ch compared with that in HC (p<0.05). These findings suggest that aerobic exercise, resveratrol, and chrysin supplementation changed ER stress markers. However, aerobic exercise was most effective on ameliorating the high fat diet induced ER stress markers. Thus, it seems that aerobic exercise might have a more positive effect on skeletal muscle endoplasmic reticulum stress compared with polyphenol supplementation in high fat diet-induced obese mice.

비만에 의한 근형질세망 스트레스(Endoplasmic stress, ER stress) 발생은 비접힙 단백질의 축적으로 근육내 대사와 근기능 저하를 초래한다. 유산소 운동과 폴리페놀은 비만에 유도된 염증성 사이토카인과 ER stress를 감소시키는 것으로 잘 알려졌다. 그러나 신체활동과 약물에 의한 염증성 사이토카인과 ER stress 변인들의 변화에 선택적인 반응이 있는지에 대한 연구는 이루어지지 않았다. 따라서, 이 연구의 목적은 유산소 운동과 폴리페놀섭취에 따른 골격근내 ER stress 관련 변인에 우선적인 효과가 있는지 비교분석하고자 하였다. 이 연구의 목적을 위해 (1) 정상식이 그룹, (2) 60% 고지방식이 그룹, (3) 고지방식와 레스베라트롤 25 mg/kg 그룹, (4) 고지방식이와 크리신 50 mg/kg 투여 그룹, (5) 고지방식이와 운동 그룹으로 나누어 실시하였다. 레스베라트롤과 크리신 그룹은 16주간 경구 투여 하였고, 운동 그룹은 1일 40-60분간 10-14 m/min의 속도로 주 4일, 총 16주간 트레드밀 운동을 수행하였다. 운동그룹에서 $IRE1{\alpha}$, BIP/GRP78는 고지방 식이 그룹과 비교하여 유의하게 낮아졌다(p<0.05). 고지방식이와 레스베라트롤 투여 그룹에서 ATF6, $IRE1{\alpha}$, BIP/GRP78는 고지방식이 그룹과 비교하여 유의하게 낮아졌다(p<0.05). 고지방식이와 크리신 투여 그룹은 고지방식이 그룹과 비교하여 ATF6가 유의하게 낮아졌다(p<0.05). 이러한 결과는 유산소 운동과 레스베라트롤, 크리신 섭취에 의해 ER stress 관련 변인을 조절할 수 있다. 그러나 유산소 운동은 고지방 식이에 의해 유도되는 ER stress 개선이 더욱 효과적인 것으로 나타났다.

Keywords

References

  1. Borg, M. L., Omran, S. F., Weir, J., Meikle, P. J. and Watt, M. J. 2012. Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice. J. Physiol. 590, 4377-4389. https://doi.org/10.1113/jphysiol.2012.233288
  2. Chapados, N. A. and Lavoie, J. M. 2010. Exercise training increases hepatic endoplasmic reticulum (er) stress protein expression in MTP-inhibited high-fat fed rats. Cell Biochem. Funct. 28, 202-210. https://doi.org/10.1002/cbf.1643
  3. Cnop, M., Foufelle, F. and Velloso, L. A. 2012. Endoplasmic reticulum stress, obesity and diabetes. Trends Mol. Med. 18, 59-68. https://doi.org/10.1016/j.molmed.2011.07.010
  4. Dekker, M. J., Su, Q., Baker, C., Rutledge, A. C. and Adeli, K. 2010. Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome. American journal of physiology. Am. J. Physiol. Endocrinol. Metab. 299, E685-E694. https://doi.org/10.1152/ajpendo.00283.2010
  5. Deldicque, L., Bertrand, L., Patton, A., Francaux, M. and Baar, K. 2011. ER stress induces anabolic resistance in muscle cells through PKB-induced blockade of mTORC1. PLoS One 6, e20993.
  6. Deldicque, L., Hespel, P. and Francaux, M. 2012. Endoplasmic reticulum stress in skeletal muscle: origin and metabolic consequences. Exerc. Sport Sci. Rev. 40, 43-49. https://doi.org/10.1097/JES.0b013e3182355e8c
  7. Fonseca, S. G., Gromada, J. and Urano, F. 2011. Endoplasmic reticulum stress and pancreatic beta-cell death. Trends Endocrinol. Metab. 22, 266-274.
  8. Fribley, A., Zhang, K. and Kaufman, R. J. 2009. Regulation of apoptosis by the unfolded protein response. Methods Mol. Biol. 559, 191-204.
  9. Gregor, M. F., Yang, L., Fabbrini, E., Mohammed, B. S. and Eagon, J. C. 2009. Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss. Diabetes 58, 693-700.
  10. Hendershot, L. M. 2004. The ER function BiP is a master regulator of ER function. Mt Sinai J. Med. 71, 289-297.
  11. Hotamisligil, G. S. 2010. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140, 900-917. https://doi.org/10.1016/j.cell.2010.02.034
  12. Jiao, P., Ma, J., Feng, B., Zhang, H. and Diehl, J. A. 2011. FFA-induced adipocyte inflammation and insulin resistance: involvement of ER stress and IKKbeta pathways. Obesity (Silver Spring) 19, 483-491. https://doi.org/10.1038/oby.2010.200
  13. Li, Y., Xu, S., Giles, A., Nakamura, K. and Lee, J. W. 2011. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB J. 25, 1664-1679. https://doi.org/10.1096/fj.10-173492
  14. Mauthe, M., Jacob, A., Freiberger, S., Hentschel, K. and Stierhof, Y. D. 2011. Resveratrol-mediated autophagy requires WIPI-1-regulated LC3 lipidation in the absence of induced phagophore formation. Autophagy 7, 1448-1461. https://doi.org/10.4161/auto.7.12.17802
  15. Mikula, M., Dzwonek, A., Hennig, E. E. and Ostrowski, J. 2005. Increased mitochondrial gene expression during L6 cell myogenesis is accelerated by insulin. Int. J. Biochem. Cell Biol. 37, 1815-1828. https://doi.org/10.1016/j.biocel.2005.02.008
  16. Ozcan, U., Cao, Q., Yilmaz, E., Lee, A. H. and Iwakoshi, N. N. 2004. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306, 457-461. https://doi.org/10.1126/science.1103160
  17. Pan, Q. R., Ren, Y. L., Liu, W. X., Hu, Y. J. and Zheng, J. S. 2015. Resveratrol prevents hepatic steatosis and endoplasmic reticulum stress and regulates the expression of genes involved in lipid metabolism, insulin resistance, and inflammation in rats. Nutr. Res. 35, 576-84. https://doi.org/10.1016/j.nutres.2015.05.006
  18. Pierre, N., Deldicque, L., Barbe, C., Naslain, D., Cani, P. D. and Francaux, M. 2013. Toll-like receptor 4 knockout mice are protected against endoplasmic reticulum stress induced by a high-fat diet. PLoS One 8, e65061. https://doi.org/10.1371/journal.pone.0065061
  19. Rodriguez, J., Gilson, H., Jamart, C., Naslain, D. and Pierre, N. 2015. Pomegranate and green tea extracts protect against ER stress induced by a high-fat diet in skeletal muscle of mice. Eur. J. Nutr. 54, 377-389.
  20. Rothe, U., Muller, G., Schwarz, P. E., Seifert, M. and Kunath, H. 2008. Evaluation of a diabetes management system based on practice guidelines, integrated care, and continuous quality management in a Federal State of Germany: a population-based approach to health care research. Diabetes Care 31, 863-868. https://doi.org/10.2337/dc07-0858
  21. Scarlatti, F., Sala, G., Somenzi, G., Signorelli, P., Sacchi, N. and Ghidoni, R. 2003. Resveratrol induces growth inhibition and apoptosis in metastatic breast cancer cells via de novo ceramide signaling. FASEB J. 17, 2339-2341. https://doi.org/10.1096/fj.03-0292fje
  22. Schefer, V. and Talan, M. I. 1996. Oxygen consumption in adult and AGED C57BL/6J mice during acute treadmill exercise of different intensity. Exp. Gerontol. 31, 387-392. https://doi.org/10.1016/0531-5565(95)02032-2
  23. Sun, X., Huo, X., Luo, T., Li, M., Yin, Y. and Jiang, Y. 2011. The anticancer flavonoid chrysin induces the unfolded protein response in hepatoma cells. J. Cell Mol. Med. 15, 2389-2398. https://doi.org/10.1111/j.1582-4934.2010.01244.x
  24. Wang, F. M., Galson, D. L., Roodman, G. D. and Ouyang, H. 2011. Resveratrol triggers the pro-apoptotic endoplasmic reticulum stress response and represses pro-survival XBP1 signaling in human multiple myeloma cells. Exp. Hematol. 39, 999-1006. https://doi.org/10.1016/j.exphem.2011.06.007
  25. Wu, J., Ruas, J. L., Estall, J. L., Rasbach, K. A. and Choi, J. H. 2011. The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC-1alpha/ ATF6alpha complex. Cell Metab. 13, 160-169. https://doi.org/10.1016/j.cmet.2011.01.003
  26. Lapidot, T., Walker M. D. and Kanner, J. 2002. Antioxidant and prooxidant effects of phenolics on pancreatic beta-cells in vitro. J. Agric Food Chem. 52, 7220-7225.
  27. Cho, H., Yun, C. W. and Park, W. K. 2004. Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives. Pharmacol. Res. 49, 37-43. https://doi.org/10.1016/S1043-6618(03)00248-2