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비만모델에서 중강도 운동에 의한 인플라마좀, 대식세포 침윤, 갈색지방 관련 바이오 마커의 개선 효과

Moderate Intensity Exercise Has More Positive Effects on The Gene Expression of Inflammasome, M1, M2 Macrophage Infiltration and Brown Adipocyte Markers Compared to High Intensity Exercise in Subcutaneous Adipose of Obese Mice Induced By High Fat Diet

  • Kim, Yong-An (Department of Sport Science, Chungnam National University) ;
  • Pitriani, Pipit (Faculty of Sports and Health Education, Indonesia University of Education) ;
  • Park, Hee-Geun (Department of Sport Science, Chungnam National University) ;
  • Lee, Wang-Lok (Department of Sport Science, Chungnam National University)
  • 투고 : 2018.11.18
  • 심사 : 2019.03.21
  • 발행 : 2019.03.30

초록

비만은 체내 과도한 지방 축적으로 인하여 지방세포 자체에서 염증성 사이토카인이 증가로 인하여 세포의 기능을 약화시킨다. 규칙적인 운동은 지방분해와 갈색지방 증가로 인해 비만의 치료방법 중 핵심 전략으로 적용되고 있다. 고강도 운동은 염증성 사이토카인과 근형질세망 스트레스 발생을 초래하여 지방대사에 부정적인 결과를 초래하는 것으로 알려져 있다. 그러나 비만모델에서 중강도 운동과 고강도 운동에 의한 인플라마좀, 대식세포 침윤, 갈색지방 관련 바이오 마커의 비교연구는 이루어진 바 없다. 따라서 이 연구의 목적은 중강도 유산소 운동과 고강도 운동을 비교하여 인플라마좀(NLRP3, ASC), 대식세포 침윤인자 M1 (CD11c, CD86), M2 (CD206), 갈색지방($PGC1{\alpha}$, BMP7, PRDM, UCP1) 관련 변인에 우선적인 효과가 있는지 비교분석하고자 하였다. 이 연구의 목적을 위해 1) 정상식이 그룹(normal diet control, NC; n=10), 2) 60% 고지방식이 그룹(high-fat diet control, HC; n=10), 3) 중강도 운동 그룹(high fat diet with moderate intensity exercise, HME; n=10), 4) 고강도 운동그룹(high fat diet with high intensity exercise, HIE; n=10)으로 나누어 실시하였다. 중강도 운동 그룹은 고지방식이 그룹과 비교하여 NLRP3, F480, CD11c, CD8의 발현이 유의하게 낮아졌다. 중강도 운동은 CD206, $PGC1{\alpha}$, BMP7, PRDM이 유의하게 증가하였다. 고강도 운동은 NLRP3, CD11c and CD86은 유의하게 감소한것으로 확인되었다. 그러나 고강도 운동은 $PGC1{\alpha}$, BMP7는 증가한다. 이러한 결과는 중강도 운동은 인플라마좀, 대식세포 M1, M2 침윤과 갈색지방 세포 관련 요인의 개선이 효과적인 것으로 나타났다.

The purpose of the study was to compare the effect of either moderate or high intensity aerobic exercise on inflammasome, M1, M2 macrophage infiltration and brown adipocyte markers in subcutaneous adipose tissue of the high fat diet-induced obese mice. The 4 weeks male C57BL/6 mice were randomly assigned to four groups: normal diet control (NC; n=10), high-fat diet control (HC; n=10), high fat diet with moderate intensity exercise (HME; n=10), or high fat diet with high intensity exercise (HIE; n=10) groups. The high fat diet was given 60% calories from fat whereas normal diet was given 18% calories from fat. The moderate intensity exercise group (HME) was set at 10m/min in the first 2 weeks, 12m/min in 3-5 weeks and 14m/min in 6-16 weeks and the high intensity exercise group (HIE) was set at 14m/min in the first 2 weeks, 17m/min in 3-5 weeks and 18m/min in 6-16 weeks. The semi quantitative reverse transcription-polymerase chain reaction (RT PCR) was used to analyze the gene expression. The moderate intensity exercise significantly reduced the expression of NLRP3, F480, CD11c and CD86. Further, the moderate intensity exercise significantly increased CD206 and $PGC1{\alpha}$, BMP7 and PRDM. The high intensity exercise significantly reduced NLRP3, CD11c and CD86. Further, the high intensity exercise significantly increased $PGC1{\alpha}$ and BMP7. In conclusion, moderate intensity exercise has more positive effects on inflammasome, M1, M2 macrophage infiltration and brown adipocyte maskers compared to high intensity exercise in high fat diet induced obese mice.

키워드

SMGHBM_2019_v29n3_303_f0001.png 이미지

Fig. 1. The change of (A) Body Weight; (B) Subcutaneous Adipose Tissue (SAT) weight of high-fat- diet-induced obese mice. Values represent means ± SEM. Different alphabet means significant difference.

SMGHBM_2019_v29n3_303_f0002.png 이미지

Fig. 2. Effect of moderate and high intensity exercise on inflammasome marker in high-fat diet induced obese mice. (A) NLRP3 Inflammasome; (B) ASC; (C) Caspase 1; (D) IL-1 β; (E) IL-18. Data represent means ± SEM. Different alphabet means significant difference.

SMGHBM_2019_v29n3_303_f0003.png 이미지

Fig. 3. The effect of moderate and high intensity exercise on macrophage marker in high-fat diet induced obese mice. (A) F480, (B) M1 macrophage marker CD11c, (C) M1 macrophage marker CD86, (D) M2 macrophage marker, CD206. Data represent means ± SEM. Different alphabet means significant difference.

SMGHBM_2019_v29n3_303_f0004.png 이미지

Fig. 4. The effect of moderate and high intensity exercise on browning marker in high-fat diet induced obese mice. (A) PGC1α, (B) BMP7, (C) UCP1, (D) PRDM16, (E) PPAR α. Data represent means±SEM. Different alphabet means significant difference.

Table 1. Reverse transcription-polymerase chain reaction primer sequences

SMGHBM_2019_v29n3_303_t0001.png 이미지

참고문헌

  1. Bai, Y. and Sun, Q. Macrophage recruitment in obese adipose tissue. 2015. Obes. Rev. 16, 127-136. https://doi.org/10.1111/obr.12242
  2. Baynard, T., Vieira-Potter, V. J., Valentine, R. J. and Woods, J. A. 2012. Exercise training effects on inflammatory gene expression in white adipose tissue of young mice. Mediators Inflamm. 28, 202-210.
  3. Bessa, A., Oliveira, V. and Espindola, F. 2016. Exercise intensity and recovery: Biomarkers of injury, inflammation, and oxidative stress. J. Strength. Con. Res. 30, 311-319. https://doi.org/10.1519/JSC.0b013e31828f1ee9
  4. Harms, M. and Seale, P. 2013. Brown and beige fat: development, function and therapeutic potential. Nat. Med. 19, 1252-1263. https://doi.org/10.1038/nm.3361
  5. Jeong, J. H., Park, H. G., Lee, Y. R. and Lee, W. L. 2015a. Moderate exercise training is more effective than resveratrol supplementation for ameliorating lipid metabolic complication in skeletal muscle of high fat diet-induced obese mice. J. Exerc. Nutr. Biochem. 19, 131-137. https://doi.org/10.5717/jenb.2015.15062211
  6. Jeong, J. H., Lee, Y. R., Park H, G. and Lee, W. L. 2015b. The effects of either resveratrol or exercise on macrophage infiltration and switching from M1 to M2 in high fat diet mice. Obesity 19, 65-72.
  7. Kawanishi, N., Yano, H., Yokogawa, Y. and Suzuki, K. Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. Exerc. Immunol. Rev. 16, 105-118.
  8. Kruger, K., Mooren, F. C. and Eder, K. 2016. Immune and Inflammatory Signaling Pathways in Exercise and Obesity. Am. J. Lifestyle Med. 10, 268-279. https://doi.org/10.1177/1559827614552986
  9. Kwon, S. M., Park, H. G., Jun, J. K. and Lee, W. L. 2014. Exercise, but not quercetin, ameliorates inflammation, mitochondrial biogenesis, and lipid metabolism in skeletal muscle after strenuous exercise by high-fat diet mice. J. Exerc. Nutr. Biochem. 18, 51-60. https://doi.org/10.5717/jenb.2014.18.1.51
  10. Linden, M. A., Pincu, Y., Martin, S. A., Woods, J. A. and Baynard, T. 2014. Moderate exercise training provides modest protection against adipose tissue inflammatory gene expression in response to high-fat feeding. Physiol. Rep. 2, 1-13.
  11. Nakhuda, A., Josse, A. R., Gburcik, V., Crossland, H., Raymond, F., Metairon, S., Good, L., Atherton, P. J., Phillips, S. M. and Timmons, J. A. 2016. Biomarkers of browning of white adipose tissue and their regulation. Am. J. Clin. Nutr. 104, 557-565. https://doi.org/10.3945/ajcn.116.132563
  12. Oliveira, A. G., Araujo, T. G., Carvalho, B. M., Guadagnini, D., Rocha, G. Z., Bagarolli, R. A., Carvalheira, J. B. C. and Saad, M. J. A. 2013. Acute exercise induces a phenotypic switch in adipose tissue macrophage polarization in diet-induced obese rats. Obesity 21, 2545-2556. https://doi.org/10.1002/oby.20402
  13. Park, H. G., Lee, Y. R., Jun, J. K. and Lee, W. L. 2014. Exercise training is more effective than resveratrol supplementation on alleviation of inflammation in peritoneal macrophages of high fat diet mice. J. Life Sci. 18, 79-87.
  14. Park, J. G., Kim, Y. A., Park, H. G. and Lee, W. L. 2018. Aerobic exercise amelirorated high fat diet induced endoplamic reticulum stress more than polyphenol supplementation in skeletal muscle of obese mice. J. Life Sci. 28, 1186-1192. https://doi.org/10.5352/JLS.2018.28.10.1186
  15. Ramos, J. S. and Dalleck, L. C. 2015. The impact of high-intensity interval training versus moderate intesity continuous triaining on vascular function: a systematic review and meta-analysis. Sports Med. 45, 679-692. https://doi.org/10.1007/s40279-015-0321-z
  16. Rocha-Rodrigues, S., Rodriguez, A., Gouveia, A. M., Goncalves, I. O., Becerril S., Ramirez, B., Beleza, J., Fruhbeck, G., Ascensao, A. and Magalhaes, J. 2016. Effects of physical exercise on myokines expression and brown adipose-like phenotype modulation in rats fed a high-fat diet. Life Sci. 165, 100-108. https://doi.org/10.1016/j.lfs.2016.09.023
  17. Sakurai, T., Ogasawara, J., Shirato, K., Izawa, T., Oh-Ishi, S., Ishibashi, Y., Radak, Z., Ohno, H. and Kizaki, T. 2017. Exercise training attenuates the dysregulated expression of adipokines and oxidative stress in white adipose tissue. Oxid. Med. Cell. Longev. 4, 25-31.
  18. Schulz, T. J. and Tseng, Y. H. 2013. Brown adipose tissue: development, metabolism and beyond. Biochem. J. 453, 167-178. https://doi.org/10.1042/BJ20130457
  19. Stanford, K. I., Middelbeek, R. J. W. and Goodyear, L. J. 2015. Exercise effects on white adipose tissue: Beiging and metabolic adaptations. Diabetes 64, 2361-2368. https://doi.org/10.2337/db15-0227
  20. Tseng, Y. H., Kokkotou, E., Schulz, T. J., Huang, T. L., Winnay, J. N., Taniguchi, C. M., Tran, T. T., Suzuki, R., Espinoza, D. O., Yamamoto, Y., Ahrens, M. J., Dudley, A. T., Norris, A. W., Kulkarni, R. N. and Kahn, C. R. 2008. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454, 1000-1004. https://doi.org/10.1038/nature07221
  21. World Health Organization, "Obesity and Overweight: Fact Sheet," 2016. [Online]. Available: http://www.who.int/mediacentre/factsheets/fs311/en/. [Accessed: 20-May-2017].
  22. Vandanmagsar, B., Youm, Y. and Ravussin, A. 2011. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 7, 15-24.