Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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The Effects of Either Chrysin or Moderate Exercise on Inflammasome and Thermogenic Markers in High Fat Fed Mice

고지방식이 동물의 간 조직에서 크리신 투여 또는 중강도 운동이 Inflammasome과 열 발생 유전자발현에 미치는 효과

  • Lee, Young-Ran (Center for Sport Science in Jeonbuk) ;
  • Park, Hee-Geun (Department of Sport Science, College of Natural Science, Chungnam National University) ;
  • Lee, Wang-Lok (Department of Sport Science, College of Natural Science, Chungnam National University)
  • Received : 2019.03.25
  • Accepted : 2019.04.25
  • Published : 2019.05.30
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Abstract

The purpose of this study was to investigate the effects of either chrysin or exercise on the inflammasome and thermogenic markers in the livers of high-fat fed mice. C57BL/6 mice were randomly assigned to four groups: normal diet control (NC; n=5), high-fat diet control (HC; n=5), high-fat diet with chrysin (Hch; n=5), and high-fat diet with moderate exercise (HME; n=5). The mice were fed a high-fat diet (60% of calories from fat) or normal diet (18% of calories from fat). Chrysin was supplemented orally as 50mg/kg/day dissolved in a 0.1ml solution of dimethyl sulfoxide. The exercised mice ran on a treadmill at 12-20 m/min for 30-60 min/day, 5 times/week, for 16 weeks. After the intervention, the epididymal fat and liver weights were significantly decreased in the HME group compared with HC and Hch groups. The adipocyte size was effectively decreased in the Hch and HME groups compared with the HC group. The inflammasome markers NLRP3, $IL-1{\beta}$, and caspase1 were significantly decreased in the Hch and HME groups compared with the HC group. The thermogenic markers $PGC-1{\alpha}$ and BMP7 were significantly lower in the HC than in the NC group. However, the HME group showed an increase in the thermogenic markers. In conclusion, chrysin and moderate exercise have positive effects on obese metabolic complications induced by high-fat diets by reducing inflammasome genes. However, chrysin supplementation had no effect on thermogenic gene expression. Moderate exercise would therefore seem to be more effective in controlling obesity-induced metabolic deregulation.

본 연구 목적은 고지방식이 동물의 간 조직에서 크리신 투여 또는 중강도운동이 Inflammasome과 thermogenesis 유전자 발현의 차이를 규명하고자 시도되었다. 본 연구를 위해 정상식이군, 고지방식이군, 고지방식이+크리신 투여군, 고지방식이+중강도 운동군으로 분류한 후, 크리신 투여군은 16주간 50 mg/kg 농도로 투여하였으며, 운동군은 최대산소섭취량의 60-75%의 중강도 운동으로 실시되었다. 연구결과 크리신 그리고 중강도운동군은 지방조직, 간조직 무게 그리고 지방세포 크기가 고지방식이 군과 비교해 유의하게 감소하였다. Inflammasome 유전자 변화는 크리신 투여군 그리고 중강도 운동군에서 NLRP3. ASC, Casepase1 mRNA 발현이 고지방식이 군과 비교해 유의하게 감소하였다. 열발생마커로 알려진 PGC-1a, BMP7 mRNA 발현은 중강도 운동군에서만 고지방식 이군과 비교해 유의하게 증가했다. 결론적으로 중강도 운동은 고지방식이 동물에서 지방무게, Inflammasome, 그리고 열발생 유전자들의 발현을 비만을 억제하는데 긍정적인 영향을 미치는 것으로 보여진다. 하지만 크리신 투여는 열발생 유전자 발현에는 유의한 차이를 나타내지 못하였다. 향후 연구에서는 크리신의 비만억제 효과를 규명하기 위해 투여농도 기간을 고려한 다양한 연구가 진행되어야 할 것이다.

Keywords

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Fig. 1. The change of (A)epididymal fat ;(B) liver weight of high-fat fed mice.

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Fig. 2. The change of adipocyte size of high-fat fed mice.

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Fig 3. The change of inflammasome markers of high-fat fed mice.

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Fig. 4. The change of thermogenic markers in liver of high-fat fed mice.

Table 1. Primer sequences used for RT-PCR

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References

  1. Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, N. L., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., Pistell, P. J., Poosala, S., Becker, K. G., Boss, O., Gwinn, D., Wang, M., Ramaswamy, S., Fishbein, K. W., Spencer, R. G., Lakatta, E. G., Le Couteur, D., Shaw, R. J., Navas, P., Puigserver, P., Ingram, D. K., Cabo, R. and Sinclair, D. A. 2006. Resveratrol improves health and survival of mice on high-calorie diet. Nature 444, 337-342. https://doi.org/10.1038/nature05354
  2. Cho, H., Yun, C. W., Park, W. K., Kong, J. Y., Kim, K. S., Park, Y., Leem, S. and Kim, B. 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
  3. Duarte, J., Jimenez, R., Villar, I. C., Perez-Vizcaino, F., Jimenez, J. and Tamargo, J. 2001. Vasorelaxant effects of the bioflavonoid chrysin in isolated rat aorta. Planta Med. 67, 567-569. https://doi.org/10.1055/s-2001-16492
  4. Gleeson, M., Bishop, N. C., Stensel, D. J., Lindley, M. R., Mastana, S. S. and Nimmo, M. A. 2011. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease Nat. Rev. Immunol. 5, 607-615.
  5. Haneklaus, M. and O'Neill, L. A. J. 2015. NLRP3 at the interface of metabolism and inflammation. Immunol. Rev. 265, 53-62. https://doi.org/10.1111/imr.12285
  6. Haram, P. M., Kemi, O. J., Lee, S. J., Bendheim. M. O., Al-Share, Q. Y., Waldum, H. L, Gilligan, L. J., Koch, L. G., Britton, S. L., Najjar, S. M. and Wisloff, U. 2009. Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity. Cardiovasc. Res. 81, 723-732. https://doi.org/10.1093/cvr/cvn332
  7. Hondares, E., Rosell, M., Diaz-Delfin, J., Olmos, Y., Monsalve, M., Iglesias, R., Villarroya, F. and Giralt, M. 2011. Peroxisome proliferator activated receptor-alpha (PPAR ${\alpha}$) induces PPAR ${\gamma}$-coactivator 1 ${\alpha}$ (PGC-1 ${\alpha}$) gene expression and contributes to thermogenic activation of brown fat: involvement of PRDM16. J. Biol. Chem. 286, 43112-43122. https://doi.org/10.1074/jbc.M111.252775
  8. Izuta, H., Shimazama, M., Tazawa, S., Araki, Y., Mishima, S. and Hara, H. 2008. Protective effects of Chinese propolis and its component, chrysin, against neuronal cell death via inhibition of mitochondrial apoptosis pathway in SH-SY5Y cells. J. Agric. Food. Chem. 56. 8944-8953. https://doi.org/10.1021/jf8014206
  9. Jeong, J. H., Lee, Y. R., Park, H. G. and Lee, W. L. 2015. 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
  10. Juan Jose, R. E., Johann, S. R., Sara, G. J., Rafael, V. M., Gabriela, A. V., Angelica N. R. O., German, B. F. and Samuel, E. S. 2017. Chrysin induces antidiabetic, antidyslipidemic and anti-inflammatory effects in athymic nude diabetic mice. Molecules 23, pii:E67.
  11. Jun, J. K., Lee, W. L., Park, H. G., Lee, S. K., Jeong, S. H. and Lee, Y. R. 2014. Moderate intensity exercise inhibits macrophage infiltration and attenuates adipocyte inflammation in ovariectomized rats. J. Exerc. Nutr. Biochem. 18, 119-127. https://doi.org/10.5717/jenb.2014.18.1.119
  12. Kawanishi, N., Yano, H., Yokogawa, Y. and Suzuki, K. 2010. 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. Exer. Immunol. Rev. 16, 105-118.
  13. King, G. A., Fitzhugh, E. C., Bassett, Jr. D. R., McLaughlin, J. E., Strath, S. J., Swartz, A. M. and Thompson, D. L. 2001. Relationship of leisure-time physical activity and occupational activity to the prevalence of obesity. Int. J. Obes. Relat. Metab. Disord. 25, 606-612. https://doi.org/10.1038/sj.ijo.0801583
  14. Lagouge, M., Argmann, C., Grhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., Geny, B., Laakso, M., Puigserver, P. and Auwerx, J. 2006. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1a. Cell 127, 1-14. https://doi.org/10.1016/j.cell.2006.09.022
  15. Lee, Y. R., Jeong, S. H., Park, H. G., Jeong. J. H. and Lee, W. L. 2013. The effects of either resveratrol supplementation or aerobic exercise training combined with a low fat diet on the molecules of adipogenesis and adipocyte inflammation in high fat diet induced obese mice. J. Exerc. Nutr. Biochem. 17, 15-20.
  16. Lee, Y. R., Pipit, P., Park, H. G. and Lee, W. L. Resveratrol ameliorates high-fat-induced metabolic complications by changing the expression of inflammasome markers and macrophage M1 and M2 markers in obese mice. J. Life. Sci. 27, 1462-1469. https://doi.org/10.5352/JLS.2017.27.12.1462
  17. Li, R. X., Yiu, W. H. and Tang, S. C. 2015. Role of bone morphogenetic protein-7 in renal fibrosis. Front. Physiol. 6, 114. https://doi.org/10.3389/fphys.2015.00114
  18. Mardare, C., Kruger, K., Liebisch, G., Seimetz, M., Couturier, A., Ringseis, R., Wilhelm, J., Weissmann, N., Eder, K. and Mooren, F. C. 2016. Endurance and resistance training affect high fat diet-induced increase of ceramides, inflammasome expression, and systemic inflammation in mice. J. Diabetes Res. 2016, 4536470.
  19. McCarthy, E. M. and Rinella, M. E. 2012. The role of diet and nutrient composition in nonalcoholic fatty liver disease. J. Acad. Nutr. Diet. 112, 401-409. https://doi.org/10.1016/j.jada.2011.10.007
  20. Promrat, K, Kleiner, D. E., Niemeier, H. M., Jackvony, E., Kearns, M., Wands, J. R., Fava, J. L. and Wing, R. R. 2010. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51, 121-129. https://doi.org/10.1002/hep.23276
  21. Ringseis, R., Eder, K., Mooren, F. C. and Kruger, K. 2015. Metabolic signals and innate immune activation in obesity and exercise. Exerc. Immunol. Rev. 21, 58-68.
  22. Rocha, K. K., Souza, G. A., Ebaid, G. X., Seiva, F. R., Cataneo, A. C. and Novelli, E. L. 2009. Resveratrol toxicity: effects on risk factors for atherosclerosis and hepatic oxidative stress in standard and high-fat diets. Food. Chem. Toxicol. 47, 1362-1367. https://doi.org/10.1016/j.fct.2009.03.010
  23. 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
  24. Schroder, K. T. and Schopp, J. 2010. The inflammasomes. Cell 140, 821-832 https://doi.org/10.1016/j.cell.2010.01.040
  25. Schroder, K. Zhou, R. T. and Schopp, J. 2010. The NLRP3 inflammasome: a sensor for metabolic danger? Science 327, 296-300. https://doi.org/10.1126/science.1184003
  26. Skeldon, A. M., Faraj, M. and Saleh, M. 2014. Caspases and inflammasomes in metabolic inflammation. Immunol. Cell Biol. 92, 304-313. https://doi.org/10.1038/icb.2014.5
  27. Sobocanec, S., Sverko, V., Balog, T., Saric, A., Rusak, G., Likic, S., Kusic, B., Katalinic, V., Radic, S. and Marotti, T. 2006. Oxidant/antioxidant properties of Croatian native propolis. J. Agric. Food. Chem. 54, 8018-8026. https://doi.org/10.1021/jf0612023
  28. Sugimoto, H., Yang, C., LeBleu, V. S., Soubasakos, M. A., Giraldo, M., Zeisberg, M. and Kalluri, R. 2007. BMP-7 functions as a novel hormone to facilitate liver regeneration. FASEB. J. 21, 256-264. https://doi.org/10.1096/fj.06-6837com
  29. Unger, R. H. and Orci, L. 2000. Lipotoxic diseases of nonadipose tissues in obesity. Int. J. Obes. Relat. Metab. Disord. 24, S28-32. https://doi.org/10.1038/sj.ijo.0801498
  30. Vandanmagsar, B., Youm, Y. H., Ravussin, A., Galgani, J. E., Stadler, K., Mynatt, R. L., Ravussin, E., Stephens, J. M. and Dixit, V. D. 2011. The NALP3/NLRP3 inflammasome instigates obesity-induced autoinflammation and insulin resistance. Nat. Med. 17, 179-188. https://doi.org/10.1038/nm.2279
  31. Williams, C. A., Harborne, J. B., Newman, M., Greenham, J. and Eagles, J. 1997. Chrysin and other leaf exudate flavonoids in the genus Pelargonium. Phytochemistry 46, 1349-1353. https://doi.org/10.1016/S0031-9422(97)00514-1
  32. Wree, A., Eguchi, A., McGeough, M. D., Pena, C. A., Johnson, C. D., Canbay, A. Hoffman, H. M. and Feldstein, A. E. 2014. NLRP3 inflammasome activation results in epaticyte pyroptosis, liver inflammation and fibrosis. Hepatology 59, 898-910. https://doi.org/10.1002/hep.26592