Journal of Food Hygiene and Safety (한국식품위생안전성학회지)

The Korean Society of Food Hygiene and Safety (한국식품위생안전성학회)
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The Role of Resveratrol in Lipid Metabolism: A Systematic Review of Current Basic and Translational Evidence

레스베라트롤의 지질 대사 효과에 대한 체계적 문헌 고찰

  • Choi, Seung Kug (Laboratory of Metabolic Engineering, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Moon, Hyun-Seuk (Laboratory of Metabolic Engineering, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
  • 최승국 (고려대학교 생명과학대학 생명공학부 대사공학연구실) ;
  • 문현석 (고려대학교 생명과학대학 생명공학부 대사공학연구실)
  • Received : 2016.03.02
  • Accepted : 2016.03.30
  • Published : 2016.04.30
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Abstract

Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is naturally generated in several plants in response to damage or fungal invasion. It has been shown in published studies that resveratrol has an anti-adipogenic effect. A good consensus regarding the involvement of a down-regulation of $C/EBP{\alpha}$ and $PPAR{\gamma}$ in this effect has been reached. In addition, different metabolic pathways involved in triacylglycerol metabolism in white adipose tissue have been shown to be regulated by resveratrol. Concerning lipolysis, though this compound in itself seems to be unable to cause lipolysis, it increases lipid mobilization stimulated by ${\beta}-adrenergic$ agents. The increase in brown adipose tissue thermogenesis, and accordingly the associated energy dissipation, can attribute to accounting for the body-fat reducing effect of resveratrol. Besides its effects on adipose tissue, resveratrol can also acts on other organs and tissues. Therefore, it increases mitochondrial biogenesis and accordingly fatty acid oxidation in skeletal muscle and liver. This effect can also attribute to the body-fat reducing effect of this molecule. The present review purposes to collect the evidence concerning the potential mechanisms of action which underlie the anti-obesity effects of resveratrol, acquired either in cultured cells lines and animal models.

본 총설에서는 비-플라보노이드 폴리페놀인 레스베라트롤이 간, 골격근 및 지방조직에서 지질대사에 관계된 다양한 신호전달체계를 조절하여 지질 대사 효과를 유발시키는 과정에 관해 고찰하였다. 구체적으로 in vitro 연구에서 레스베라트롤은 지방생성을 줄여주고 apoptosis를 증가시켜 지방세포의 발달과정에 기인하며, 지방세포의 분화에 있어 중요한 전사인자인 $C/EBP{\beta}$, $C/EBP{\alpha}$, SREBP1c 및 $PPAR{\gamma}$의 활성을 감소시켜 항 비만 효과를 유발하는 효과가 있다는 것이 많은 논문들을 통해 증명되었다(Fig. 2). 또한, in vivo 연구에서 레스베라트롤은 지방 축적 과정을 억제하고 지질 분해 및 산화 경로를 자극하여 체지방 증가율을 감소시킨다는 것이 증명되었다. 최근 다양한 연구의 결과물(Table 2)들은 레스베라트롤이 지방생성, 지방분해, 열발생 및 지방산 산화에 관여하며 또한, 백색 지방을 갈색 지방으로 변화시키는 능력이 있다는 것을 증명하였다. 흥미롭게도 레스베라트롤은 비만뿐만이 아닌 심장발작 및 뇌졸중과 같은 다양한 대사질환을 예방하는데 도움이 되고, 결장암 및 간암 세포의 성장을 억제하는 효능이 있다는 사실이 밝혀지기도 하였다. 하지만 인간에 대한 레스베라트롤의 명확한 메커니즘을 알지 못하고 인간에게 나타나는 부작용에 관한 연구가 없기 때문에, 안전성을 확보하기 위해서는 다양한 실험모델을 이용한 레스베라트롤의 단기간 및 장기간에 대한 깊은 연구가 요구된다.

Keywords

References

  1. Leiherer, A. Mündlein, A. Drexel, H.: Phytochemicals and their impact on adipose tissue inflammation and diabetes. Vascul. Pharmacol. 58, 3-20 (2013). https://doi.org/10.1016/j.vph.2012.09.002
  2. Burns, J. Yokota, T. Ashihara, H. Lean, M.E. Crozier, A. Plant foods and herbal sources of resveratrol.: J. Agric. Food Chem., 50, 3337-3340 (2002). https://doi.org/10.1021/jf0112973
  3. Borriello, A. Cucciolla, V. Della Ragione, F. Galletti, P.: Dietary polyphenols: Focus on resveratrol, a promising agent in the prevention of cardiovascular diseases and control of glucose homeostasis. Nutr. Metab. Cardiovasc. Dis., 20, 618-625 (2010). https://doi.org/10.1016/j.numecd.2010.07.004
  4. Wenzel, E. Somoza, V.: Metabolism and bioavailability of trans-resveratrol. Mol. Nutr. Food Res., 49, 472-481 (2005). https://doi.org/10.1002/mnfr.200500010
  5. Walle, T. Hsieh, F. DeLegge, M.H. Oatis, J.E. Walle, U.K.: High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Dispos., 32, 1377-1382 (2004). https://doi.org/10.1124/dmd.104.000885
  6. Baur, J.A. Pearson, K.J. Price, N.L. Jamieson, H.A. Lerin, C. Kalra, A. Prabhu, V.V. Allard, J.S. Lopez-Lluch, G. Lewis, K.: Resveratrol improves health and survival of mice on a high-calorie diet. Nature, 444, 337-342 (2006). https://doi.org/10.1038/nature05354
  7. Espín, J.C. García-Conesa, M.T. Tomás-Barberán, F.A.: Nutraceuticals: Facts and fiction. Phytochemistry, 68, 2986-3008 (2007). https://doi.org/10.1016/j.phytochem.2007.09.014
  8. Szkudelska, K. Szkudelski, T.: Resveratrol, obesity and diabetes. Eur. J. Pharmacol., 635, 1-8 (2010). https://doi.org/10.1016/j.ejphar.2010.02.054
  9. Szkudelski, T. Szkudelska, K.: Anti-diabetic effects of resveratrol. Ann. N. Y. Acad. Sci., 1215, 34-39 (2011). https://doi.org/10.1111/j.1749-6632.2010.05844.x
  10. Timmers, S. Konings, E. Bilet, L. Houtkooper, R.H. van de Weijer, T. Goossens, G.H. Hoeks, J. van der Krieken, S. Ryu, D. Kersten.: Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab., 14, 612-622 (2011). https://doi.org/10.1016/j.cmet.2011.10.002
  11. Meydani, M. Hasan, S.T.: Dietary polyphenols and obesity. Nutrients, 2, 737-751 (2010). https://doi.org/10.3390/nu2070737
  12. Catalan, V. Gomez-Ambrosi, J. Rodriguez, A. Frühbeck, G.: Role of extracellular matrix remodelling in adipose tissue pathophysiology: Relevance in the development of obesity. Histol. Histopathol., 27, 1515-1522 (2012).
  13. Rosen, E.D. MacDougald, O.A.: Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol., 7, 885-896 (2006). https://doi.org/10.1038/nrm2066
  14. Gregoire, F.M. Smas, C.M. Sul, H.S.: Understanding adipocyte differentiation. Physiol. Rev., 78, 783-809 (1998). https://doi.org/10.1152/physrev.1998.78.3.783
  15. Farmer, S.R.: Transcriptional control of adipocyte formation. Cell Metab., 4, 263-273 (2006). https://doi.org/10.1016/j.cmet.2006.07.001
  16. Kwon, J.Y. Seo, S.G. Yue, S Cheng, J.X. Lee, K.W. Kim, K.H.: An inhibitory effect of resveratrol in the mitotic clonal expansion and insulin signaling pathway in the early phase of adipogenesis. Nutr. Res., 32, 607-616 (2012). https://doi.org/10.1016/j.nutres.2012.06.014
  17. Chen, S. Li, Z. Li, W. Shan, Z. Zhu, W. Resveratrol inhibits cell differentiation in 3T3-L1 adipocytes via activation of AMPK. Can. J. Physiol. Pharmacol., 89, 793-799 (2011)
  18. Rayalam, S. Yang, J.Y. Ambati, S. Della-Fera, M.A. Baile, C.A.: Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother. Res., 22, 1367-1371 (2008). https://doi.org/10.1002/ptr.2503
  19. Lasa, A. Churruca, I. Eseberri, I. Andrés-Lacueva, C. Portillo, M.P.: Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes. Mol. Nutr. Food Res., 56, 1559-1568 (2012). https://doi.org/10.1002/mnfr.201100772
  20. Carpéné, C. Gómez-Zorita, S. Deleruyelle, S. Carpéné, M.A.: Novel strategies for preventing diabetes and obesity complications with natural polyphenols. Curr. Med. Chem., 22, 150-164 (2014). https://doi.org/10.2174/0929867321666140815124052
  21. Fisher-Posovszky, P. Kukulus, V. Tews, D. Unterkircher, T. Debatin, K.M. Fulda, S. Wabitsch, M.: Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. Am. J. Clin. Nutr., 92, 5-15 (2010). https://doi.org/10.3945/ajcn.2009.28435
  22. Thornberry N.A, Lazebnik, Y : Caspases: Enemies within. Scienc., 281, 1312-1316 (1998). https://doi.org/10.1126/science.281.5381.1312
  23. Ashkenazi A., Salvesen, G.: Regulated Cell Death: Signaling and Mechanisms. Ann. Rev. Cell Dev. Biol., 30, 337-356 (2014). https://doi.org/10.1146/annurev-cellbio-100913-013226
  24. Salvesen, G.S. Ashkenazi, A. Snapshot : Caspases. Cell., 147, 476-476.e1, doi:10.1016/j.cell.2011.09.030 (2011).
  25. Adams, J.M. Cory, S.: The Bcl-2 protein family: Arbiters of cell survival. Science., 281, 1322-1326 (1998). https://doi.org/10.1126/science.281.5381.1322
  26. Yang, J.Y. Della-Fera, M.A. Rayalam, S. Ambati, S. Hartzell, D.L. Park, H.J. Baile, C.A.: Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Sci., 82, 1032-1039 (2008). https://doi.org/10.1016/j.lfs.2008.03.003
  27. Rayalam, S. Della-Fera, M.A. Yang, J.Y. Park, H.J. Ambati, S. Baile, C.A.: Resveratrol potentiates genistein's antiadipogenic and proapoptotic effects in 3T3-L1 adipocytes. J. Nutr., 137, 2668-2673 (2007). https://doi.org/10.1093/jn/137.12.2668
  28. Park, H.J. Yang, J.Y. Ambati, S. Della-Fera, M.A. Hausman, D.B. Rayalam, S. Baile, C.A.: Combined effects of genistein, quercetin, and resveratrol in human and 3T3-L1 adipocytes. J. Med Food., 11, 773-783 (2008). https://doi.org/10.1089/jmf.2008.0077
  29. Chen, S. Xiao, X. Feng, X. Li, W. Zhou, N., Zheng, L. Sun, Y. Zhang, Z. Zhu, W.: Resveratrol induces Sirt1-dependent apoptosis in 3T3-L1 preadipocytes by activating AMPK and suppressing AKT activity and survivin expression. J. Nutr. Biochem., 23, 1100-1112 (2012). https://doi.org/10.1016/j.jnutbio.2011.06.003
  30. Pang, W.J. Xiong, Y. Zhang, Z. Wei, N. Chen, N. Yang, G.S.: Lentivirus-mediated Sirt1 shRNA and resveratrol independently induce porcine preadipocyte apoptosis by canonical apoptotic pathway. Mol. Biol. Rep., 40, 129-139 (2013). https://doi.org/10.1007/s11033-012-2041-x
  31. Zimmermann, R. Strauss, J.G. Haemmerle, G. Schoiswohl, G. Birner-Gruenberger, R. Riederer, M. Lass, A. Neuberger, G. Eisenhaber, F. Hermetter, A.: Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science, 306, 1383-1386 (2004). https://doi.org/10.1126/science.1100747
  32. Lafontan, M. Langin, D.: Lipolysis and lipid mobilization in human adipose tissue. Prog. Lipid Res., 48, 275-297 (2009). https://doi.org/10.1016/j.plipres.2009.05.001
  33. Szkudelska, K. Nogowski, L. Szkudelski, T.: Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and the antilipolytic action of insulin in isolated rat adipocytes. J. Steroid. Biochem. Mol. Biol., 113, 17-24 (2009). https://doi.org/10.1016/j.jsbmb.2008.11.001
  34. Picard, F. Guarente, L.: Molecular links between aging and adipose tissue. Int. J. Obes. (Lond.), 29, S36-S39 (2005). https://doi.org/10.1038/sj.ijo.0802912
  35. Picard, F. Kurtev, M. Chung, N. Topark-Ngarm, A. Senawong, T. Machado de Oliveira, R. Leid, M. McBurney, M.W. Guarente, L.: Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature, 429, 771-776 (2004). https://doi.org/10.1038/nature02583
  36. Shan, T. Ren, Y. Wang, Y.: Sirtuin 1 affects the transcriptional expression of adipose triglyceride lipase in porcine adipocytes. J. Anim. Sci., 91, 1247-1254 (2013). https://doi.org/10.2527/jas.2011-5030
  37. Lasa, A. Schweiger, M. Kotzbeck, P. Churruca, I. Simón, E. Zechner, R. Portillo, M.P.: Resveratrol regulates lipolysis via adipose triglyceride lipase. J. Nutr. Biochem., 23, 379-384 (2012). https://doi.org/10.1016/j.jnutbio.2010.12.014
  38. Rosenow, A. Noben, J.P. Jocken, J. Kallendrusch, S. Fischer-Posovszky, P. Mariman, E.C.: Renes, J. Resveratrol-induced changes of the human adipocyte secretion profile. J. Proteome Res., 11, 4733-4743 (2012). https://doi.org/10.1021/pr300539b
  39. Pedersen, S.B. Olholm, J. Paulsen, S.K. Bennetzen, M.F. Richelsen, B.: Low Sirt1 expression, which is upregulated by fasting, in human adipose tissue from obese women. Int. J. Obes. (Lond.), 32, 1250-1255 (2008). https://doi.org/10.1038/ijo.2008.78
  40. Gomez-Zorita, S. Treguer, K. Mercader, J. Carpene, C.: Resveratrol directly affects in vitro lipolysis and glucose transport in human fat cells. J. Physiol Biochem., 69, 585-593 (2013). https://doi.org/10.1007/s13105-012-0229-0
  41. Alberdi, G. Rodríguez, V.M. Miranda, J. Macarulla, M.T. Arias, N. Andrés-Lacueva, C. Portillo, M.P.: Changes in white adipose tissue metabolism induced by resveratrol in rats. Nutr. Metab. (Lond.)., 8, 29-35 (2011). https://doi.org/10.1186/1743-7075-8-29
  42. Gomez-Zorita, S. Fernandez-Quintela, A. Lasa, A. Hijona, E. Bujanda, L. Portillo, M.P.: Effects of resveratrol on obesity- related inflammation markers in adipose tissue of genetically obese rats. Nutrition., 29, 1374-1380 (2013). https://doi.org/10.1016/j.nut.2013.04.014
  43. Lowell, B.B. Spiegelman, B.M.: Towards a molecular understanding of adaptive thermogenesis. Nature, 404, 652-660 (2000). https://doi.org/10.1038/35007527
  44. Ricquier, D. Casteilla, L.: Bouillaud, F. Molecular studies of the uncoupling protein. FASEB J., 5, 2237-2242 (1991). https://doi.org/10.1096/fasebj.5.9.1860614
  45. Alberdi, G. Rodríguez, V.M. Miranda, J. Macarulla, M.T. Churruca, I. Portillo, M.P.: Thermogenesis is involved in the body-fat lowering effects of resveratrol in rats. Food Chem., 141, 1530-1535 (2013). https://doi.org/10.1016/j.foodchem.2013.03.085
  46. Barger, J.L. Kayo, T. Vann, J.M. Arias, E.B. Wang, J. Hacker, T.A. Wang, Y. Raederstorff, D. Morrow, J.D. Leeuwenburgh, C.: A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One, 3, e2264 (2008). https://doi.org/10.1371/journal.pone.0002264
  47. Lagouge, M. Argmann, C. Gerhart-Hines, Z. Meziane, H. Lerin, C. Daussin, F. Messadeq, N. Milne, J. Lambert, P. Elliott, P.: Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell, 127, 1109-1122 (2006). https://doi.org/10.1016/j.cell.2006.11.013
  48. Oliveira, J.M. Montes, A.C. Bohnen, J. Freitas, K.M. Paz, M.T. Sena, A.L. Batista de Paula, A.M. Coimbra, C.C. Sousa, S.H.: Resveratrol increases brown adipose tissue thermogenesis markers by increasing SIRT1 and energy expenditure and decreasing fat accumulation in adipose tissue of mice fed a standard diet. Eur. J. Nutr., 53, 1503-1510 (2014). https://doi.org/10.1007/s00394-014-0655-6
  49. Galgani, J. Ravussin, E.: Energy metabolism, fuel selection and body weight regulation. Int. J. Obes. (Lond.), 32, S109-S119 (2008). https://doi.org/10.1038/ijo.2008.246
  50. Isken, F. Klaus, S. Petzke, K.J. Loddenkemper, C. Pfeiffer, A.F. Weickert, M.O.: Impairment of fat oxidation under high- vs. low-glycemic index diet occurs before the development of an obese phenotype. Am. J. Physiol. Endocrinol. Metab., 298, E287-E295 (2010). https://doi.org/10.1152/ajpendo.00515.2009
  51. Eaton, S. Bartlett, K. Pourfarzam, M.: Mammalian mitochondrial beta-oxidation. Biochem. J., 320, 345-357 (1996). https://doi.org/10.1042/bj3200345
  52. Kerner, J. Hoppel, C.: Fatty acid import into mitochondria. Biochim. Biophys. Acta, 1486, 1-17 (2000). https://doi.org/10.1016/S1388-1981(00)00044-5
  53. Duplus, E. Forest, C.: Is there a single mechanism for fatty acid regulation of gene transcription? Biochem. Pharmacol., 64, 893-901 (2002). https://doi.org/10.1016/S0006-2952(02)01157-7
  54. Alberdi, G. Rodríguez, V.M. Macarulla, M.T. Miranda, J. Churruca, I. Portillo, M.P.: Hepatic lipid metabolic pathways modified by resveratrol in rats fed an obesogenic diet. Nutrition, 29, 562-567 (2013). https://doi.org/10.1016/j.nut.2012.09.011
  55. Ahn, J. Cho, I. Kim, S. Kwon, D. Ha, T.: Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet. J. Hepatol., 49, 1019-1028 (2008). https://doi.org/10.1016/j.jhep.2008.08.012