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Enzymatically Modified Isoquercitrin Attenuates High-Fat Diet-Induced Obesity

효소 처리된 Isoquercitrin이 고지방식이에 의해 비만이 유도된 마우스의 체중감소에 미치는 영향

  • Min, Yeojin (Department of Food and Nutrition, Yonsei University) ;
  • Park, Taesun (Department of Food and Nutrition, Yonsei University)
  • 민여진 (연세대학교 생활과학대학 식품영양학과) ;
  • 박태선 (연세대학교 생활과학대학 식품영양학과)
  • Received : 2015.12.07
  • Accepted : 2015.12.22
  • Published : 2016.04.30

Abstract

Enzymatically modified isoquercitrin (EMIQ) is a mixture of quercetin glycodsides consisting of isoquercitrin and its ${\alpha}-glucosylated$ derivatives containing one to seven additional linear glucose moieties. The aim of this study was to assess whether or not EMIQ attenuates high-fat diet (HFD)-induced body weight gain and changes in plasma indices of obesity in mice. Male C57BL/6N mice were fed chow diet, HFD, and HFD containing 1.2% EMIQ for 10 weeks. EMIQ significantly (P<0.05) reduced body weight gain (-21%), total visceral fat-pad weights (-31%), and plasma levels of triglycerides (-17%), total cholesterol (-19%), and free fatty acids (-26%) in HFD-fed mice. EMIQ significantly increased protein kinase A (PKA) expression in the epididymal adipose tissue of HFD-fed mice. Expression of adipogenesis-related genes significantly decreased, whereas expression of fatty acid oxidation-related and thermogenesis-related genes increased in epididymal adipose tissue of EMIQ-fed mice compared with HFD-fed mice. These results suggest that the protective effects of EMIQ against HFD-induced adiposity in mice appear to be associated with PKA-mediated signaling cascades involved in adipogenesis, fatty acid oxidation, and thermogenesis in adipose tissue.

References

  1. Chua SJ, Leibel RL. 1997. Obesity genes: molecular and metabolic mechanisms. Diabetes Rev 5: 2-7.
  2. Fajas L, Fruchart JC, Auwerx J. 1998. Transcriptional control of adipogenesis. Curr Opin Cell Biol 10: 165-173. https://doi.org/10.1016/S0955-0674(98)80138-5
  3. Cannon B, Nedergaard J. 2004. Brown adipose tissue: function and physiological significance. Physiol Rev 84: 277-359. https://doi.org/10.1152/physrev.00015.2003
  4. Fritz IB, Yue KT. 1963. Long-chain carnitine acyltransferase and the role of acylcarnitine derivatives in the catalytic increase of fatty acid oxidation induced by carnitine. J Lipid Res 4: 279-288.
  5. Akiyama T, Washino T, Yamada T, Koda T, Maitani T. 2000. Constituents of enzymatically modified isoquercitrin and enzymatically modified rutin (extract). J Food Hyg Soc Japan 41: 54-60. https://doi.org/10.3358/shokueishi.41.54
  6. Moriwaki M. 2002. Availability of flavonoid as antioxidants for beverages. Soft Drinks Technol 137: 57-79.
  7. Emura K, Yokomizo A, Toyoshi T, Moriwaki M. 2007. Effect of enzymatically modified isoquercitrin in spontaneously hypertensive rats. J Nutr Sci Vitaminol 53: 68-74. https://doi.org/10.3177/jnsv.53.68
  8. Makino T, Kanemaru M, Okuyama S, Shimizu R, Tanaka H, Mizukami H. 2013. Anti-allergic effects of enzymatically modified isoquercitrin (${\alpha}$-oligoglucosyl quercetin 3-O-glucoside), quercetin 3-O-glucoside, ${\alpha}$-oligoglucosyl rutin, and quercetin, when administered orally to mice. J Nat Med 67:881-886. https://doi.org/10.1007/s11418-013-0760-5
  9. Morita R, Shimamoto K, Ishii Y, Kuwata K, Ogawa B, Imaoka M, Hayashi S, Suzuki K, Shibutani M, Mitsumori K. 2011. Suppressive effect of enzymatically modified isoquercitrin on phenobarbital-induced liver tumor promotion in rats. Arch Toxicol 85: 1475-1484. https://doi.org/10.1007/s00204-011-0696-z
  10. Tateishi N, Egawa K, Kanzaki N, Kitagawa Y, Shibata H, Kiso Y, Enomoto S, Fukuda D, Nagai R, Sata M. 2009. Effects of quercetin glucosides on diet-induced obesity in mice: the lipolytic activity of quercetin. Jpn Pharmacol Ther 37: 123-131.
  11. Yoshimura M, Maeda A, Takehara I, Abe K, Ohta H, Kiso Y, Fukuhara I, Sakane N. 2008. Body fat reducing effect and safety of the beverage containing polyphenols derived from Japanese pagoda tree (enzymatically modified isoquercitrin) in overweight and obese subjects. Jpn Pharmacol Ther 36: 919-930.
  12. FDA. 2007. GRAS Notification for alpha-glycosyl isoquercitrin.
  13. Reagan-Shaw S, Nihal M, Ahmad N. 2007. Dose translation from animal to human studies revisited. FASEB J 22: 659-661. https://doi.org/10.1096/fj.07-9574LSF
  14. Makino T, Shimizu R, Kanemaru M, Suzuki Y, Moriwaki M, Mizukami H. 2009. Enzymatically modified isoquercitrin, ${\alpha}$-oligoglucosyl quercetin 3-O-glucoside, is absorbed more easily than other quercetin glycosides or aglycone after oral administration in rats. Biol Pharm Bull 32: 2034-2040. https://doi.org/10.1248/bpb.32.2034
  15. Day AJ, Cañada FJ, Díaz JC, Kroon PA, Mclauchlan R, Faulds CB, Plumb GW, Morgan MRA, Williamson G. 2000. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett 468: 166-170. https://doi.org/10.1016/S0014-5793(00)01211-4
  16. Arts ICW, Sesink ALA, Faassen-Peters M, Hollman PCH. 2004. The type of sugar moiety is a major determinant of the small intestinal uptake and subsequent biliary excretion of dietary quercetin glycosides. Br J Nutr 91: 841-847. https://doi.org/10.1079/BJN20041123
  17. Lesser S, Cermak R, Wolffram S. 2004. Bioavailability of quercetin in pigs is influenced by the dietary fat content. J Nutr 134: 1508-1511. https://doi.org/10.1093/jn/134.6.1508
  18. Enns LC, Ladiges W. 2010. Protein kinase A signaling as an anti-aging target. Ageing Res Rev 9: 269-272. https://doi.org/10.1016/j.arr.2010.02.004
  19. Lowell BB, Spiegelman BM. 2000. Towards a molecular understanding of adaptive thermogenesis. Nature 404: 652-660. https://doi.org/10.1038/35007527
  20. Fernandez-Veledo S, Vazquez-Carballo A, Vila-Bedmar R, Ceperuelo-Mallafre V, Vendrell J. 2013. Role of energyand nutrient-sensing kinases AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in adipocyte differentiation. IUBMB Life 65: 572-583. https://doi.org/10.1002/iub.1170
  21. Inoki K, Zhu T, Guan KL. 2003. TSC2 mediates cellular energy response to control cell growth and survival. Cell 115: 577-590. https://doi.org/10.1016/S0092-8674(03)00929-2
  22. Watt MJ, Holmes AG, Pinnamaneni SK, Garnham AP, Steinberg GR, Kemp BE, Febbraio MA. 2006. Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue. Am J Physiol Endocrinol Metab 290: E500-508. https://doi.org/10.1152/ajpendo.00361.2005
  23. Jimenez-Aranda A, Fernandez-Vazquez G, Campos D, Tassi M, Velasco-Perez L, Tan DX, Reiter RJ, Agil A. 2013. Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats. J Pineal Res 55: 416-423.
  24. Seale P, Conroe HM, Estall J, Kajimura S, Frontini A, Ishibashi J, Cohen P, Cinti S, Spiegelman BM. 2011. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest 121: 96-105. https://doi.org/10.1172/JCI44271
  25. Kajimura S, Seale P, Tomaru T, Erdjument-Bromage H, Cooper MP, Ruas JL, Chin S, Tempst P, Lazar MA, Spiegelman BM. 2008. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev 22: 1397-1409. https://doi.org/10.1101/gad.1666108