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Effects of Opuntia ficus-indica on Lipid Metabolism in the db/db Mouse

노팔 복합물이 II형 당뇨생쥐에서 지질대사에 미치는 효과

  • Yoon, Jin A (Dept. of Food and Nutrition, Baewha Women's University)
  • 윤진아 (배화여자대학교 식품영양과)
  • Received : 2012.11.08
  • Accepted : 2013.05.08
  • Published : 2013.06.30

Abstract

This study investigated the effects of Opuntia ficus-indica and other natural resources (OF) in db/db and C57 mice. Plasma triglycerides, cholesterol, alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, fecal bile acid excretion, the histopathological appearance of the liver, and cholesterol-related mRNA expression were determined. Mice (12 db/db mice and 12 C57 mice) were assigned to diabetic-control (db-C), diabetic-OF treatment (db-OF), normal-control (C57-C), and normal-OF treatment (C57-OF) groups. Animals in the control group were fed an AIN-76 recommended diet and animals in the OF group were fed an experimental diet containing 5% of OF for 4 weeks. Concentrations of total plasma cholesterol, triglyceride, low density lipoprotein (LDL)-cholesterol, and very low density lipoprotein (VLDL)-cholesterol decreased with the administration of OF. In contrast, high density lipoprotein (HDL)-cholesterol levels were minimally affected by the experimental diet. Plasma AST and ALT showed lower activities in the db-OF group, and the fecal excretion of bile acid was reduced in the db-OF group. Histopathological analysis of the liver showed that fatty liver conditions in the db-OF group were more improved than db-C. Low-density lipoprotein receptor (LDL-R) and cholesterol 7${\alpha}$-hydroxylase (CYP7A1) mRNA expression were increased in the db-OF group as well. However, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA-R) mRNA expression was lower in the db-OF group. These results provide experimental evidence about improved lipid metabolism of the OF feeding in the db/db mice.

유전적으로 제2형 당뇨병이 유발되는 db/db 생쥐에 OF를 5% 수준으로 4주간 급여한 결과 지방 대사를 개선시켜, 혈장 총콜레스테롤, LDL-콜레스테롤, VLDL-콜레스테롤과 중성지방을 유의적으로(p<0.05) 감소시켰고, HDL-콜레스테롤은 유의적인 차이를 보이지 않았다. 혈장 총콜레스테롤의 감소는 간에서 HMG-CoA-R의 감소에 의한 콜레스테롤의 생성이 줄어든 것이고, 또한 콜레스테롤을 담즙산으로 합성하는 CYP7A1을 증가시켜 콜레스테롤을 담즙산의 형태로 배설시켰기 때문이다. 이 결과 분변 중 담즙산의 함량이 증가하였다. LDL-콜레스테롤의 감소는 LDL-콜레스테롤을 세포로 이동시켜 분해를 촉진하는 LDL-R의 증가로 확인할 수 있었다. db/db mice에서는 비만뿐 아니라 심각한 지방간이 유발되는데 OF의 급여로 AST와 ALT를 낮추어 간세포의 파괴를 완화시켰으며, 간 조직의 H&E 염색 소견에서도 지방간의 완화를 확인할 수 있었다. 또한 대조군으로 C57 생쥐에게 5% 수준으로 OF를 급여한 결과 OF를 급여하지 않은 대조군과 OF를 급여한 실험군의 혈장 중성지방, 총 콜레스테롤, HDL-콜레스테롤, LDL-콜레스테롤, VLDL-콜레스테롤, AST와 ALT 함량의 차이가 없었으며, 간조직 관찰에서도 차이를 나타내지 않았다. 이상의 결과를 종합할 때, OF는 당뇨병이 유발되지 않은 정상혈당의 생쥐에서는 지질대사에 아무런 영향을 주지 않았으며, 제2형 당뇨병인 db/db mice의 당뇨병 합병증인 지질대사 이상을 개선하는데 효과가 있는 것으로 사료되며, OF의 어떤 성분이 이와 같은 효과를 나타냈는지 보다 구체적인 성분 분석과 세부적인 연구를 통한 확인이 필요하다고 사료된다.

Keywords

References

  1. Yoon KH. 1999. Clinical characteristics of diabetes mellitus in Korea. Food Industry and Nutrition 4(3): 73-82.
  2. Lee TH. 1999. Diagnosis and classification of diabetes mellitus. Food Industry and Nutrition 4(2): 61-65.
  3. Kim MJ. 2001. Effect of amaranth (Amaranthus spp. L.) on lipid metabolism and serum glucose level in diabetic rats. MS Thesis. Korea University, Seoul, Korea. p 5-6.
  4. Park SH, Lee YK, Lee HS. 1994. The effectss of dietary fiber feeding on gastrointestinal functions and lipid and glucose metabolism in streptozotocin-induced diabetic rats. Korean J Nutr 27: 311-322.
  5. Holt RIG. 2010 Textbook of diabetes. 4th ed. Wiley-Blackwell, West Sussex, UK. p 56-60.
  6. O'Meara NM, Devery RA, Owens D, Collins PB, Johnson AH, Tomkin GH. 1990. Cholesterol metabolism in alloxan-induced diabetic rabbits. Diabetes 39: 629-633.
  7. Sung JH, Lee SJ, Park KH, Moon TW. 2004. Isoflavones inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase in vitro. Biosci Biotechnol Biochem 68: 428-432. https://doi.org/10.1271/bbb.68.428
  8. Brown MS, Goldstein JL. 1986. A receptor-mediated pathway for cholesterol homeostasis. Science 232: 34-47. https://doi.org/10.1126/science.3513311
  9. Han SH, Chung MJ, Lee SJ, Rhee C. 2006. Digestion-resistant fraction from soybean [Glycine max (L.) Merrill] induced hepatic LDL receptor and CYP7A1 expression in apolipoprotein E-deficient mice. J Nutr Biochem 17: 682-688. https://doi.org/10.1016/j.jnutbio.2005.11.004
  10. Tiemann M, Han Z, Soccio R, Bollineni J, Shefer S, Sehayek E, Breslow JL. 2004. Cholesterol feeding of mice expressing cholesterol $7{\alpha}$-hydroxylase increases bile acid pool size despite decreased enzyme activity. Proc Natl Acad Sci U S A 101: 1846-1851. https://doi.org/10.1073/pnas.0308426100
  11. Shin DJ, Plateroti M, Samarut S, Osborne TF. 2006. Two uniquely arranged thyroid hormone response elements in the far upstream 5' flanking region confer direct thyroid hormone regulation to the murine cholesterol $7{\alpha}$ hydroxylase gene. Nucleic Acids Res 34: 3853-3861. https://doi.org/10.1093/nar/gkl506
  12. Cardenas Medellín ML, Serna Saldivar SO, Velazco de la Garza J. 1998. Effect of raw and cooked nopal (Opuntia ficus indica) ingestion on growth and profile of total cholesterol, lipoproteins, and blood glucose in rats. Arch Latinoam Nutr 48: 316-323.
  13. Fernandez ML, Lin EC, Trejo A, McNamara DJ. 1992. Prickly pear (Opuntia sp.) pectin reverses low density lipoprotein receptor suppression induced by a hypercholesterolemic diet in guinea pigs. J Nutr 122: 2330-2340.
  14. Oh PS, Lim KT. 2006. Glycoprotein (90 kDa) isolated from Opuntia ficus-indica var. saboten MAKINO lowers plasma lipid level through scavenging of intracellular radicals in triton WR-1339-induces mice. Biol Pharm Bull 29: 1391-1396. https://doi.org/10.1248/bpb.29.1391
  15. Yoon JA, Lee SJ, Kim HK, Son YS. 2011. Ameliorating effects of a nopal (Opuntia ficus-indica) complex on blood glucose in db/db mice. Food Sci Biothechnol 20: 255-299. https://doi.org/10.1007/s10068-011-0035-4
  16. Yoon JA, Son YS. 2009. Effects of Opuntia ficus-indica complexes B (OCB) on blood glucose and lipid metabolism in streptozotocin-induced diabetic rats. Korean J Food & Nutr 22: 48-56.
  17. Lim SJ, Choi SS. 1997. The effect of Tricosanthes kiliouii Max. subfractions on the insulin activity in streptozotocin induced diabetic rats and their acute toxicity. Korean J Nutr 30: 25-31.
  18. Sima AA, Dunlap JA, Davidson EP, Wiese TJ, Lightle RL, Greene DA, Yorek MA. 1997. Supplemental myo-inositol prevents L-fucose-induced diabetic neuropathy. Diabetes 46: 301-306. https://doi.org/10.2337/diabetes.46.2.301
  19. Yadav UC, Moorthy K, Baquer NZ. 2004. Effects of sodium- orthovanadate and Trigonella foenum-graecum seeds on hepatic and renal lipogenic enzymes and lipid profile during alloxan diabetes. J Biosci 29: 81-91. https://doi.org/10.1007/BF02702565
  20. Kwack KH, Kim SH, Song HJ. 1993. The effects of Yukmijihwangtang & Discoreae radix on the changes of blood glucose & serum in diabetic rats induced by alloxan. J Orietal Medical Pathology 8: 137-156.
  21. Xie JT, Aung HH, Wu JA, Attel AS, Yuan CS. 2002. Effects of American ginseng berry extract on blood glucse levels in ob/ob mice. Am J Chin Med 30: 187-194. https://doi.org/10.1142/S0192415X02000442
  22. Warnick GR, Knopp RH, Fitzpatrick V, Branson L. 1990. Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints. Clin Chem 36:15-19.
  23. Reitman S, Frankel S. 1957. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28: 56-63.
  24. Fausa O, Skalhegg BA. 1974. Quantitative determination of bile acids and their conjugates using thin-layer chromatography and a purified $3{\alpha}$-hydroxysteroid dehydrogenase. Scand J Gastroenterol 9: 249-254.
  25. Yoon JA. 2007. Effect of Opuntia ficus-indica complexes on blood glucose and lipid metabolism in animal model of type I and type II diabetes. PhD Dissertation. Korea University, Seoul, Korea. p 55-58.
  26. Yajima K, Hirose H, Fujita H, Seto Y, Fujita H, Ukeda K, Miyashita K, Kawai T, Yamamoto Y, Ogawa T, Yamada T, Saruta T. 2003. Combination therapy with $PPAR{\gamma}$ and $PPAR{\alpha}$ agonists increases glucose-stimulated insulin secretion in db/db mice. Am J Physiol Endocrinol Metab 284:E966-E971.
  27. Kawasaki F, Matsuda M, Kanda Y, Inoue H, Kaku K. 2005. Structural and functional analysis of pancreatic islets preserved by pioglitazone in db/db mice. Am J Physiol Endocrinol Metab 288: E510-E518.
  28. Utsunomiya H, Yamakawa T, Kamei J, Kadonosono K, Tanaka S. 2005. Anti-hyperglycemic effects of plum in a rat model of obesity and type 2 diabetes, Wister fatty rat. Biomed Res 26: 193-200. https://doi.org/10.2220/biomedres.26.193
  29. MacLean PS, Bower JF, Vadlamudi S, Osborne JN, Bradfield JF, Burden HW, Bensch WH, Kauffman RF, Barakat HA. 2003. Cholesteryl ester transfer protein expression prevents diet-induced atherosclerotic lesions in male db/db mice. Arterioscler Thromb Vasc Biol 23: 1412-1415. https://doi.org/10.1161/01.ATV.0000080687.94313.67
  30. Bursch W, Schulte-Hermann R. 1986. Cytoprotective effect of the prostacyclin derivative iloprost against liver cell death induced by the hepatotoxins carbon tetracholoride and brombenzen. Klin Wochenschr 7: 47-50.
  31. Jeong KS. 2003. Effects of Bambusae Caulis in Liquamen obtained from different production process on blood sugar in db/db mice. PhD Dissertation. Dong-shin University, Jeonnam, Korea.
  32. Han KH, Iijuka M, Shimada KI, Sekikawa M, Kuramochi K, Ohba K, Ruvini L, Chiji H, Fukushima M. 2005. Azuki resistant starch lowered serum cholesterol and hepatic 3-hydroxy-3-methylglutaryl-CoA mRNA levels and increased hepatic LDL-receptor and cholesterol $7{\alpha}$-hydroxylase mRNA levels in rats fed a cholesterol diet. Br J Nutr 94: 902-908. https://doi.org/10.1079/BJN20051598
  33. Xu A, Lam MC, Chan KW, Wang Y, Zhang J, Hoo RL, Xu JY, Chen B, Chow WS, Tso AW, Lam KS. 2005. Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice. Proc Natl Acad Sci U S A 102: 6086-6091. https://doi.org/10.1073/pnas.0408452102
  34. Choi YS, Lee SY. 1992. Serum cholesterol and 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Korean Soc Food Nutr 21: 580-593.

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