Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/35797
標題: Lucidone作用於抑制脂質新生及減緩高油脂飼料造成的肥胖與代謝失調之效果
Effects of lucidone on suppressing adipogenesis and attenuating obesity and consequent metabolic disorders in high-fat diet mice
作者: 謝瑀心
Hsieh, Yu-Hsin
關鍵字: 紅果釣樟;Lindera erythrocarpa Makino;脂質新生;高油脂飼料誘導肥胖;Adipogenesis;Diet-induced obesity
出版社: 生物科技學研究所
引用: 1. Nawrocki AR, Scherer PE. Keynote review: the adipocyte as a drug discovery target. Drug Discovery Today 2005, 10:1219-1230. 2. 2012 Statistics of Causes of Death. Department of Health, Executive Yuan, Taiwan. 3. Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff (Millwood) 2009, 28:w822-831. 4. Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends in Endocrinology & Metabolism 2000, 11:327-332. 5. Nicholls DG, Locke RM. Thermogenic mechanisms in brown fat. Physiological Reviews 1984, 64:1-64. 6. Sethi JK, Vidal-Puig AJ. Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. Journal of Lipid Research 2007, 48:1253-1262. 7. Hellerstein MK. De novo lipogenesis in humans: metabolic and regulatory aspects. European Journal of Clinical Nutrition 1999, 53 Suppl 1:S53-65. 8. Foufelle F, Gouhot B, Pegorier JP, Perdereau D, Girard J, Ferre P. Glucose stimulation of lipogenic enzyme gene expression in cultured white adipose tissue. A role for glucose 6-phosphate. Journal of Biological Chemistry 1992, 267:20543-20546. 9. Bianchi A, Evans JL, Iverson AJ, Nordlund AC, Watts TD, Witters LA. Identification of an isozymic form of acetyl-CoA carboxylase. Journal of Biological Chemistry 1990, 265:1502-1509. 10. Mead JR, Irvine SA, Ramji DP. Lipoprotein lipase: structure, function, regulation, and role in disease. Journal of Molecular Medicine 2002, 80:753-769. 11. Abumrad NA, El-Maghrabi MR, Amri EZ, Lopez E, Grimaldi PA. Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. Journal of Biological Chemistry 1993, 268:17665-17668. 12. Schaffer JE, Lodish HF. Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein. Cell 1994, 79:427-436. 13. Trigatti BL, Anderson RG, Gerber GE. Identification of caveolin-1 as a fatty acid binding protein. Biochemical and Biophysical Research Communications 1999, 255:34-39. 14. Schwieterman W, Sorrentino D, Potter BJ, Rand J, Kiang CL, Stump D, Berk PD. Uptake of oleate by isolated rat adipocytes is mediated by a 40-kDa plasma membrane fatty acid binding protein closely related to that in liver and gut. Proceedings of the National Academy of Sciences of the United States of America 1988, 85:359-363. 15. Febbraio M, Abumrad NA, Hajjar DP, Sharma K, Cheng W, Pearce SF, Silverstein RL. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. Journal of Biological Chemistry 1999, 274:19055-19062. 16. Coburn CT, Knapp FF, Jr., Febbraio M, Beets AL, Silverstein RL, Abumrad NA. Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice. Journal of Biological Chemistry 2000, 275:32523-32529. 17. Gesta S, Kahn CR, Rayalam S, Baile CA. Adipose tissue biology. Symonds ME. New York: Springer; 2011. 18. Rodbell M. Localization of lipoprotein lipase in fat cells of rat adipose tissue. Journal of Biological Chemistry 1964, 239:753-755. 19. Mohamed-Ali V, Pinkney JH, Coppack SW. Adipose tissue as an endocrine and paracrine organ. International Journal of Obesity and Related Metabolic Disorders 1998, 22:1145-1158. 20. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372:425-432. 21. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004, 145:2273-2282. 22. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Wool EA, Monroe CA, Tepper RI. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995, 83:1263-1271. 23. Elmquist JK, Elias CF, Saper CB. From lesions to leptin: hypothalamic control of food intake and body weight. Neuron 1999, 22:221-232. 24. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, Kern PA, Friedman JM. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Medicine 1995, 1:1155-1161. 25. Yang R, Barouch LA. Leptin signaling and obesity: cardiovascular consequences. Circulation Research 2007, 101:545-559. 26. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. Journal of Biological Chemistry 1995, 270:26746-26749. 27. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. Journal of Biological Chemistry 1996, 271:10697-10703. 28. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003, 423:762-769. 29. Bjursell M, Ahnmark A, Bohlooly YM, William-Olsson L, Rhedin M, Peng XR, Ploj K, Gerdin AK, Arnerup G, Elmgren A, Berg AL, Oscarsson J, Linden D. Opposing effects of adiponectin receptors 1 and 2 on energy metabolism. Diabetes 2007, 56:583-593. 30. Avram MM, Avram AS, James WD. Subcutaneous fat in normal and diseased states 3. Adipogenesis: from stem cell to fat cell. Journal of the American Academy of Dermatology 2007, 56:472-492. 31. Kelly KA, Gimble JM. 1,25-Dihydroxy vitamin D3 inhibits adipocyte differentiation and gene expression in murine bone marrow stromal cell clones and primary cultures. Endocrinology 1998, 139:2622-2628. 32. Lee J, Jung E, Kim S, Huh S, Kim Y, Byun SY, Kim YS, Park D. Isorhamnetin represses adipogenesis in 3T3-L1 cells. Obesity (Silver Spring) 2009, 17:226-232. 33. Green H, Kehinde O. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell 1975, 5:19-27. 34. Wang Y, Kim KA, Kim JH, Sul HS. Pref-1, a preadipocyte secreted factor that inhibits adipogenesis. Journal of Nutrition 2006, 136:2953-2956. 35. Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiological Reviews 1998, 78:783-809. 36. Tang QQ, Otto TC, Lane MD. Mitotic clonal expansion: a synchronous process required for adipogenesis. Proceedings of the National Academy of Sciences of the United States of America 2003, 100:44-49. 37. Tang QQ, Otto TC, Lane MD. CCAAT/enhancer-binding protein beta is required for mitotic clonal expansion during adipogenesis. Proceedings of the National Academy of Sciences of the United States of America 2003, 100:850-855. 38. Tanaka T, Yoshida N, Kishimoto T, Akira S. Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene. EMBO Journal 1997, 16:7432-7443. 39. Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, Spiegelman BM. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes & Development 2002, 16:22-26. 40. Farmer SR. Transcriptional control of adipocyte formation. Cell metabolism 2006, 4:263-273. 41. Spiegelman BM, Frank M, Green H. Molecular cloning of mRNA from 3T3 adipocytes. Regulation of mRNA content for glycerophosphate dehydrogenase and other differentiation-dependent proteins during adipocyte development. J Biol Chem 1983, 258:10083-10089. 42. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. Journal of Clinical Investigation 1995, 95:2409-2415. 43. Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. Journal of Clinical Investigation 1995, 95:2111-2119. 44. Yamakawa T, Tanaka S, Yamakawa Y, Kiuchi Y, Isoda F, Kawamoto S, Okuda K, Sekihara H. Augmented production of tumor necrosis factor-alpha in obese mice. Clinical Immunology and Immunopathology 1995, 75:51-56. 45. Hotamisligil GS, Spiegelman BM. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes 1994, 43:1271-1278. 46. Xing H, Northrop JP, Grove JR, Kilpatrick KE, Su JL, Ringold GM. TNF alpha-mediated inhibition and reversal of adipocyte differentiation is accompanied by suppressed expression of PPARgamma without effects on Pref-1 expression. Endocrinology 1997, 138:2776-2783. 47. Petruschke T, Hauner H. Tumor necrosis factor-alpha prevents the differentiation of human adipocyte precursor cells and causes delipidation of newly developed fat cells. The Journal of Clinical Endocrinology and Metabolism 1993, 76:742-747. 48. Zhang B, Berger J, Hu E, Szalkowski D, White-Carrington S, Spiegelman BM, Moller DE. Negative regulation of peroxisome proliferator-activated receptor-gamma gene expression contributes to the antiadipogenic effects of tumor necrosis factor-alpha. Molecular Endocrinology 1996, 10:1457-1466. 49. Prins JB, Niesler CU, Winterford CM, Bright NA, Siddle K, O''Rahilly S, Walker NI, Cameron DP. Tumor necrosis factor-alpha induces apoptosis of human adipose cells. Diabetes 1997, 46:1939-1944. 50. Qian H, Hausman DB, Compton MM, Martin RJ, Della-Fera MA, Hartzell DL, Baile CA. TNFalpha induces and insulin inhibits caspase 3-dependent adipocyte apoptosis. Biochemical and Biophysical Research Communications 2001, 284:1176-1183. 51. Huang C, Zhang Y, Gong Z, Sheng X, Li Z, Zhang W, Qin Y. Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway. Biochemical and Biophysical Research Communications 2006, 348:571-578. 52. Choi BH, Ahn IS, Kim YH, Park JW, Lee SY, Hyun CK, Do MS. Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte. Experimental and Molecular Medicine 2006, 38:599-605. 53. Hwang JT, Park IJ, Shin JI, Lee YK, Lee SK, Baik HW, Ha J, Park OJ. Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochemical and Biophysical Research Communications 2005, 338:694-699. 54. Chen S, Li Z, Li W, Shan Z, Zhu W. Resveratrol inhibits cell differentiation in 3T3-L1 adipocytes via activation of AMPK. Canadian Journal of Physiology and Pharmacology 2011, 89:793-799. 55. Hsu CL, Yen GC. Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells. Journal of Agricultural and Food Chemistry 2007, 55:1730-1736. 56. Harmon AW, Harp JB. Differential effects of flavonoids on 3T3-L1 adipogenesis and lipolysis. American journal of physiology: Cell physiology 2001, 280:C807-813. 57. Lin J, Della-Fera MA, Baile CA. Green tea polyphenol epigallocatechin gallate inhibits adipogenesis and induces apoptosis in 3T3-L1 adipocytes. Obesity Research 2005, 13:982-990. 58. Ejaz A, Wu D, Kwan P, Meydani M. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. Journal of Nutrition 2009, 139:919-925. 59. Lee YK, Lee WS, Hwang JT, Kwon DY, Surh YJ, Park OJ. Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 in cancer cells. Journal of Agricultural and Food Chemistry 2009, 57:305-310. 60. Muthusamy VS, Anand S, Sangeetha KN, Sujatha S, Arun B, Lakshmi BS. Tannins present in Cichorium intybus enhance glucose uptake and inhibit adipogenesis in 3T3-L1 adipocytes through PTP1B inhibition. Chemico-Biological Interactions 2008, 174:69-78. 61. Strobel P, Allard C, Perez-Acle T, Calderon R, Aldunate R, Leighton F. Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. The Biochemical journal 2005, 386:471-478. 62. Hsu CL, Yen GC. Induction of cell apoptosis in 3T3-L1 pre-adipocytes by flavonoids is associated with their antioxidant activity. Molecular Nutrition & Food Research 2006, 50:1072-1079. 63. Ahn J, Lee H, Kim S, Park J, Ha T. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochemical and Biophysical Research Communications 2008, 373:545-549. 64. Rayalam S, Della-Fera MA, Baile CA. Phytochemicals and regulation of the adipocyte life cycle. The Journal of Nutritional Biochemistry 2008, 19:717-726. 65. Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. The American Journal of Clinical Nutrition 1999, 70:1040-1045. 66. Vermaak I, Hamman JH, Viljoen AM. Hoodia gordonii: an up-to-date review of a commercially important anti-obesity plant. Planta Medica 2011, 77:1149-1160. 67. Van Heerden FR, Marthinus Horak R, Maharaj VJ, Vleggaar R, Senabe JV, Gunning PJ. An appetite suppressant from Hoodia species. Phytochemistry 2007, 68:2545-2553. 68. MacLean DB, Luo LG. Increased ATP content/production in the hypothalamus may be a signal for energy-sensing of satiety: studies of the anorectic mechanism of a plant steroidal glycoside. Brain Research 2004, 1020:1-11. 69. Whelan AM, Jurgens TM, Szeto V. Case report. Efficacy of Hoodia for weight loss: is there evidence to support the efficacy claims? Journal of Clinical Pharmacy and Therapeutics 2010, 35:609-612. 70. Pushparaj PN, Low HK, Manikandan J, Tan BK, Tan CH. Anti-diabetic effects of Cichorium intybus in streptozotocin-induced diabetic rats. Journal of Ethnopharmacology 2007, 111:430-434. 71. Ghamarian A, Abdollahi M, Su X, Amiri A, Ahadi A, Nowrouzi A. Effect of chicory seed extract on glucose tolerance test (GTT) and metabolic profile in early and late stage diabetic rats. DARU Journal of Pharmaceutical Sciences 2012, 20:56. 72. Guo H, Ling W, Wang Q, Liu C, Hu Y, Xia M, Feng X, Xia X. Effect of anthocyanin-rich extract from black rice (Oryza sativa L. indica) on hyperlipidemia and insulin resistance in fructose-fed rats. Plant Foods for Human Nutrition 2007, 62:1-6. 73. Eidi A, Eidi M, Esmaeili E. Antidiabetic effect of garlic (Allium sativum L.) in normal and streptozotocin-induced diabetic rats. Phytomedicine 2006, 13:624-629. 74. Ashraf R, Khan RA, Ashraf I. Garlic (Allium sativum) supplementation with standard antidiabetic agent provides better diabetic control in type 2 diabetes patients. Pakistan Journal of Pharmaceutical Sciences 2011, 24:565-570. 75. Rizwan Ashraf M. Phil, Rafeeq Alam Khan, Imran Ashraf. Effects of garlic on blood glucose levels and HbA1c in patients with type 2 diabetes mellitus. Journal of Medicinal Plants Research 2011, 5:2922-2928. 76. Martha Thomson ZMA-A, Khaled K. Al-Qattan, Lemia H. Shaban and Muslim Ali. Anti-diabetic and hypolipidaemic properties of garlic (Allium sativum) in streptozotocin-induced diabetic rats. International Journal of Diabetes and Metabolism 2007, 15:108-115. 77. Kumar S, Vasudeva N, Sharma S. GC-MS analysis and screening of antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala oil in streptozotocin induced diabetes mellitus in rats. Cardiovascular Diabetology 2012, 11:95. 78. Kannappan S, Jayaraman T, Rajasekar P, Ravichandran MK, Anuradha CV. Cinnamon bark extract improves glucose metabolism and lipid profile in the fructose-fed rat. Singapore Medical Journal 2006, 47:858-863. 79. Ranasinghe P, Perera S, Gunatilake M, Abeywardene E, Gunapala N, Premakumara S, Perera K, Lokuhetty D, Katulanda P. Effects of Cinnamomum zeylanicum (Ceylon cinnamon) on blood glucose and lipids in a diabetic and healthy rat model. Pharmacognosy Research 2012, 4:73-79. 80. Lu T, Sheng H, Wu J, Cheng Y, Zhu J, Chen Y. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes. Nutrition Research 2012, 32:408-412. 81. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003, 26:3215-3218. 82. Mang B, Wolters M, Schmitt B, Kelb K, Lichtinghagen R, Stichtenoth DO, Hahn A. Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. European Journal of Clinical Investigation 2006, 36:340-344. 83. Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial. The Journal of the American Board of Family Medicine 2009, 22:507-512. 84. Gnoni GV, Paglialonga G, Siculella L. Quercetin inhibits fatty acid and triacylglycerol synthesis in rat-liver cells. European Journal of Clinical Investigation 2009, 39:761-768. 85. Kobori M, Masumoto S, Akimoto Y, Oike H. Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57/BL6J mice. Molecular Nutrition & Food Research 2010. 86. De Smet E, Mensink RP, Plat J. Effects of plant sterols and stanols on intestinal cholesterol metabolism: suggested mechanisms from past to present. Molecular Nutrition & Food Research 2012, 56:1058-1072. 87. Urizar NL, Moore DD. GUGULIPID: a natural cholesterol-lowering agent. Annual Review of Nutrition 2003, 23:303-313. 88. Xia X, Ling W, Ma J, Xia M, Hou M, Wang Q, Zhu H, Tang Z. An anthocyanin-rich extract from black rice enhances atherosclerotic plaque stabilization in apolipoprotein E-deficient mice. Journal of Nutrition 2006, 136:2220-2225. 89. Banerjee SK, Maulik SK. Effect of garlic on cardiovascular disorders: a review. Nutrition Journal 2002, 1:4. 90. Ichino K, Tanaka H, Ito K, Tanaka T, Mizuno M. Two New Dihydrochalcones from Lindera erythrocarpa. Journal of Natural Products 1988, 51:915-917. 91. S.Y. Liu SH, I. Inagaki. Terpenes of Lindera erythrocarpa. Phytochemistry 1973, 12:233. 92. Flora of Taiwan, 2nd edition. (Boufford D.E. OH ed., vol. 2. pp. 460: Editorial Committee of the Flora of Taiwan; 1996:460. 93. Oh HM, Choi SK, Lee JM, Lee SK, Kim HY, Han DC, Kim HM, Son KH, Kwon BM. Cyclopentenediones, inhibitors of farnesyl protein transferase and anti-tumor compounds, isolated from the fruit of Lindera erythrocarpa Makino. Bioorganic & Medicinal Chemistry 2005, 13:6182-6187. 94. Kumar KJ, Wang SY. Lucidone inhibits iNOS and COX-2 expression in LPS-induced RAW 264.7 murine macrophage cells via NF-kappaB and MAPKs signaling pathways. Planta Medica 2009, 75:494-500. 95. Wang SY, Lan XY, Xiao JH, Yang JC, Kao YT, Chang ST. Antiinflammatory activity of Lindera erythrocarpa fruits. Phytotherapy research 2008, 22:213-216. 96. Senthil Kumar KJ, Hsieh HW, Wang SY. Anti-inflammatory effect of lucidone in mice via inhibition of NF-kappaB/MAP kinase pathway. International Immunopharmacology 2010, 10:385-392. 97. Senthil Kumar KJ, Liao JW, Xiao JH, Gokila Vani M, Wang SY. Hepatoprotective effect of lucidone against alcohol-induced oxidative stress in human hepatic HepG2 cells through the up-regulation of HO-1/Nrf-2 antioxidant genes. Toxicology in vitro : an international journal published in association with BIBRA 2012, 26:700-708. 98. Chen WC, Wang SY, Chiu CC, Tseng CK, Lin CK, Wang HC, Lee JC. Lucidone suppresses hepatitis C virus replication by Nrf2-mediated heme oxygenase-1 induction. Antimicrobial Agents and Chemotherapy 2013, 57:1180-1191. 99. Senthil Kumar KJ, Yang HL, Tsai YC, Hung PC, Chang SH, Lo HW, Shen PC, Chen SC, Wang HM, Wang SY, Chou CW, Hseu YC. Lucidone protects human skin keratinocytes against free radical-induced oxidative damage and inflammation through the up-regulation of HO-1/Nrf2 antioxidant genes and down-regulation of NF-kappaB signaling pathways. Food and Chemical Toxicology 2013, 59:55-66. 100. Senthil Kumar KJ, Yang JC, Chu FH, Chang ST, Wang SY. Lucidone, a novel melanin inhibitor from the fruit of Lindera erythrocarpa Makino. Phytotherapy Research 2010, 24:1158-1165. 101. Lin CT, Senthil Kumar KJ, Tseng YH, Wang ZJ, Pan MY, Xiao JH, Chien SC, Wang SY. Anti-inflammatory activity of Flavokawain B from Alpinia pricei Hayata. Journal of Agricultural and Food Chemistry 2009, 57:6060-6065. 102. Keenan KP, Ballam GC, Dixit R, Soper KA, Laroque P, Mattson BA, Adams SP, Coleman JB. The effects of diet, overfeeding and moderate dietary restriction on Sprague-Dawley rat survival, disease and toxicology. The Journal of nutrition 1997, 127:851S-856S. 103. Dennis G, Jr., Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biology 2003, 4:P3. 104. Barbee RW, Perry BD, Re RN, Murgo JP. Microsphere and dilution techniques for the determination of blood flows and volumes in conscious mice. American Journal of Physiology 1992, 263:R728-733. 105. Suratt BT, Petty JM, Young SK, Malcolm KC, Lieber JG, Nick JA, Gonzalo JA, Henson PM, Worthen GS. Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis. Blood 2004, 104:565-571. 106. Cawthorn WP, Sethi JK. TNF-alpha and adipocyte biology. FEBS Letters 2008, 582:117-131. 107. Tejerina S, De Pauw A, Vankoningsloo S, Houbion A, Renard P, De Longueville F, Raes M, Arnould T. Mild mitochondrial uncoupling induces 3T3-L1 adipocyte de-differentiation by a PPARgamma-independent mechanism, whereas TNFalpha-induced de-differentiation is PPARgamma dependent. Journal of Cell Science 2009, 122:145-155. 108. Souza SC, Palmer HJ, Kang YH, Yamamoto MT, Muliro KV, Paulson KE, Greenberg AS. TNF-alpha induction of lipolysis is mediated through activation of the extracellular signal related kinase pathway in 3T3-L1 adipocytes. Journal of Cellular Biochemistry 2003, 89:1077-1086. 109. Faulds MH, Zhao C, Dahlman-Wright K. Molecular biology and functional genomics of liver X receptors (LXR) in relationship to metabolic diseases. Current Opinion in Pharmacology 2010, 10:692-697. 110. Huber RM, Murphy K, Miao B, Link JR, Cunningham MR, Rupar MJ, Gunyuzlu PL, Haws TF, Kassam A, Powell F, Hollis GF, Young PR, Mukherjee R, Burn TC. Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters. Gene 2002, 290:35-43. 111. Cariou B, Staels B. FXR: a promising target for the metabolic syndrome? Trends in Pharmacological Sciences 2007, 28:236-243. 112. Claudel T, Sturm E, Duez H, Torra IP, Sirvent A, Kosykh V, Fruchart JC, Dallongeville J, Hum DW, Kuipers F, Staels B. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element. Journal of Clinical Investigation 2002, 109:961-971. 113. Biddinger SB, Miyazaki M, Boucher J, Ntambi JM, Kahn CR. Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin and sterol regulatory element-binding protein-1c. Diabetes 2006, 55:2032-2041. 114. Cohen P, Miyazaki M, Socci ND, Hagge-Greenberg A, Liedtke W, Soukas AA, Sharma R, Hudgins LC, Ntambi JM, Friedman JM. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 2002, 297:240-243. 115. Biddinger SB, Almind K, Miyazaki M, Kokkotou E, Ntambi JM, Kahn CR. Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome. Diabetes 2005, 54:1314-1323. 116. Ntambi JM, Kim Y-C. Adipocyte differentiation and gene expression. The Journal of Nutrition 2000, 130:3122S-3126S. 117. Ntambi JM, Young-Cheul K. Adipocyte differentiation and gene expression. The Journal of nutrition 2000, 130:3122S-3126S. 118. Raghow R, Yellaturu C, Deng X, Park EA, Elam MB. SREBPs: the crossroads of physiological and pathological lipid homeostasis. Trends in Endocrinology & Metabolism 2008, 19:65-73. 119. Le Lay S, Lefrere I, Trautwein C, Dugail I, Krief S. Insulin and sterol-regulatory element-binding protein-1c (SREBP-1C) regulation of gene expression in 3T3-L1 adipocytes. Identification of CCAAT/enhancer-binding protein beta as an SREBP-1C target. Journal of Biological Chemistry 2002, 277:35625-35634. 120. Prusty D, Park BH, Davis KE, Farmer SR. Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma ) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes. Journal of Biological Chemistry 2002, 277:46226-46232. 121. Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARgamma. Annual Review of Biochemistry 2008, 77:289-312. 122. He W, Barak Y, Hevener A, Olson P, Liao D, Le J, Nelson M, Ong E, Olefsky JM, Evans RM. Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. Proceedings of the National Academy of Sciences of the United States of America 2003, 100:15712-15717. 123. Yamauchi T, Kamon J, Waki H, Murakami K, Motojima K, Komeda K, Ide T, Kubota N, Terauchi Y, Tobe K, Miki H, Tsuchida A, Akanuma Y, Nagai R, Kimura S, Kadowaki T. The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. Journal of Biological Chemistry 2001, 276:41245-41254. 124. Wilson PW, D''Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998, 97:1837-1847. 125. Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN. Diet-induced type II diabetes in C57BL/6J mice. Diabetes 1988, 37:1163-1167. 126. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation 2003, 112:1821-1830. 127. Calder PC, Ahluwalia N, Brouns F, Buetler T, Clement K, Cunningham K, Esposito K, Jonsson LS, Kolb H, Lansink M, Marcos A, Margioris A, Matusheski N, Nordmann H, O''Brien J, Pugliese G, Rizkalla S, Schalkwijk C, Tuomilehto J, Warnberg J, Watzl B, Winklhofer-Roob BM. Dietary factors and low-grade inflammation in relation to overweight and obesity. British Journal of Nutrition 2011, 106 Suppl 3:S5-78. 128. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993, 259:87-91. 129. Ros Perez M, Medina-Gomez G. Obesity, adipogenesis and insulin resistance. Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion 2011, 58:360-369. 130. Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 2001, 413:131-138. 131. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature 2000, 405:421-424. 132. Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, Minnemann T, Shulman GI, Kahn BB. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 2001, 409:729-733. 133. Dadson K, Liu Y, Sweeney G. Adiponectin action: a combination of endocrine and autocrine/paracrine effects. Frontiers in endocrinology 2011, 2:62. 134. Daimon M, Oizumi T, Saitoh T, Kameda W, Hirata A, Yamaguchi H, Ohnuma H, Igarashi M, Tominaga M, Kato T, Funagata s. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population: the Funagata study. Diabetes Care 2003, 26:2015-2020. 135. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, Nagai M, Matsuzawa Y, Funahashi T. Adiponectin as a biomarker of the metabolic syndrome. Circulation Journal 2004, 68:975-981. 136. Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF. Adiponectin and protection against type 2 diabetes mellitus. The Lancet 2003, 361:226-228. 137. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. Journal of Clinical Endocrinology & Metabolism 2001, 86:1930-1935. 138. Hui X, Lam KS, Vanhoutte PM, Xu A. Adiponectin and cardiovascular health: an update. British Journal of Pharmacology 2012, 165:574-590. 139. Siasos G, Tousoulis D, Kollia C, Oikonomou E, Siasou Z, Stefanadis C, Papavassiliou AG. Adiponectin and cardiovascular disease: mechanisms and new therapeutic approaches. Current Medicinal Chemistry 2012, 19:1193-1209. 140. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nature Medicine 2002, 8:1288-1295. 141. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature Medicine 2001, 7:941-946. 142. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, Uchida S, Ito Y, Takakuwa K, Matsui J, Takata M, Eto K, Terauchi Y, Komeda K, Tsunoda M, Murakami K, Ohnishi Y, Naitoh T, Yamamura K, Ueyama Y, Froguel P, Kimura S, Nagai R, Kadowaki T. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. Journal of Biological Chemistry 2003, 278:2461-2468. 143. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nature Medicine 2002, 8:731-737. 144. Combs TP, Pajvani UB, Berg AH, Lin Y, Jelicks LA, Laplante M, Nawrocki AR, Rajala MW, Parlow AF, Cheeseboro L, Ding YY, Russell RG, Lindemann D, Hartley A, Baker GR, Obici S, Deshaies Y, Ludgate M, Rossetti L, Scherer PE. A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity. Endocrinology 2004, 145:367-383. 145. Glue P, Clement RP. Cytochrome P450 enzymes and drug metabolism--basic concepts and methods of assessment. Cellular and Molecular Neurobiology 1999, 19:309-323. 146. Guengerich FP. Cytochrome p450 and chemical toxicology. Chemical Research in Toxicology 2008, 21:70-83. 147. Stromstedt M, Rozman D, Waterman MR. The ubiquitously expressed human CYP51 encodes lanosterol 14 alpha-demethylase, a cytochrome P450 whose expression is regulated by oxysterols. Archives of Biochemistry and Biophysics 1996, 329:73-81. 148. Lorbek G, Lewinska M, Rozman D. Cytochrome P450s in the synthesis of cholesterol and bile acids--from mouse models to human diseases. FEBS Journal 2012, 279:1516-1533. 149. Zhang L, Zuo Z, Lin G. Intestinal and hepatic glucuronidation of flavonoids. Molecular Pharmaceutics 2007, 4:833-845. 150. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Molecular Pharmaceutics 2007, 4:807-818. 151. Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences of the United States of America 2004, 101:15718-15723. 152. Cho I, Yamanishi S, Cox L, Methe BA, Zavadil J, Li K, Gao Z, Mahana D, Raju K, Teitler I, Li H, Alekseyenko AV, Blaser MJ. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 2012, 488:621-626. 153. Yan D, Jin C, Xiao XH, Dong XP. Antimicrobial properties of berberines alkaloids in Coptis chinensis Franch by microcalorimetry. Journal of Biochemical and Biophysical Methods 2008, 70:845-849. 154. Freile ML, Giannini F, Pucci G, Sturniolo A, Rodero L, Pucci O, Balzareti V, Enriz RD. Antimicrobial activity of aqueous extracts and of berberine isolated from Berberis heterophylla. Fitoterapia 2003, 74:702-705. 155. Iwazaki RS, Endo EH, Ueda-Nakamura T, Nakamura CV, Garcia LB, Filho BP. In vitro antifungal activity of the berberine and its synergism with fluconazole. A
摘要: 
The incidence of obesity has increased dramatically worldwide over the last few decades because of the life style changes. Obesity is associated with an increased risk of a spectrum of diseases, including malignancy, heart disease, cerebrovascular disease, type 2 diabetes, hypertension, hyperlipidemia and others. In this study, we investigated the effects of lucidone, an extract from the fruit of Lindera erythrocarpa Makino, in vitro on anti-adipogenesis in 3T3-L1 cells and in vivo on high-fat diet (60% energy from fat) induced obesity in C57BL/6 mice. Our data showed that lucidone suppressed adipogenesis in 3T3-L1 cells in a dose dependent manner and reduced the transcriptional levels of several adipogenic genes, including PPAR-gamma, C/EBP-alpha, LXR-alpha, LPL, aP2, GLUT4 and adiponectin, without affecting cell cycle. A group of 5-week-old male C57BL/6 mice fed a high-fat diet supplemented with lucidone at a dosage of 138.75 mg/kg for 12 weeks showed lowered body and liver weights, decreased food efficiency, and lowered levels of serum cholesterol, TG, glucose and insulin. Dissection of adipose tissue from lucidone-fed mice showed reductions in the average and proportions of fat-cell size. At the molecular level, the adipocytic GLUT4 and CD36 levels were induced by dietary lucidone that may contribute to the improvement of insulin sensitivity, hyperglycemia and hyperlipidemia. Adiponectin, which was highly induced in LSH/H mice, may be a vital factor that promotes energy expenditure and alleviates body weight gain. Moreover, systemic analysis of hepatic gene expression profile showed that dietary lucidone modulates some gene expression involved in lipid and glucose metabolism. Taken together, this study reveals the potential of lucidone as a nutraceutical for preventing obesity and consequent metabolic disorders under unhealthy eating habits.

由於人們生活及飲食習慣的改變,已開發國家的肥胖人口數量在過去幾十年間正急劇增加。肥胖已知會提高罹患多種疾病的風險,包括惡性腫瘤、心臟病、腦血管疾病、第二型糖尿病、高血壓和高血脂等等。在本篇研究中,我們選擇來自紅果釣樟(Lindera erythrocarpa Makino)果實的活性成分lucidone作為目標天然物,在體外試驗中發現lucidone能夠在不影響細胞週期的情況下有效抑制脂質新生,且其效果與劑量呈現正相關;進一步分析其分子層次的影響發現lucidone能夠抑制多種參與脂質形成之基因的表現量,包括PPAR-gamma, C/EBP-alpha, LXR-alpha, LPL, aP2, GLUT4 以及adiponectin。體內試驗方面,持續十二週以高油脂飼料餵食五週齡C57BL/6之雄性小鼠並同時補充lucidone (138.75毫克/每公斤體重),相較於單純餵食高油脂飼料之控制組,攝取lucidone明顯減緩小鼠的體重變化,減少肝臟及脂肪組織重量,降低飼料效率,以及減少血液中的膽固醇、三酸甘油脂、胰島素及血糖濃度。脂肪組織之切片顯示,餵食lucidone能夠有效降低脂肪細胞的平均大小及其分佈比例。分子層次上,lucidone能夠誘導脂肪組織的GLUT4和CD36之表現,此現象可能有助於提高胰島素的敏感性,改善高血糖和高血脂的狀況。同時,lucidone明顯誘發adiponectin的表現量,此現象可能在提高能量代謝上扮演一定之重要的角色,藉以降低體內的能量儲存進而減緩體重增加。最後,我們利用微陣列分析lucidone對肝臟基因表現的影響,發現其影響不同基因參與脂質及糖類代謝的多條生化途徑,包括膽固醇生合成、脂肪酸合成、脂肪酸氧化作用。綜合以上發現,本篇研究顯示lucidone具有相當高的潛力開發為植物藥,應用於預防不健康飲食習慣所造成的肥胖,進而改善由肥胖所引發的代謝功能失調。
URI: http://hdl.handle.net/11455/35797
其他識別: U0005-2808201310005800
Appears in Collections:生物科技學研究所

Show full item record
 

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.