Translated Titles

Effects of rutin supplementation on metabolic syndrome features and immunomodulation using murine and cell models





Key Words

代謝症候群 ; 芸香素 ; C57BL/6雄鼠 ; 3T3-L1脂肪細胞 ; 細胞激素 ; 抗發炎 ; 免疫調節 ; metabolic syndrome ; rutin ; male C57BL/6 mice ; 3T3-L1 adipocytes ; cytokines ; anti-inflammation ; immunomodulation



Volume or Term/Year and Month of Publication


Academic Degree Category




Content Language


Chinese Abstract


English Abstract

Metabolic syndrome features include abdominal obesity, hypertriglyceridaemia, low level in high-density lipoprotein cholesterol (HDL-c), hypertension and high level in fasting glucose. Metabolic syndrome is a cluster of cardiovascular risk factors that predispose an individual to develop cardiovascular diseases and type 2 diabetes. Rutin widely exists in various foods, including buckwheat, parsley, tomatoes and apricots. It has been shown to exert important biological activities, such as antimicrobial, anti-inflammatory, antioxidant, antiviral and antiulcerogenic effects. However, the effect of rutin supplementation on metabolic syndrome and immunomodulation is still not clear. Therefore, the study investigated effects of rutin on metabolic syndrome features, inflammation and Th1/Th2 immune balance using a high-fat diet fed murine model that induced metabolic syndrome, and the modulation of inflammation and differentiation of preadipocytes.The animal model was further devided into two models including preventive and curative models. A 50% high-fat diet was used to induce metabolic syndrome in male C57BL/6 mice. Lipopolysaccharide (LPS) was used to induce pro-inflammatory cytokines secreted by 3T3-L1 preadipocytes. The results showed that rutin supplementation markedly reduced body weight, epididymal fat, energy efficiency, fasting blood glucose, TG, cholesterol, LDL-c, spleen inflammation, Th1 immune response, as well as injury to the kidney and liver, and ameliorated the abnormal glucose metabolism in both preventive and curative models. In the in vitro model, rutin inhibited pro-inflammatory cytokines secreted by 3T3-L1 preadipocytes and differentiation of preadipocytes. The results suggest that rutin supplementation improved metabolic syndrome features, inflammation and Th1/Th2 balance under metabolic syndrome stress, possibly via inhibiting inflammation and differentiation of adipocytes.

Topic Category 農業暨自然資源學院 > 食品暨應用生物科技學系所
生物農學 > 生物科學
  1. 闕維涵。2010。黃聯素補充對第1型糖尿病非肥胖性小鼠免疫調節作用及其保護
  2. 陳佳琪。2010。攝食苦蕎麥對雞卵白蛋白致敏之氣喘模式小鼠免疫調節功能的影
  3. extracellular superoxide dismutase during adipose differentiation in 3T3-L1
  4. cells. Redox Rep 14, 34-40.
  5. Arulmozhi, D.K., Kurian, R., Bodhankar, S.L., and Veeranjaneyulu, A. (2008).
  6. diabetes. J Pharm Pharmacol 60, 1167-1173.
  7. adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7,
  8. Expression of specific mRNAs during adipose differentiation: identification of
  9. Bjorntorp, P., Berchtold, P., and Tibblin, G. (1971). Insulin secretion in relation to
  10. men. Eur J Endocrinol 148, 535-542.
  11. Speizer, F.E., and Manson, J.E. (1997). Body fat distribution and risk of
  12. non-insulin-dependent diabetes mellitus in women. The Nurses' Health Study.
  13. Am J Epidemiol 145, 614-619.
  14. Chandran, M., Phillips, S.A., Ciaraldi, T., and Henry, R.R. (2003). Adiponectin: more
  15. than just another fat cell hormone? Diabetes Care 26, 2442-2450.
  16. Chen, S., Gong, J., Liu, F., and Mohammed, U. (2000). Naturally occurring
  17. polyphenolic antioxidants modulate IgE-mediated mast cell activation.
  18. Immunology 100, 471-480.
  19. inflammation-related genes in white adipose tissue of obese subjects. FASEB J
  20. Compher, C., and Badellino, K.O. (2008). Obesity and inflammation: lessons from
  21. bariatric surgery. JPEN J Parenter Enteral Nutr 32, 645-647.
  22. Coppack, S.W. (2001). Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc
  23. disease in parasitic infections, asthma and reproductive biology. J Reprod
  24. Immunol 57, 255-272.
  25. buckwheat (Fagopyrum tataricum Gaertn.) as a source of dietary rutin and
  26. quercitrin. J Agric Food Chem 51, 6452-6455.
  27. and adipocytes from visceral and subcutaneous abdominal adipose tissues of
  28. obese humans. Endocrinology 145, 2273-2282.
  29. J.F., and Fernandes Junior, A. (2010). Influence of rutin treatment on
  30. Ferrero-Miliani, L., Nielsen, O.H., Andersen, P.S., and Girardin, S.E. (2007). Chronic
  31. inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation.
  32. Clin Exp Immunol 147, 227-235.
  33. Galli, S.J., Maurer, M., and Lantz, C.S. (1999). Mast cells as sentinels of innate
  34. immunity. Curr Opin Immunol 11, 53-59.
  35. Chemokines control fat accumulation and leptin secretion by cultured human
  36. adipocytes. Mol Cell Endocrinol 175, 81-92.
  37. linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol
  38. obtained from tartary buckwheat. Int J Mol Sci 11, 5201-5211.
  39. Gustafson, B. (2010). Adipose tissue, inflammation and atherosclerosis. J Atheroscler
  40. Thromb 17, 332-341.
  41. Gustafson, B., Hammarstedt, A., Andersson, C.X., and Smith, U. (2007). Inflamed
  42. adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis.
  43. Arterioscler Thromb Vasc Biol 27, 2276-2283.
  44. Gustafson, B., and Smith, U. (2006). Cytokines promote Wnt signaling and
  45. Han, Y. (2009). Rutin has therapeutic effect on septic arthritis caused by Candida
  46. albicans. Int Immunopharmacol 9, 207-211.
  47. preadipocytes than in adipocytes of 3T3-L1 cells and C57BL/6J and ob/ob mice.
  48. J Nutr 134, 2673-2677.
  49. subsets affect patterns of injury and outcomes in glomerulonephritis. Kidney Int
  50. Holt, R.I. (2005). International Diabetes Federation re-defines the metabolic syndrome.
  51. Diabetes Obes Metab 7, 618-620.
  52. Hotamisligil, G.S., Arner, P., Caro, J.F., Atkinson, R.L., and Spiegelman, B.M. (1995).
  53. Increased adipose tissue expression of tumor necrosis factor-alpha in human
  54. obesity and insulin resistance. J Clin Invest 95, 2409-2415.
  55. o-coumaric acid ameliorate obesity induced by high-fat diet in rats. J Agric Food
  56. Hsu, C.L., and Yen, G.C. (2007). Effects of flavonoids and phenolic acids on the
  57. preadipocyte differentiation in human abdominal obesity: role of Wnt, tumor
  58. necrosis factor-alpha, and inflammation. Diabetes 58, 1550-1557.
  59. flavonol-rich diet on select cardiovascular parameters in a Golden Syrian
  60. Kershaw, E.E., and Flier, J.S. (2004). Adipose tissue as an endocrine organ. J Clin
  61. Endocrinol Metab 89, 2548-2556.
  62. health and disease. Altern Med Rev 8, 223-246.
  63. selectively improves hepatic insulin action in obesity. Endocrinology 146,
  64. Kupecz, D. (1995). Metformin: an antihyperglycemic drug for non-insulin-dependent
  65. diabetes mellitus. Nurse Pract 20, 70-72.
  66. and Fukushima, M. (2007). Tartary buckwheat sprout powder lowers plasma
  67. its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental
  68. Pharmacol 69, 395-406.
  69. formation by decreasing reactive oxygen species and TNF-alpha by inhibiting
  70. activation of NF-kappaB. Exp Mol Med 40, 52-58.
  71. switch in adipose tissue macrophage polarization. J Clin Invest 117, 175-184.
  72. I.M., and Rodrigues, A.L. (2008). Antidepressant-like effect of rutin isolated
  73. inflammation and metabolic syndrome. Mol Cell Endocrinol 314, 1-16.
  74. Medzhitov, R., and Janeway, C., Jr. (2000). Innate immunity. N Engl J Med 343,
  75. actions of pro-inflammatory and anti-inflammatory agents: key role for
  76. Miranda, P.J., DeFronzo, R.A., Califf, R.M., and Guyton, J.R. (2005). Metabolic
  77. syndrome: definition, pathophysiology, and mechanisms. Am Heart J 149,
  78. increases AMP-activated protein kinase activity in skeletal muscle of subjects
  79. of opioid system activity for anticonvulsant activities of rutin in mice. Clin Nutr.
  80. obesity is an independent risk factor for chronic heart failure in older people. J
  81. Am Geriatr Soc 54, 413-420.
  82. The metabolism of isoforms of human adiponectin: studies in human subjects
  83. Pepys, M.B., and Hirschfield, G.M. (2003). C-reactive protein: a critical update. J Clin
  84. Petersen, A.M., and Pedersen, B.K. (2005). The anti-inflammatory effect of exercise. J
  85. Appl Physiol 98, 1154-1162.
  86. Phillips, S.A., and Kung, J.T. (2010). Mechanisms of adiponectin regulation and use as
  87. a pharmacological target. Curr Opin Pharmacol 10, 676-683.
  88. protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA
  89. Reaven, G.M. (1988). Banting lecture 1988. Role of insulin resistance in human
  90. disease. Diabetes 37, 1595-1607.
  91. micro-inflammatory response in the metabolic syndrome: a cross sectional study.
  92. J Inflamm (Lond) 7, 35.
  93. Gower Medical Pub.).
  94. Immunotoxicol 29, 271-285.
  95. relationship between waist circumference, morbidity and mortality depend on
  96. Biol Chem 278, 45777-45784.
  97. Ruan, H., and Lodish, H.F. (2003). Insulin resistance in adipose tissue: direct and
  98. indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev 14,
  99. immediate target of tumor necrosis factor-alpha: implications for insulin
  100. Russell, T.R., and Ho, R. (1976). Conversion of 3T3 fibroblasts into adipose cells:
  101. xanthine. Proc Natl Acad Sci U S A 73, 4516-4520.
  102. Davis, R.J. (2008). A stress signaling pathway in adipose tissue regulates hepatic
  103. effects of high fat and sucrose diets on obesity and lymphocyte proliferation in
  104. mice. J Nutr Health Aging 13, 602-606.
  105. Scherer, P.E. (2006). Adipose tissue: from lipid storage compartment to endocrine
  106. organ. Diabetes 55, 1537-1545.
  107. weight and glucose tolerance in glucagon-like peptide-1 receptor -/- mice.
  108. Endocrinology 139, 3127-3132.
  109. and quantitative analysis of nonneoplastic lesions in toxicology studies. Toxicol
  110. Pathol 30, 93-96.
  111. Singh, V.K., Mehrotra, S., and Agarwal, S.S. (1999). The paradigm of Th1 and Th2
  112. cytokines: its relevance to autoimmunity and allergy. Immunol Res 20, 147-161.
  113. differentiation implicate interleukin-6 as a paracrine regulator. Obes Res 12,
  114. of fat cell turnover in humans. Nature 453, 783-787.
  115. Evidence for the involvement of interleukin 10 in the differential deactivation of
  116. (2010). T-cell recruitment and Th1 polarization in adipose tissue during
  117. and macrophages aggravates inflammatory changes: role of free fatty acids and
  118. tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 25, 2062-2068.
  119. Tisch, R., and McDevitt, H. (1996). Insulin-dependent diabetes mellitus. Cell 85,
  120. Wajchenberg, B.L. (2000). Subcutaneous and visceral adipose tissue: their relation to
  121. the metabolic syndrome. Endocr Rev 21, 697-738.
  122. of abdominal adiposity and overall obesity in predicting risk of type 2 diabetes
  123. among men. Am J Clin Nutr 81, 555-563.
  124. A.W., Jr. (2003). Obesity is associated with macrophage accumulation in adipose
  125. tissue. J Clin Invest 112, 1796-1808.
  126. subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II
  127. diabetes independent of insulin resistance. Diabetologia 43, 1498-1506.
  128. Wisse, B.E. (2004). The inflammatory syndrome: the role of adipose tissue cytokines in
  129. Woollard, K.J., and Geissmann, F. (2010). Monocytes in atherosclerosis: subsets and
  130. functions. Nat Rev Cardiol 7, 77-86.
  131. H. (2009). Children's immunology, what can we learn from animal studies (2):
  132. receptor 2 affects 3T3-L1 preadipocyte differentiation. Mol Cell Endocrinol 311,
  133. Yao, Y., Shan, F., Bian, J., Chen, F., Wang, M., and Ren, G. (2008).
  134. Yudkin, J.S., Kumari, M., Humphries, S.E., and Mohamed-Ali, V. (2000). Inflammation,
  135. obesity, stress and coronary heart disease: is interleukin-6 the link?
  136. Atherosclerosis 148, 209-214.
  137. http://www.bhp.doh.gov.tw/bhpnet/portal/Them_Show.aspx?Subject=200712250023&Class=2&No=200712250119 行政院衛生署國民健康局於94/01/25公告之台灣代謝症
  138. 苗明三。1997。實驗動物和動物實驗技術。中國中醫藥出版社。P143。
  139. 初代胰島細胞機制之研究。國立中興大學食品暨應用生物科技學系碩士論
  140. 文。
  141. 響。國立中興大學食品暨應用生物科技學系碩士論文。
  142. Adachi, T., Toishi, T., Wu, H., Kamiya, T., and Hara, H. (2009). Expression of
  143. Metabolic effects of various antidiabetic and hypolipidaemic agents on a
  144. high-fat diet and multiple low-dose streptozocin (MLDS) mouse model of
  145. Berg, A.H., Combs, T.P., Du, X., Brownlee, M., and Scherer, P.E. (2001). The
  146. 947-953.
  147. Bernlohr, D.A., Angus, C.W., Lane, M.D., Bolanowski, M.A., and Kelly, T.J., Jr. (1984).
  148. an mRNA encoding a homologue of myelin P2 protein. Proc Natl Acad Sci U S
  149. A 81, 5468-5472.
  150. adipose tissue in men. Diabetes 20, 65-70.
  151. Bruun, J.M., Verdich, C., Toubro, S., Astrup, A., and Richelsen, B. (2003). Association
  152. between measures of insulin sensitivity and circulating levels of interleukin-8,
  153. interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese
  154. Carey, V.J., Walters, E.E., Colditz, G.A., Solomon, C.G., Willett, W.C., Rosner, B.A.,
  155. Chang, H.H., Chen, C.S., and Lin, J.Y. (2009). Dietary perilla oil lowers serum lipids
  156. and ovalbumin-specific IgG1, but increases total IgE levels in
  157. ovalbumin-challenged mice. Food Chem Toxicol 47, 848-854.
  158. Choi, I., Park, Y., Choi, H., and Lee, E.H. (2006). Anti-adipogenic activity of rutin in
  159. 3T3-L1 cells and mice fed with high-fat diet. Biofactors 26, 273-281.
  160. Clement, K., Viguerie, N., Poitou, C., Carette, C., Pelloux, V., Curat, C.A., Sicard, A.,
  161. Rome, S., Benis, A., Zucker, J.D., et al. (2004). Weight loss regulates
  162. 18, 1657-1669.
  163. 60, 349-356.
  164. Cruvinel Wde, M., Mesquita, D., Jr., Araujo, J.A., Catelan, T.T., de Souza, A.W., da
  165. Silva, N.P., and Andrade, L.E. (2010). Immune system - part I. Fundamentals of
  166. innate immunity with emphasis on molecular and cellular mechanisms of
  167. inflammatory response. Rev Bras Reumatol 50, 434-461.
  168. Dent, L.A. (2002). For better or worse: common determinants influencing health and
  169. Erlund, I., Kosonen, T., Alfthan, G., Maenpaa, J., Perttunen, K., Kenraali, J.,
  170. Parantainen, J., and Aro, A. (2000). Pharmacokinetics of quercetin from
  171. quercetin aglycone and rutin in healthy volunteers. Eur J Clin Pharmacol 56,
  172. 545-553.
  173. Fabjan, N., Rode, J., Kosir, I.J., Wang, Z., Zhang, Z., and Kreft, I. (2003). Tartary
  174. Fain, J.N., Madan, A.K., Hiler, M.L., Cheema, P., and Bahouth, S.W. (2004).
  175. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix,
  176. Fernandes, A.A., Novelli, E.L., Okoshi, K., Okoshi, M.P., Di Muzio, B.P., Guimaraes,
  177. biochemical alterations in experimental diabetes. Biomed Pharmacother 64,
  178. 214-219.
  179. Friedewald, W.T., Levy, R.I., and Fredrickson, D.S. (1972). Estimation of the
  180. concentration of low-density lipoprotein cholesterol in plasma, without use of
  181. the preparative ultracentrifuge. Clin Chem 18, 499-502.
  182. Gerhardt, C.C., Romero, I.A., Cancello, R., Camoin, L., and Strosberg, A.D. (2001).
  183. Guilherme, A., Virbasius, J.V., Puri, V., and Czech, M.P. (2008). Adipocyte dysfunctions
  184. 9, 367-377.
  185. Guo, X., Zhu, K., Zhang, H., and Yao, H. (2010). Anti-tumor activity of a novel protein
  186. inflammation and impair the normal differentiation and lipid accumulation in
  187. 3T3-L1 preadipocytes. J Biol Chem 281, 9507-9516.
  188. Harkins, J.M., Moustaid-Moussa, N., Chung, Y.J., Penner, K.M., Pestka, J.J., North,
  189. C.M., and Claycombe, K.J. (2004). Expression of interleukin-6 is greater in
  190. Holdsworth, S.R., Kitching, A.R., and Tipping, P.G. (1999). Th1 and Th2 T helper cell
  191. 55, 1198-1216.
  192. Hopps, E., Canino, B., and Caimi, G. (2011). Effects of exercise on inflammation
  193. markers in type 2 diabetic subjects. Acta Diabetol.
  194. Hsu, C.L., Wu, C.H., Huang, S.L., and Yen, G.C. (2009). Phenolic compounds rutin and
  195. Chem 57, 425-431.
  196. inhibition of adipogenesis in 3T3-L1 adipocytes. J Agric Food Chem 55,
  197. 8404-8410.
  198. Isakson, P., Hammarstedt, A., Gustafson, B., and Smith, U. (2009). Impaired
  199. Kalgaonkar, S., Gross, H.B., Yokoyama, W., and Keen, C.L. (2010). Effects of a
  200. hamster model. J Med Food 13, 108-115.
  201. Kidd, P. (2003). Th1/Th2 balance: the hypothesis, its limitations, and implications for
  202. Klover, P.J., Clementi, A.H., and Mooney, R.A. (2005). Interleukin-6 depletion
  203. 3417-3427.
  204. Kuwabara, T., Han, K.H., Hashimoto, N., Yamauchi, H., Shimada, K., Sekikawa, M.,
  205. cholesterol level in rats. J Nutr Sci Vitaminol (Tokyo) 53, 501-507.
  206. Kwon, K.H., Murakami, A., Tanaka, T., and Ohigashi, H. (2005). Dietary rutin, but not
  207. colitis in mice: attenuation of pro-inflammatory gene expression. Biochem
  208. Kyung, T.W., Lee, J.E., Shin, H.H., and Choi, H.S. (2008). Rutin inhibits osteoclast
  209. Lang, H.F., Chou, C.Y., Sheu, H.H., and Lin, J.Y. (2011). Weight loss increased serum
  210. adiponectin but decreased lipid levels in obese subjects whose body mass index
  211. was lower than 30 kg/m2. Nutr Res 2011;31;378-86
  212. Li, F.Y., Cheng, K.K., Lam, K.S., Vanhoutte, P.M., and Xu, A. (2010a). Cross-talk
  213. between adipose tissue and vasculature: role of adiponectin. Acta Physiol (Oxf).
  214. Li, R., Lau, W.B., and Ma, X.L. (2010b). Adiponectin resistance and vascular
  215. dysfunction in the hyperlipidemic state. Acta Pharmacol Sin 31, 1258-1266.
  216. Lumeng, C.N., Bodzin, J.L., and Saltiel, A.R. (2007). Obesity induces a phenotypic
  217. Machado, D.G., Bettio, L.E., Cunha, M.P., Santos, A.R., Pizzolatti, M.G., Brighente,
  218. from the ethanolic extract from Schinus molle L. in mice: evidence for the
  219. involvement of the serotonergic and noradrenergic systems. Eur J Pharmacol
  220. 587, 163-168.
  221. Maury, E., and Brichard, S.M. (2010). Adipokine dysregulation, adipose tissue
  222. 338-344.
  223. Mesquita Junior, D., Araujo, J.A., Catelan, T.T., Souza, A.W., Cruvinel Wde, M.,
  224. Andrade, L.E., and Silva, N.P. (2010). Immune system - part II: basis of the
  225. immunological response mediated by T and B lymphocytes. Rev Bras Reumatol
  226. 50, 552-580.
  227. Michlewska, S., Dransfield, I., Megson, I.L., and Rossi, A.G. (2009). Macrophage
  228. phagocytosis of apoptotic neutrophils is critically regulated by the opposing
  229. TNF-alpha. FASEB J 23, 844-854.
  230. 33-45.
  231. Murphy, K.P., Travers, P., Walport, M., and Janeway, C. (2008). Janeway's
  232. immunobiology, 7th edn (New York, Garland Science).
  233. Musi, N., Hirshman, M.F., Nygren, J., Svanfeldt, M., Bavenholm, P., Rooyackers, O.,
  234. Zhou, G., Williamson, J.M., Ljunqvist, O., Efendic, S., et al. (2002). Metformin
  235. with type 2 diabetes. Diabetes 51, 2074-2081.
  236. Nassiri-Asl, M., Zamansoltani, F., Javadi, A., and Mahyar, A. (2009). The possible role
  237. Nicklas, B.J., Cesari, M., Penninx, B.W., Kritchevsky, S.B., Ding, J., Newman, A.,
  238. Kitzman, D.W., Kanaya, A.M., Pahor, M., and Harris, T.B. (2006). Abdominal
  239. Ouchi, N., Kihara, S., Arita, Y., Okamoto, Y., Maeda, K., Kuriyama, H., Hotta, K.,
  240. Nishida, M., Takahashi, M., Muraguchi, M., et al. (2000). Adiponectin, an
  241. adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling
  242. through a cAMP-dependent pathway. Circulation 102, 1296-1301.
  243. Peake, P.W., Kriketos, A.D., Campbell, L.V., Shen, Y., and Charlesworth, J.A. (2005).
  244. and in experimental animals. Eur J Endocrinol 153, 409-417.
  245. Invest 111, 1805-1812.
  246. Poulain-Godefroy, O., and Froguel, P. (2007). Preadipocyte response and impairment of
  247. differentiation in an inflammatory environment. Biochem Biophys Res Commun
  248. 356, 662-667.
  249. Pradhan, A.D., Manson, J.E., Rifai, N., Buring, J.E., and Ridker, P.M. (2001). C-reactive
  250. 286, 327-334.
  251. Prins, J.B., Niesler, C.U., Winterford, C.M., Bright, N.A., Siddle, K., O'Rahilly, S.,
  252. Walker, N.I., and Cameron, D.P. (1997). Tumor necrosis factor-alpha induces
  253. apoptosis of human adipose cells. Diabetes 46, 1939-1944.
  254. Rogowski, O., Shapira, I., Bassat, O.K., Chundadze, T., Finn, T., Berliner, S., and
  255. Steinvil, A. (2010). Waist circumference as the predominant contributor to the
  256. Roitt, I.M., Brostoff, J., and Male, D.K. (1989). Immunology, 2nd edn (New York,
  257. Roitt I, Brostoff J, and Male, D.K. (1998). Immunology, Fifth Edition. Philadelphia:
  258. Mosby.
  259. Roseghini, R., Rocha, D.S., Clarencio, J., Costa, S.L., Costa, M.F., Tardy, M.,
  260. Nascimento, R., Schaer, R., Velozo, E., Meyer, R., et al. (2007). Flavonoid rutin
  261. alters the viability and function of mitogen-stimulated splenocytes and
  262. thymocytes compared with non stimulated cells. Immunopharmacol
  263. Ross, R., Berentzen, T., Bradshaw, A.J., Janssen, I., Kahn, H.S., Katzmarzyk, P.T., Kuk,
  264. J.L., Seidell, J.C., Snijder, M.B., Sorensen, T.I., et al. (2008). Does the
  265. measurement protocol for waist circumference? Obes Rev 9, 312-325.
  266. Rotter, V., Nagaev, I., and Smith, U. (2003). Interleukin-6 (IL-6) induces insulin
  267. resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis
  268. factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J
  269. 447-455.
  270. Ruan, H., Miles, P.D., Ladd, C.M., Ross, K., Golub, T.R., Olefsky, J.M., and Lodish,
  271. H.F. (2002). Profiling gene transcription in vivo reveals adipose tissue as an
  272. resistance. Diabetes 51, 3176-3188.
  273. triggering of differentiation by prostaglandin F2alpha and 1-methyl-3-isobutyl
  274. Sabio, G., Das, M., Mora, A., Zhang, Z., Jun, J.Y., Ko, H.J., Barrett, T., Kim, J.K., and
  275. insulin resistance. Science 322, 1539-1543.
  276. Sato Mito, N., Suzui, M., Yoshino, H., Kaburagi, T., and Sato, K. (2009). Long term
  277. Scrocchi, L.A., and Drucker, D.J. (1998). Effects of aging and a high fat diet on body
  278. Sen, A., Lea-Currie, Y.R., Sujkowska, D., Franklin, D.M., Wilkison, W.O., Halvorsen,
  279. Y.D., and Gimble, J.M. (2001). Adipogenic potential of human adipose derived
  280. stromal cells from multiple donors is heterogeneous. J Cell Biochem 81,
  281. 312-319.
  282. Shackelford, C., Long, G., Wolf, J., Okerberg, C., and Herbert, R. (2002). Qualitative
  283. Sopasakis, V.R., Sandqvist, M., Gustafson, B., Hammarstedt, A., Schmelz, M., Yang,
  284. X., Jansson, P.A., and Smith, U. (2004). High local concentrations and effects on
  285. 454-460.
  286. Spalding, K.L., Arner, E., Westermark, P.O., Bernard, S., Buchholz, B.A., Bergmann,
  287. O., Blomqvist, L., Hoffstedt, J., Naslund, E., Britton, T., et al. (2008). Dynamics
  288. Stanely Mainzen Prince, P., and Kannan, N.K. (2006). Protective effect of rutin on
  289. lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins in
  290. streptozotocin-induced diabetic rats. J Pharm Pharmacol 58, 1373-1383.
  291. Strassmann, G., Patil-Koota, V., Finkelman, F., Fong, M., and Kambayashi, T. (1994).
  292. murine peritoneal macrophages by prostaglandin E2. J Exp Med 180,
  293. 2365-2370.
  294. Strissel, K.J., DeFuria, J., Shaul, M.E., Bennett, G., Greenberg, A.S., and Obin, M.S.
  295. diet-induced obesity in C57BL/6 mice. Obesity (Silver Spring) 18, 1918-1925.
  296. Suganami, T., Nishida, J., and Ogawa, Y. (2005). A paracrine loop between adipocytes
  297. 291-297.
  298. Travers, P., Walport, M., and Janeway's, C. (2005). Immuno Biology: the immune
  299. system and disease. 6th edn. Garland Science Publishing.
  300. Wang, Y., Rimm, E.B., Stampfer, M.J., Willett, W.C., and Hu, F.B. (2005). Comparison
  301. Weisberg, S.P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R.L., and Ferrante,
  302. Weyer, C., Foley, J.E., Bogardus, C., Tataranni, P.A., and Pratley, R.E. (2000). Enlarged
  303. metabolic disorders linked to obesity. J Am Soc Nephrol 15, 2792-2800.
  304. Yamamoto, S., Tin Tin Win, S., Yoshida, Y., Kunugita, N., Arashidani, K., and Fujimaki,
  305. Modulation of systemic Th1/Th2 immune response in infant mice after prenatal
  306. exposure to low-level toluene and toll-like receptor (TLR) 2 ligand. J Toxicol
  307. Sci 34 Suppl 2, SP341-348.
  308. Yang, J., Yuan, C., Wei, L., Yi, F., and Song, F. (2009). Melanin-concentrating hormone
  309. 11-17.
  310. D-chiro-inositol-enriched tartary buckwheat bran extract lowers the blood
  311. glucose level in KK-Ay mice. J Agric Food Chem 56, 10027-10031.
  312. http://www.lupusresearchinstitute.org/downloads/immune.pdf. (搜尋日期:2011/05/05)
  313. http://www.newworldencyclopedia.org/entry/Immune_system#Innate_immune_system
  314. (搜尋日期:2011/05/05)
  315. http://en.wikipedia.org/wiki/Immune_system (搜尋日期:2011/05/05)
  316. 候群現況(搜尋日期:2011/05/05)
  317. http://www.doh.gov.tw/CHT2006/DM/DM2_2_p02.aspx?class_no=440&now_fod_list_no=11962&level_no=4&doc_no=81294 行政院衛生署民國99年死因結果摘要表
  318. (搜尋日期:2011/07/23)