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肥胖發炎與糖尿病

肥胖發炎與糖尿病. 國防醫學院生理學研究所 謝 博軒教授兼所長. 成人肥胖定義及分類. 定義 肥胖是指體脂肪囤積過多 評估方式 身體質量指數 (body mass index, BMI) = Body weight (kg) / height 2 (m 2 ) 與體脂肪有高度相關性 BMI 易造成分類錯誤之個案 ， 運動員 ( 高估 ) 、 少女和年長者 ( 低估 ) 合併腰圍和 BMI 測量 ， 能減少錯誤分類 相同 BMI ≠ 相同體脂率 ( 男 < 女 ， 年長 > 年輕 ). “Thrifty gene” hypothesis.

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肥胖發炎與糖尿病

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  1. 肥胖發炎與糖尿病 國防醫學院生理學研究所 謝博軒教授兼所長

  2. 成人肥胖定義及分類 • 定義 肥胖是指體脂肪囤積過多 • 評估方式 • 身體質量指數 (body mass index, BMI) = Body weight (kg) / height2 (m2) 與體脂肪有高度相關性 • BMI 易造成分類錯誤之個案，運動員(高估) 、 少女和年長者(低估) • 合併腰圍和 BMI 測量，能減少錯誤分類 • 相同BMI ≠ 相同體脂率(男<女，年長>年輕)

  3. “Thrifty gene” hypothesis

  4. 肥胖是全球性的問題

  5. 台灣成人過重與肥胖的盛行率 The prevalence of overweight (BMI>24 kg.m-2) and obesity (BMI>27 kg.m-2) in Taiwanese adults categorized by gender and calendar years (Obesity review 2008)

  6. 肥胖臨床併發症

  7. 肥胖對死亡率之影響

  8. 肥胖與糖尿病

  9. 肥胖與糖尿病的盛行率

  10. 肥胖發炎與糖尿病

  11. 免疫機制與營養狀態之關聯性

  12. 肥胖發炎與疾病的關聯性

  13. 肥胖和脂肪組織發炎

  14. 脂肪組織發炎和免疫細胞浸潤

  15. 肥胖組織發炎與胰島素抗性 Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance J Clin Invest. 112(12):1821-30 (2003). Obesity is associated with macrophage accumulation in adipose tissue J. Clin. Invest. 112:1796–1808 (2003). Crown-like structure

  16. 脂肪細胞與巨噬細胞在代謝與免疫反應的 共同機轉

  17. 肥胖誘發的發炎反應與胰島素抗性之關聯性

  18. Adaptive immune system Arterioscler Thromb Vasc Biol. 2008;28:1211-1213

  19. T-cell and RANTES Circulation. 2007;115:1029-1038 International Journal of Obesity (2008) 32, 451–463

  20. 後天免疫系統對脂肪組織發炎的影響 15 (8): 914-921, 2009 15 (8): 930-939, 2009

  21. Adipose tissue cell interactions during High-fat diet induced inflammation CIITA, class II transactivator, the master transcriptional regulator of the MHCII pathway MHCII, major histocompatibility complex II Cell Metabolism 17:411-422, 2013

  22. Obesity and Adipose Tissue Inflammation

  23. 肥胖造成發炎反應機轉及系統性胰島素抗性產生關係肥胖造成發炎反應機轉及系統性胰島素抗性產生關係

  24. 抗發炎性藥物在肥胖治療上的開發與應用

  25. Obesity and Inflammation

  26. 抗發炎性藥物在肥胖誘發胰島素抗性和心血管疾病的治療潛力抗發炎性藥物在肥胖誘發胰島素抗性和心血管疾病的治療潛力 ■ Yuan MS et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IKKβ. Science 2001 31:1673-1677

  27. ■Hirosumi J et al. A central role for JNK in obesity and insulin resistance. Nature 2002 420:333-337 JNK, c-jun amino-terminal kinase

  28. The Importance of Adipose Cyclooxygenase 2 activation in the Development of Obesity-induced Insulin Resistance and Fatty Liver Circulation 2004;109;1729-1734

  29. COX 2 Activation and Obesity-induced adipose inflammation Obesity COX-2 inhibitor COX-2 ↑ MCP-1↑ MCP-1↓ TNF-α、MCP-1 Improved insulin sensitivity

  30. COX 2 Activation and Obesity-associated suppression In adipocyte differentiation Adipose tissue inflammation Pro-inflamatory cytokines and chemokines TNF-α, MCP-1 Adipocyte hypertrophy COX-2 inhibitor COX-2 COX-2 Differentiation

  31. European Journal of Clinical Investigation 2008 38 (11): 812-819. Obesity 2009 17(6):1150-1157 European J Clinical Investigation 2010:40(2):164-171 Life Science 2011:89:107-114

  32. 肥胖與免疫治療

  33. ArteriosclerThrombVasc Biol. 2008;28:1211-1213

  34. Nature Medince 15(8):921-930, 2009 Diet-induced obese mice ob/ob obese mice CD3-specific antibody 10 ug/d x 5 Lasting > 4 months T helper type 1 (TH1) cells T helper type 2 (TH2) cells

  35. 結論 肥胖發炎在第二型糖尿病的發展上扮演重要角色 肥胖發炎主要來自於脂肪組織發炎 先天(Innate immunity)和後天免疫(adaptive immunity)系統在肥胖造成脂肪組織發炎中均扮演重要角色 特定抗發炎性藥物具有改善肥胖發炎和胰島素抗性的潛力 免疫治療具治療肥胖相關第二型糖尿病的潛力

  36. 身體對營養過剩與病原體感染之反應系統之異同身體對營養過剩與病原體感染之反應系統之異同

  37. 肥胖病人都需要接受治療嗎?

  38. 肥胖治療策略 減重(飲食運動) 抗發炎性藥物?? 脂肪組織無發炎 脂肪組織發炎 正常生理功能 系統性胰島素抗性 心血管疾病 (需積極治療族群)

  39. Thank you for your attention

  40. 展望未來Where will we be tomorrow? • 肥胖盛行率往後可能會持續升高 • 學者依目前肥胖增加趨勢，預計到2030年每個人都會變成肥胖

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