肥胖是身體累積過多脂肪組織的狀態，這些過多的脂肪組織是導致代謝異常及心血管疾病的危險因子，其中很常引起的就是高血壓。近年來，國人十大死亡因前三名分別是惡性腫瘤、心臟病和腦血管疾病，和高血壓直接有關或密切相關的疾病佔了三分之二，由此可見高血壓對於國民健康所造成的威脅。
根據研究，AGT基因或angiotensinogen(AGT基因之產物)是體內主要控制血壓的物質，血壓較高、體型較肥胖者血液中angiotensinogen會較多。因此我們利用lentivirus攜帶shRNA，於脂肪先驅細胞細胞株表達，將Agt knockdown，來探究Agt基因於脂肪細胞分化所扮演的角色。結果發現：當Agt基因被抑制表達後，新生脂肪細胞比例會降低。此外，AngI、AngII是angiotensinogen被分解後調控血壓的胜�忖軉q。但外加AngI、AngII於Agt基因被抑制的前驅脂肪細胞並不會讓細胞有回復分化能力的狀況。若是直接送入去掉angiotensin片段的AGT基因質體，於Agt基因被抑制的前驅脂肪細胞，則細胞分化能力可被回復，新生脂肪的生成率會提高。這些實驗都顯示 AngI、AngII不是angiotensinogen影響脂肪分化的部分。本實驗進一步尋找AGT基因調控脂肪生成的部分，目前認為AGT基因會生成angiotensinogen後段的絲氨酸蛋白�“磻豯硎c(serpin domain)部分也不是影響脂肪新生的片段。

Obesity is a state of excessive fat accumulation. Obesity is associated with increased risk of other metabolic disorders and cardiovascular diseases. Hypertension is among the abnormalities associated with obesity.of The top three of the ten leading causes of death in Taiwan were carcinoma, heart diseases and cerebrovascular diseases. Hypertension is a predisposing factor of the later two. The implication of hypertension on public health is clear.
Angiotensinogen, the product of AGT gene, is the main determinant of blood pressure. Obese or hypertensive individuals have more angiotensinogen in their blood. . In order to understand the role of the Agt gene in adipocyte formation, we knocked down the Agt gene using the lentivirus expressing shRNA targeting Agt. Adipogenesis was inhibited when Agt was knocked down.Angiotensinogen increases blood pressure by generating decapeptide AngI and octapeptide AngII. AngI and AngII could not restore the adipogenicity in Agt knockdown preadipocyte. Over-expressing human AGT cDNA lacking the sequence coding AgnI and AgnII in Agt knockdown 3T3-L1 preadipocytes restored adipogenicity. These experiments showed that AngI and AngII were not required for fat differentiation. The serpin domain of angiotensinogen alone was also not enough to support adipogenesis.

摘要(中文）................................................................. II
摘要（英文）................................................................III
ㄧ.前言................................................................... ...1
二.材料與方法................................................................ 8
三.結果..................................................................... 23
四.討論..................................................................... 27
五.文獻參考..................................................................29
六.結果圖....................................................................31
附圖.........................................................................38

Brenner & Rector's The Kidney, 7th ed. Saunders 2004; pp.2118-2119.
Carretero OA, Oparil S. Essential hypertension. Part I: definition and etiology.Circulation 2000; 101 (3): 329–35.
Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42 (6): 1206–52.
Elberg, G., Gimble, J. M., and Tsai, S. Y. Modulation of the murine peroxisome proliferator-activated receptor gamma 2 promoter activity by CCAAT/enhancer-binding proteins. J Biol Chem 275 2000; 27815-27822.
Engeli S, Bohnke J, Gorzelniak K et al. Weight loss and the renin–angiotensin–aldosterone system. Hypertension 2005; 45: 356–362
Eriksson, J. W., Smith, U., Waagstein, F., Wysocki, M., and Jansson, P. A. (). Glucose turnover and adipose tissue lipolysis are insulin-resistant in healthy relatives of type 2 diabetes patients: is cellular insulin resistance a secondary phenomenon? Diabetes 48 1999; 1572-1578.
Faust, I. M., Johnson, P. R., Stern, J. S., and Hirsch, J. Diet-induced adipocyte number increase in adult rats: a new model of obesity. Am J Physiol 235 1978; E279-286.
Freedman DS, Khan LK, Serdula MK, Galuska DA, Dietz WH. Trends and correlates of class 3 obesity in the United States from 1990 through 2000. JAMA 2002; 288: 1758–61
Fujino T, Nakagawa N, Yuhki K, et al. Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP. J. Clin. Invest. 2004; 114 (6): 805–12.
Green, H. and Meuth, M. An established pre-adipose cell line and its differentiation in culture. Cell 1974; 3(2):127-133.
Guyton & Hall. Textbook of Medical Physiology (7th ed.).Elsevier-Saunders. 2005;pp. 220.
Hall JE, Brands MW, Dixon WN, et al. Obesity-induced hypertension. Renal function and systemic hemodynamics. Hypertension. 1993;22:292-299.
Hall JE, Zappe DH, Alonso-Galicia M, et al. Mechanisms of obesity-induced hypertension. News Physiol Sci. 1996;11:255-261.
Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365: 217–223
Krause RM, Winston M, Fletcher BJ, Grundy SM. Obesity. Impact on cardiovascular disease. Circulation 1998; 98: 1472–1476
Nguyen G, Delarue F, Burckl�� C, Bouzhir L, Giller T, Sraer JD. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin..J. Clin. Invest 2002;109 (11): 1417–27.
Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension.Ann. Intern. Med. 2003;139 (9): 761–76.
Pratt RE, Flynn JA, Hobart PM, Paul M, Dzau VJ. Different secretory pathways of renin from mouse cells transfected with the human renin gene. J. Biol. Chem. 1988;263 (7): 3137–41.
Thompson D, Edelsberg J, Colditz GA, Bird AP, Oster G. Lifetime health and economic consequences of obesity. Archives of Internal Medicine 1999; 159: 2177–83