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研究生:李弘元
研究生(外文):Hung-Yuan Li
論文名稱:血管附著蛋白-1與肥胖的關係
論文名稱(外文):The Association of Vascular Adhesion Protein-1 and Obesity
指導教授:莊立民莊立民引用關係
指導教授(外文):Lee-Ming Chuang
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:60
中文關鍵詞:肥胖血管附著蛋白-1脂肪分佈血壓
外文關鍵詞:vascular adhesion protein-1central obesitymorbid obesityVAP-1semicarbazide-sensitive amine oxidaseblood pressureweight reduction
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肥胖在台灣是一個盛行的疾病,導致罹患代謝症候群的比例以及死亡率的增加,但是肥胖的成因、或是肥胖如何導致代謝症候群的原因目前並不清楚。在利用3T3-L1 cell line與誘導後的脂肪細胞所做的differential display研究當中,我們發現了血管附著蛋白-1(vascular adhesion protein-1,簡稱VAP-1)在脂肪細胞分化後表現增加了好幾倍。此外,我們也利用semi-quantitative PCR證實了在肥胖小鼠的脂肪組織中,VAP-1的表現會增加。於是我們進一步探討VAP-1在人類肥胖所扮演的角色。
首先,我們針對20位胖瘦不同的人,利用real-time reverse transcriptional PCR的方法,分析他們腹部脂肪組織VAP-1 mRNA的表現與臨床表徵的關係:發現無論是大網膜或是皮下的脂肪組織,VAP-1 mRNA的表現和身體質量指數(body mass index,BMI)、空腹血糖、空腹胰島素或是血脂肪都沒有顯著相關。
此外,由於之前多位學者的研究報告指出,血中的VAP-1和代謝症候群有相關(雖然結論並不完全一致),所以我們進一步探討病態肥胖的病人在接受胃間隔手術後,血中VAP-1的改變與代謝症候群表徵的改變的關係。此研究共有20位病態肥胖的病人,平均BMI為38.84 kg/m2,我們紀錄下他們的開刀前後的臨床表徵以供分析,結果發現:開刀前,血清中VAP-1的值與空腹血糖成正相關(γ= 0.56,p =0.01),與空腹胰島素值成負相關(γ= -0.51,p = 0.021)。開刀後,血清中VAP-1的變化與腰圍(γ= -0.57,p = 0.011)、舒張壓(γ= -0.56,p = 0.015)及平均動脈壓(γ= -0.46,p = 0.055)的變化有顯著的負相關。在多元線性迴歸模式中,血清中VAP-1的變化在調整過年齡以及性別的影響後,仍可見到與腰圍(β= -2.36,p = 0.014)及舒張壓(β= -3.02,p = 0.017)的變化有顯著的負相關。同時,在調整過年齡以及性別的影響後,舒張壓的變化除了與HOMA-IR的變化有正相關外,也與VAP-1的變化有顯著的負相關。這結果意味著開刀後,血清中VAP-1的變化與腹部肥胖以及舒張壓的變化有關,值得進一步探討在腹部肥胖的病人當中,血清中的VAP-1是否可以調節血壓。
Objective: Circulating vascular adhesion protein-1 (VAP-1) has been shown, although inconsistently, to be associated with various phenotypes defined by metabolic syndrome. The current study explored whether the changes of serum VAP-1 level correlate with the changes in metabolic phenotypes following weight reduction surgery.
Research Methods and Procedures: Clinical characteristics and serum VAP-1 levels in 20 morbidly obese subjects (mean BMI 38.84 kg/m2) were measured before and after gastric partition surgery.
Results: Before surgery, serum VAP-1 levels correlated positively with fasting plasma glucose (γ= 0.56, p =0.01) and negatively with insulin levels (γ= -0.51, p = 0.021). Following surgery, the changes of serum VAP-1 level were negatively correlated with the changes of waist circumferences (γ= -0.57, p = 0.011), diastolic blood pressure (γ= -0.56, p = 0.015), and mean arterial pressure (γ= -0.46, p = 0.055). In multivariate regression, serum VAP-1 levels were negatively correlated with waist circumference (β= -2.36, p = 0.014) and diastolic blood pressure (β= -3.02, p = 0.017) after adjusting for age and gender. The change in diastolic blood pressure was correlated negatively with change of VAP-1 while positively with the change of HOMA-IR.
Discussion: The results suggested that VAP-1 levels were correlated with fasting glucose and insulin levels in morbidly obese subjects. After gastric partition, the changes of VAP-1 level were associated with changes in visceral adiposity and diastolic blood pressure. Serum VAP-1 might modulate diastolic blood pressure independent on the changes of insulin resistance.
口試委員, 指導教授與所長簽名表 1
感想與致謝 2
一、中文摘要(Abstract in Chinese) 4
二、緒論(Introduction) 5
1. 研究背景 5
2. 血管附著蛋白-1(VAP-1)的介紹 6
3. 研究目的及假說 9
三、研究方法及材料(Material and Methods) 10
四、結果(Results) 14
五、討論(Discussion) 17
六、展望: 本結果的臨床應用及貢獻(Perspective) 20
七、英文論文(English manuscript) 22
八、參考文獻(References) 35
九、圖表(Tables & Figures) 42
十、倫理委員會審查書 59
Abella, A., Marti, L., Camps, M., Claret, M., Fernandez-Alvarez, J., Gomis, R., Guma, A., Viguerie, N., Carpene, C., Palacin, M., Testar, X., and Zorzano, A. Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki Rats. Diabetes 2003; 52(4):1004-1013.
Ahmad, F., Azevedo, J. L. J., Cortright, R., Dohm, G. L., and Goldstein, B. J. Alterations in skeletal muscle protein-tyrosine phosphatase activity and expression in insulin-resistant human obesity and diabetes. J Clin Invest 1997; 100:449-458.
Allison, D. B., Fontaine, K. R., Manson, J. E., Stevens, J., and VanItallie, T. B. Annual deaths attributable to obesity in the United States. JAMA 1999; 284:1530-1538.
Arvilommi, A. M., Salmi, M., and Jalkanen, S. Organ-selective regulation of vascular adhesion protein-1 expression in man. Eur.J Immunol. 1997; 27(7):1794-1800.
Bonithon-Kopp, C., Raison, J., Courbon, D., Bonhomme, G., Guy-Grand, B., and Ducimetiere, P. Relationships between 3-y longitudinal changes in body mass index, waist-to-hip ratio, and metabolic variables in an active French female population. Am J Clin Nutr 1992; 56(3):475-482.
Bono, P., Salmi, M., Smith, D. J., and Jalkanen, S. Cloning and characterization of mouse vascular adhesion protein-1 reveals a novel molecule with enzymatic activity. J Immunol. 6-1-1998; 160(11):5563-5571.
Boomsma, F., Bhaggoe, U. M., van der Houwen, A. M., and van den Meiracker, A. H. Plasma semicarbazide-sensitive amine oxidase in human (patho)physiology. Biochim.Biophys.Acta 4-11-2003; 1647(1-2):48-54.
Boomsma, F., de Kam, P. J., Tjeerdsma, G., van den Meiracker, A. H., and van Veldhuisen, D. J. Plasma semicarbazide-sensitive amine oxidase (SSAO) is an independent prognostic marker for mortality in chronic heart failure. Eur.Heart J 2000; 21(22):1859-1863.
Boomsma, F., van den Meiracker, A. H., Winkle, S., Aanstoot, H. J., Batstra, M. R., Man in ''t Veld, A. J., and Bruining, J. Circulating semicarbazide-sensitive amine oxidase is raised both in Type I (insulin-dependent), in Type II (non-insulin-dependent) diabetes mellitus and even in childhood Type I diabetes at first clinical diagnosis. Diabetologia 1999; 42:233-237.
Borecki, I. B., Blangero, J., Rice, T., Perusse, L., Bouchard, C., and Rao, D. C. Evidence for at least two major loci influencing human fatness. Am J Hum.Genet 1998; 63(3):831-838.
Bouchard, C., Rice, T., Lemieux, S., Despres, J. P., Perusse, L., and Rao, D. C. Major gene for abdominal visceral fat area in the Quebec Family Study. Int J Obes Relat Metab Disord 1996; 20(5):420-427.
Calle, E. E., Thun, M. J., Petrelli, J. M., Rodruguez, C., and Heath Jr, C. W. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999; 341:1097-1105.
Carmelli, D., Cardon, L. R., and Fabsitz, R. Clustering of hypertension, diabetes, and obesity in adult male twins: same genes or same environments?? Am J Hum.Genet 1994; 55(3):566-573.
Chan, D. C., Watts, G. F., Barrett, P. H., and Burke, V. Waist circumference, waist-to-hip ratio and body mass index as predictors of adipose tissue compartments in men. QJM. 2003; 96(6):441-447.
Chan, J. M., Rimm, E. B., Coklitz, G. A., Stampfer, M. J., and Willett, W. C. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes care 1994; 17:961-969.
Chen KM, Lee WJ, Lai HS, and Chen WJ. Fifteen years'' experience with gastric partitioning for obesity treatment. J Formos Med Assoc 1998; 97:381-386.
Chen, H., Charlat, O., Tartaglia, L. A., Woolf, E. A., Weng, X., Ellis, S. J., Lakey, N. D., Culpepper, J., Moore, K. J., Breitbart, R. E., Duyk, G. M., Tepper, R. I., and Morgenstern, J. P. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 2-9-1996; 84(3):491-495.
Coleman, D. L. and Hummel, K. P. Hyperinsulinemia in pre-weaning diabetes (db) mice. Diabetologia 1974; 10 Suppl:607-610.
Colilla, S., Rotimi, C., Cooper, R., Goldberg, J., and Cox, N. Genetic inheritance of body mass index in African-American and African families. Genet Epidemiol. 2000; 18(4):360-376.
Comuzzie, A. G., Blangero, J., Mahaney, M. C., Mitchell, B. D., Hixson, J. E., Samollow, P. B., Stern, M. P., and MacCluer, J. W. Major gene with sex-specific effects influences fat mass in Mexican Americans. Genet Epidemiol. 1995; 12(5):475-488.
Consensus Development Conference Statement. Gastrointestinal surgery for severe obesity. Ann Intern Med 1991; 115:956.
Dowling, H. J. and Pi-Sunyer, F. X. Race-dependent health risks of upper body obesity. Diabetes 1993; 42:537-543.
Fabsitz, R. R., Carmelli, D., and Hewitt, J. K. Evidence for independent genetic influences on obesity in middle age. Int J Obes Relat Metab Disord 1992; 16(9):657-666.
Feitosa, M. F., Borecki, I., Hunt, S. C., Arnett, D. K., Rao, D. C., and Province, M. Inheritance of the waist-to-hip ratio in the National Heart, Lung, and Blood Institute Family Heart Study. Obes Res 2000a; 8(4):294-301.
Feitosa, M. F., Rice, T., Nirmala, A., and Rao, D. C. Major gene effect on body mass index: the role of energy intake and energy expenditure. Hum.Biol 2000b; 72(5):781-799.
Garpenstrand, H., Ekblom, J., Backlund, L. B., Oreland, L., and Rosenqvist, U. Elevated plasma semicarbazide-sensitive amine oxidase (SSAO) activity in type 2 diabetes mellitus complicated by retinopathy. Diabet Med 1999; 16:514-521.
Gokturk, C., Nilsson, J., Nordquist, J., Kristensson, M., Svensson, K., Soderberg, C., Israelson, M., Garpenstrand, H., Sjoquist, M., Oreland, L., and Forsberg-Nilsson, K. Overexpression of semicarbazide-sensitive amine oxidase in smooth muscle cells leads to an abnormal structure of the aortic elastic laminas. Am.J.Pathol. 2003; 163(5):1921-1928.
Jaakkola, K., Kaunismaki, K., Tohka, S., Yegutkin, G., Vanttinen, E., Havia, T., Pelliniemi, L. J., Virolainen, M., Jalkanen, S., and Salmi, M. Human vascular adhesion protein-1 in smooth muscle cells. Am.J Pathol. 1999; 155(6):1953-1965.
Jee, S. H., Kim, M. T., Lee, S. Y., and Beaty, T. H. Segregation analysis of waist circumference, hip circumference and waist-to-hip ratio in the Korean Nationwide Family Study. Int J Obes Relat Metab Disord 2002; 26(2):228-233.
Koutroubakis, I. E., Petinaki, E., Vardas, E., Dimoulios, P., Roussomoustakaki, M., Maniatis, A. N., and Kouroumalis, E. A. Circulating soluble vascular adhesion protein 1 in patients with inflammatory bowel disease. Eur.J Gastroenterol.Hepatol. 2002; 14(4):405-408.
Kuczmarski, R. J., Carrol, M. D., Flegal, K. M., and Troiano, R. P. Varying body mass index cutoff points to describe overweight prevalence among U.S. adults: NHANES III (1988 to 1994). Obes Res 1997; 5:542-548.
Kurkijarvi, R., Adams, D. H., Leino, R., Mottonen, T., Jalkanen, S., and Salmi, M. Circulating form of human vascular adhesion protein-1 (VAP-1): increased serum levels in inflammatory liver diseases. J Immunol. 8-1-1998; 161(3):1549-1557.
Kurkijarvi, R., Yegutkin, G. G., Gunson, B. K., Jalkanen, S., Salmi, M., and Adams, D. H. Circulating soluble vascular adhesion protein 1 accounts for the increased serum monoamine oxidase activity in chronic liver disease. Gastroenterology 2000; 119(4):1096-1103.
Langford, S. D., Trent, M. B., Balakumaran, A., and Boor, P. J. Developmental vasculotoxicity associated with inhibition of semicarbazide-sensitive amine oxidase. Toxicol Appl Pharmacol 1999; 155:-237.
Lapidus, L., Bengtsson, C., Larsson, B., Pennert, K., Elisabeth, R., and Sjostrom, L. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow up of participants in the population study of women in Gothenburg, Sweden. Br Med J 1984; 289:1257-1261.
Larsson, B., Svardsudd, K., Welin, L., Wilhelmsen, L., Bjorntorp, P., and Tibblin, G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. Br Med J 1984; 288:1401-1404.
Lavine, R. L., Chick, W. L., Like, A. A., and Makdisi, T. W. Glucose tolerance and insulin secretion in neonatal and adult mice. Diabetes 1971; 20(3):134-139.
Lecomte, E., Herbeth, B., Nicaud, V., Rakotovao, R., Artur, Y., and Tiret, L. Segregation analysis of fat mass and fat-free mass with age- and sex-dependent effects: the Stanislas Family Study. Genet Epidemiol. 1997; 14(1):51-62.
Lee, G. H., Proenca, R., Montez, J. M., Carroll, K. M., Darvishzadeh, J. G., Lee, J. I., and Friedman, J. M. Abnormal splicing of the leptin receptor in diabetic mice. Nature 2-15-1996; 379(6566):632-635.
Lee,WJ, I R Lai, M T Huang, C C Wu, P L Wei. laparoscopic versus open vertical banded gastroplasty for the treatment of morbid obesity. Surg Laparosc Endosc Percutan Tech 11[1], 9-13. 2001.
Ref Type: Journal (Full)
Like, A. A. and Chick, W. L. Studies in the diabetic mutant mouse. I. Light microscopy and radioautography of pancreatic islets. Diabetologia 1970a; 6(3):207-215.
Like, A. A. and Chick, W. L. Studies in the diabetic mutant mouse. II. Electron microscopy of pancreatic islets. Diabetologia 1970b; 6(3):216-242.
Lin, W. H., Tai, T. Y., Wang, P. H., and Chuang, L. M. Identification of differentially expressed genes during adipocyte differentiation and the effect of rosiglitazone on adipocyte gene expression. J Genet Mol Genet 2002; 13:28-43.
Lin, Y. C., Yen, L. L., Chen, S. Y., Kao, M. D., Tzeng, M. S., Huang, P. C., and Pan, W. H. Prevalence of overweight and obesity and its associated factors: findings from National Nutrition and Health Survey in Taiwan, 1993?996. Prev Med 2003; 37(3):233-241.
Lyon, C. J., Law, R. E., and Hsueh, W. A. Minireview: adiposity, inflammation, and atherogenesis. Endocrinology 2003b; 144(6):2195-2200.
Lyon, C. J., Law, R. E., and Hsueh, W. A. Minireview: adiposity, inflammation, and atherogenesis. Endocrinology 2003a; 144(6):2195-2200.
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., and Turner, R. C. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28(7):412-419.
Mercier, N, Moldes, M, El, Hadri K, and Feve, B. Semicarbazide-sensitive amine oxidase activation promotes adipose conversion of 3T3-L1 cells. Biochem J 2001; 358:335-342.
Meszaros, Z, Szombathy, T, Raimondi, L, Karadi, I, Romics, L, and Magyar, K. Elevated serum semicarbazide-sensitive amine oxidase activity in non-insulin-dependent diabetes mellitus: correlation with body mass index and serum triglyceride. Metabolism 1999; 48(1):113-117.
Must, A., Spadano, J., Coakley, E. H., Field, A. E., Colditz, G., and Dietz, W. H. The disease burden associated with overweight and obesity. JAMA 1999; 282:1523-1529.
Nath, S. K., Chakravarti, A., Chen, C. H., Cooper, R., Weder, A., and Schork, N. J. Segregation analysis of blood pressure and body mass index in a rural US community. Hum.Biol 2002; 74(1):11-23.
National institutes of health, 1998, Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults.
Nilsson, S. E., Trydin, N, and Tufvesson, G. Serum monoamine oxidase in diabetes mellitus and some other internal diseases. Acta Med Scand 1968; 184:105-108.
Pei, D, Jones, C. N. O., Bhargava, R., Chen, Y.-D. I., and Reaven, G. M. Evaluation of octreotide to assess insulin-mediated glucose disposal by the insulin suppression test. Diabetologia 1994; 37:843-845.
Price, R. A. and Gottesman, I. I. Body fat in identical twins reared apart: roles for genes and environment. Behav.Genet 1991; 21(1):1-7.
Rice, T., Borecki, I. B., Bouchard, C., and Rao, D. C. Segregation analysis of fat mass and other body composition measures derived from underwater weighing. Am J Hum.Genet 1993; 52(5):967-973.
Rice, T., Sjostrom, C. D., Perusse, L., Rao, D. C., Sjostrom, L., and Bouchard, C. Segregation analysis of body mass index in a large sample selected for obesity: the Swedish Obese Subjects study. Obes Res 1999; 7(3):246-255.
Salmi, M. and Jalkanen, S. A 90-kilodalton endothelial cell molecule mediating lymphocyte binding in humans. Science 1992; 257:1407-1409.
Salmi, M. and Jalkanen, S. VAP-1: an adhesin and an enzyme. Trends Immunol. 2001; 22(4):211-216.
Salmi, M., Stolen, C., Jousilahti, P., Yegutkin, G. G., Tapanainen, P., Janatuinen, T., Knip, M., Jalkanen, S., and Salomaa, V. Insulin-regulated increase of soluble vascular adhesion protein-1 in diabetes. Am.J Pathol. 2002; 161(6):2255-2262.
Salmi, M., Tohka, S., Berg, E. L., Butcher, E. C., and Jalkanen, S. Vascular adhesion protein 1 (VAP-1) mediates lymphocyte subtype-specific, selectin-independent recognition of vascular endothelium in human lymph nodes. J Exp.Med 8-18-1997; 186(4):589-600.
Saltiel, A. R. and Kahn, C. R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001; 414:799-806.
Smith, D. J., Salmi, M., Bono, P., Hellman, J., Leu, T., and Jalkanen, S. Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion molecule. J Exp.Med 7-6-1998; 188(1):17-27.
Sorensen, T. I., Holst, C., Stunkard, A. J., and Skovgaard, L. T. Correlations of body mass index of adult adoptees and their biological and adoptive relatives. Int J Obes Relat Metab Disord 1992; 16(3):227-236.
Sowers, J. R. Obesity as a cardiovascular risk factor. Am J Med 2003; 115(8A):37S-41S.
Stewart, K. J., DeRegis, J. R., Turner, K. L., Bacher, A. C., Sung, J., Hees, P. S., Shapiro, E. P., Tayback, M., and Ouyang, P. Usefulness of anthropometrics and dual-energy X-ray absorptiometry for estimating abdominal obesity measured by magnetic resonance imaging in older men and women. J Cardiopul Rehabil 2003; 23:109-114.
Stunkard, A. J., Foch, T. T., and Hrubec, Z. A twin study of human obesity. JAMA 7-4-1986; 256?(1):51-54.
Stunkard, A. J., Harris, J. R., Pedersen, N. L., and McClearn, G. E. The body-mass index of twins who have been reared apart. N Engl J Med 5-24-1990; 322(21):1483-1487.
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