The presence of obesity increases the risk of thrombotic vascular diseases. The role of fat accumulation and its effect on plasminogen activator inhibitor–1 (PAI–1) levels was investigated in humans and animals. Plasma PAI–1 levels were closely correlated with visceral fat area but not with subcutaneous fat area in human subjects. PAI–1 mRNA was detected in both types of fat tissue in obese rats but increased only in visceral fat during the development of obesity. These data suggest that an enhanced expression of the PAI–1 gene in visceral fat may increase plasma levels and may have a role in the development of vascular disease in visceral obesity.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Larsson, B. et al. 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. 288, 1401–1404 (1984).
Kissebah, A.H. et al. Relation of body fat distribution to metabolic complications of obesity. J. clin. Endocrinol. Metab. 54, 254–260 (1982).
Deprés, J.P. et al. Role of deep abdominal fat in the association between regional adipose tissue distribution and glucose tolerance in obese women. Diabetes 38, 304–309 (1989).
Matsuzawa, Y., Tokunaga, K., Fujioka, S. & Tarui, S. Pathophysiology of visceral fat obesity. in Progress in Obesity Research, (ed. Oomura, Y.) 309–312 (John Libbey, London, 1990).
Nakamura, T. et al. Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men. Atherosclerosis 107, 239–246 (1994).
Wiman, B. & Hamsten, A. The fibrinolytic enzyme system and its role in the etiology of thrombo-embolic disease. J. Biol. Chem. 259, 3644–3647 (1984).
Hamsten, A., Wiman, B., Faire, U.D. & Blomback, M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N. Engl. J. Med. 313, 1557–1563 (1985).
Wiman, B. & Hamsten, A. The fibrinolytic enzyme system and its role in the etiology of thrombotic disease. Semin. Thromb. Haemost. 26, 207–216 (1990).
Auwerx, J., Bouillon, R., Collen, D. & Geboers, J. Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis 8, 68–72 (1988).
Vague, P. et al. Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects. Metabolism 35, 250–253 (1986).
Lucore, C.L., Fujii, S., Wun, T.C., Sobel, B.E. & Billadello, J.J. Regulation of the expression of type 1 plasminogen activator inhibitor in Hep G2 cells by epidermal growth factor. J. Biol. Chem. 263, 15845–15848 (1988).
Kooistra, T. et al. Plasminogen activator inhibitor 1: Biosynthesis and mRNA levels are increased by insulin in cultured human hepatocytes. Thromb. Haemost. 62, 723–728 (1989).
Hotamisligil, G.S., Shargili, N.S. & Spiegelman, B.M. Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance. Science 259, 87–91 (1993).
Hotamisiigil, G.S., Arner, P., Caro, J.F., Atkinson, R.L. & Spiegelman, B.M. Increased adipose tissue expression of tumor necrosis factor-a in human obesity and insulin resistance. J. Clin. Invest. 95, 2409–2415 (1995).
Spiegelman, B.M., Choy, L.:., Hotamisligil, G.S., Graves, R.A. & Tontonoz, P. Regulation of adipocyte gene expression in differentiation and syndromes of obesity/diabetes. J. Biol. Chem. 268, 6823–6826 (1993).
Ailhaud, G., Grimaldi, P. & Negrel, R. Cellular and molecular aspects of adipose tissue development. Annu. Rev. Nutr. 12, 207–233 (1992).
Shimomura, I. et al. Marked reduction of acyl-CoA synthetase activity and mRNA in intra-abdominal visceral fat by physical exercise. Am. J. Physiol. 265, E44E50 (1993).
Björntorp, P. “portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis. 10, 493–496 (1990).
Reaven, G.M. Role of insulin resistance in human disease. Diabetes 37, 1595–1607 (1988).
Tokunaga, K., Matsuzawa, Y., Ishikawa, K. & Tarui, S. A novel technique for the determination of fat by computed tomography. Int. J. Obes. 7, 437–445 (1983).
Fujioka, S., Matsuzawa, Y., Tokunaga, K. & Tarui, S. Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism 36, 54–59 (1987).
Tokunaga, K., Fukushima, M., Kemnitz, J.W. & Bray, G.A. Comparison of ven-tromedial and paraventricular lesions in rats that become obese. Am. J. Physiol. 251, R1221–R1227 (1986).
Funahashi, T. et al. Enhanced expression of rat obese (ob) gene in adipose tissues of ventromedial hypothalamus (VMH)-lesioned rats. Biochem. Biophys. Res. Commun. 211, 469–475 (1995).
About this article
Cite this article
Shimomura, I., Funahasm, T., Takahashi, M. et al. Enhanced expression of PAI–1 in visceral fat: Possible contributor to vascular disease in obeisty. Nat Med 2, 800–803 (1996). https://doi.org/10.1038/nm0796-800
High visceral to subcutaneous fat area ratio predicts early postoperative small bowel obstruction after surgery for colorectal cancer
Langenbeck's Archives of Surgery (2022)
Cellular and Molecular Life Sciences (2022)
Lipids in Health and Disease (2021)
Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe−/− mice
Scientific Reports (2021)
Nature Reviews Endocrinology (2021)