Thromb Haemost 1999; 82(05): 1490-1496
DOI: 10.1055/s-0037-1614860
Rapid Communications
Schattauer GmbH

Relationship between Visceral Fat and PAI-1 in Overweight Men and Women before and after Weight Loss

M. Kockx
1   From the Gaubius Laboratory TNO-PG, Leiden, The Netherlands
,
R. Leenen*
2   Department of Chronic Diseases and Environmental Epidemiology, National Institute of Public Health and The Environment, Bilthoven, The Netherlands
,
J. Seidell
2   Department of Chronic Diseases and Environmental Epidemiology, National Institute of Public Health and The Environment, Bilthoven, The Netherlands
,
H. M. G. Princen
1   From the Gaubius Laboratory TNO-PG, Leiden, The Netherlands
,
T. Kooistra
1   From the Gaubius Laboratory TNO-PG, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 03 November 1998

Accepted after resubmission 27 May 1999

Publication Date:
09 December 2017 (online)

Summary

This study was aimed at evaluating the relationship between visceral fat accumulation and plasma plasminogen activator inhibitor-1 (PAI-1) levels in healthy, obese men and women undergoing weight loss therapy. The subjects, 25 men and 25 premenopausal women, aged between 26 and 49 years, with an initial body mass index between 28 and 38 kg/m2, received a controlled diet for 13 weeks providing a 4.2 MJ/day energy deficit. Magnetic resonance imaging was used to measure visceral and subcutaneous abdominal fat. Our results show that before weight loss visceral fat was significantly correlated with PAI-1 in men (r = 0.45; p <0.05), but not in women (r = -0.15; ns). The association between visceral fat and PAI-1 in men remained significant after adjustment for age and total fat mass, and multiple linear regression analysis showed a significant independent contribution of visceral fat to plasma PAI-1 levels. Both visceral fat areas and PAI-1 levels decreased significantly with weight loss in both men and women. Changes in visceral fat area were related to changes in PAI-1 in women (r = -0.43; p = 0.05) but not in men (r = -0.01; ns); however, this association in women disappeared after adjustment for total fat mass. We conclude that there is a relationship between visceral fat and PAI-1 in obese men but not in obese women, and that PAI-1 levels decrease substantially (52%) by weight loss, but this change is not related to changes in visceral fat mass per se.

* Present address: Dr. R. Leenen, Unilever Research Laboratory, Vlaardingen, The Netherlands


 
  • References

  • 1 Rosenbaum M, Leibel RL, Hirsch J. Obesity. N Engl J Med 1997; 337: 396-407.
  • 2 Vague P, Juhan-Vague I, Chabert V, Alessi MC, Atlan C. Fat distribution and plasminogen activator inhibitor activity in nondiabetic obese women. Metabolism 1989; 38: 913-5.
  • 3 Vague P, Juhan-Vague I, Aillaud MF, Badier C, Viard R, Alessi MC, Collen D. Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects. Metabolism 1986; 35: 250-3.
  • 4 McGill JB, Schneider DJ, Arfken CL, Lucore CL, Sobel BE. Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients. Diabetes 1994; 43: 104-9.
  • 5 Hamsten A, Wiman B, De Faire U, Blomback M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-63.
  • 6 Wiman B, Hamsten A. The fibrinolytic enzyme system and its role in the etiology of thromboembolic disease. Semin Thromb Haemost 1990; 16: 207-16.
  • 7 Auwerx J, Bouillon R, Collen D, Geboers J. Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis 1988; 8: 68-72.
  • 8 Carmeliet P, Collen D. Molecular genetics of the fibrinolytic and coagulation systems in haemostasis, thrombogenesis, restenosis and atherosclerosis. Curr Opin Lipidol 1997; 8: 118-25.
  • 9 Larsson B, Svardsudd K, Welin L, Bjorntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow of participants in the study of men born in 1913. Br Med J 1984; 228: 1401-4.
  • 10 Lapidus L, Bengtsson C, Larsson B, Pennert K, Rybo E, 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: 1257-61.
  • 11 Shimomura I, Funahashi T, Takahashi K, Maeda K, Kotani K, Nakamura T, Yamashita S, Miura M, Fukuda Y, Takemura K, Tokunaga K, Matsuzawa Y. Enhanced expression of PAI-1 in visceral fat: Possible contribution to vascular disease in obesity. Nature Medicine 1996; 2: 800-3.
  • 12 Janand-Delenne B, Chagnaud C, Raccah D, Alessi MC, Juhan-Vague I, Vague P. Visceral fat as a main determinant of plasminogen activator inhibitor 1 level in women. Int J Obesity 1998; 22: 312-7.
  • 13 Cigolini M, Targher G, Bergamo Andreis IA, Tonoli M, Agostino G, De Sandre G. Visceral fat accumulation and its relation to plasma hemostatic factors in healthy men. Arterioscler Thromb Vasc Biol 1996; 16: 368-74.
  • 14 Ferguson MA, Gutin B, Owens S, Litaker M, Tracy RP, Allison J. Fat distribution and hemostatic measures in obese children. Am J Clin Nutr 1998; 67: 1136-40.
  • 15 Loskutoff DJ, Samad F. The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arterioscler Thromb Vasc Biol 1998; 18: 1-6.
  • 16 Samad F, Loskutoff DJ. Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice. Molecul Med 1996; 2: 568-82.
  • 17 Alessi MC, Peiretti F, Morange P, Henry M, Nalbone F, Juhan-Vague I. Production of plasminogen activator inhibitor 1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease. Diabetes 1997; 46: 860-7.
  • 18 Kissebah AH, Krakower GR. Regional adiposity and morbidity. Physiol Rev 1994; 74: 761-811.
  • 19 Juhan-Vague I, Alessi MC. PAI-1, obesity, insulin resistance and risk of cardiovascular events. Thromb Haemost 1997; 78: 656-60.
  • 20 Carey DGP. Abdominal obesity. Curr Opin Lipidol 1998; 9: 35-40.
  • 21 Van Kesteren PJM, Kooistra T, Lansink M, Van Kamp GJ, Asscheman H, Gooren LJG, Emeis JJ, Vischer UM, Stehouwer CDA. The effects of sex steroids on plasma levels of marker proteins of endothelial cell functioning. Thromb Haemost 1998; 79: 1029-33.
  • 22 Kirschner MA, Samojlik E. Sex hormone metabolism in upper and lower body obesity. Int J Obes 1991; 15: 101-8.
  • 23 Primrose JN, Davies JA, Prentice CR, Hughes R, Johnston D. Reduction in factor VII, fibrinogen and plasminogen activator inhibitor-1 activity after surgical treatment of morbid obesity. Thromb Haemost 1992; 68: 396-9.
  • 24 Marckmann P, Toubro S, Astrup A. Sustained improvement in blood lipids, coagulation, and fibrinolysis after major weight loss in obese subjects. Eur J Clin Nutr 1998; 52: 329-33.
  • 25 Folsom AR, Qamhieh HT, Wing RR, Jeffery RW, Stinson VL, Kuller LH, Wu KK. Impact of weight loss on plasminogen activator inhibitor (PAI-1), factor VII, and other hemostatic factors in moderately overweight adults. Arterioscler Thromb 1993; 13: 162-9.
  • 26 Van der Kooy K, Leenen R, Deurenberg P, Seidell JC, Westerterp KR, Hautvast JG. Changes in fat-free mass in obese subjects after weight loss: a comparison of body composition measures. Int J Obes Relat Metab Disord 1992; 16: 675-83.
  • 27 Leenen R, Van der Kooy K, Seidell JC, Deurenberg P. Visceral fat accumulation measured by magnetic resonance imaging in relation to serum lipids in obese men and women. Atherosclerosis 1992; 94: 171-81.
  • 28 Weststrate JA, Hautvast JG. The effects of short-term carbohydrate overfeeding and prior exercise on resting metabolic rate and diet-induced thermogenesis. Metabolism 1990; 39: 1231-9.
  • 29 Kluft C, Meijer P. Update 1996: Blood collection and handling procedures for assessment of plasminogen activators and inhibitors (Leiden fibrinolysis workshop). Fibrinolysis 1996; 171-9.
  • 30 Siedel J, Hagele EO, Ziegenhorn J, Wahlefeld AW. Reagent for the enzymatic determination of serum total cholesterol with improved lipolytic efficiency. Clin Chem 1983; 29: 1075-80.
  • 31 Warnick GR, Benderson J, Albers JJ. Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. Clin Chem 1982; 28: 1379-88.
  • 32 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502.
  • 33 Landeghem AA, Poortman J, Deshpande N, Di Martino L, Tarquini A, Thijssen JH, Schwartz F. Plasma concentration gradient of steroid hormones across human mammary tumours in vivo. J Steroid Biochem 1981; 14: 741-7.
  • 34 Nanjee MN, Wheeler MJ. Plasma free testosterone-is an index sufficient?. Ann Clin Biochem 1985; 22: 387-90.
  • 35 Moore JW, Clark GM, Bulbrook RD, Hayward JL, Murai JT, Hammond GL, Siiteri PK. Serum concentrations of total and non-protein-bound oestradiol in patients with breast cancer and in normal controls. Int J Cancer 1982; 29: 17-21.
  • 36 Siri WE. The gross composition of the body. In: Advances in biological and medical physics IV. Tobias CA, Lawrence JH. eds New York: The Academic Press; 1956: 239-80.
  • 37 Seidell JC, Bakker CJ, Van der Kooy K. Imaging techniques for measuring adipose-tissue distribution-a comparison between computed tomography and 1.5-T magnetic resonance. Am J Clin Nutr 1990; 51: 953-7.
  • 38 Giltay EJ, Elbers JMH, Gooren LJG, Emeis JJ, Kooistra T, Asscheman H, Stehouwer CDA. Visceral fat accumulation is an important determinant of PAI-1 levels in young, nonobese men and women. Arterioscler Thromb Vasc Biol 1998; 18: 1716-22.
  • 39 Targher G, Tonoli M, Agostino G, Rigo L, Boschini K, Muggeo M, De Sandre G, Cigolini M. Ultrasonographic intra-abdominal depth and its relation to haemostatic factors in healthy males. Int J Obes 1996; 20: 882-5.
  • 40 Seidell JC, Bouchard C. Visceral fat in relation to health: is it a major culprit or simply an innocent bystander?. Int J Obes 1997; 21: 626-31.
  • 41 Eriksson P, Reynisdottir S, Lonnqvist F, Stemme V, Hamsten A, Arner P. Adipose tissue secretion of plasminogen activator inhibitor-1 in non-obese and obese individuals. Diabetologia 1998; 41: 65-71.
  • 42 Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumour necrosis factor- in human obesity and insulin resistance. J Clin Invest 1995; 95: 2409-15.
  • 43 Samad F, Yamamoto T, Loskutoff DJ. Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo. J Clin Invest 1996; 97: 37-46.
  • 44 Samad F, Yamamoto T, Pandey M, Loskutoff DJ. Elevated expression of transforming growth factor- in adipose tissue from obese mice. Mol Med 1997; 3: 37-48.
  • 45 Morange P, Alessi MC, Ventura N, Verdier M, Casanova D, Magalon G, Juhan-Vague I. PAI-1 antigen production by human adipose tissue is correlated with that of TNF. Fibrinolysis 1998; 12: 33
  • 46 Potter van Loon BJ, Kluft C, Radder JK, Blankenstein MA, Meinders AE. The cardiovascular risk factor plasminogen activator inhibitor type 1 is related to insulin resistance. Metabolism 1993; 42: 945-9.
  • 47 Henry M, Tregoët KA, Alessi MC, Aillaud MF, Visvikis S, Siest G, Tiret L, Juhan-Vague I. Metabolic determinants are much more important than genetic polymorphisms in determining the PAI-1 activity and antigen plasma concentrations. A family study with part of the Stanislas Cohort. Arterioscler Thromb Vasc Biol 1998; 18: 84-91.
  • 48 Juhan-Vague I, Alessi MC, Vague P. Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin-dependent diabetes mellitus. Ann Med 1996; 28: 371-80.
  • 49 Gebara OC, Mittleman MA, Sutherland P, Lipinska DI, Matheney T, Xu P, Welty FK, Wilson PW, Levy D, Muller JE. Association between increased estrogen status and increased fibrinolytic potential in the Framingham Offspring Study. Circulation 1995; 91: 1952-8.
  • 50 Shahar E, Folsom AR, Salomaa VV, Stinson VL, McGovern PG, Shimakawa T, Chambless LE, Wu KK. Relation of hormone-replacement therapy to measures of plasma fibrinolytic activity. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation 1996; 93: 1970-5.
  • 51 Chandler WL, Alessi MC, Aillaud MF, Henderson P, Vague P, Juhan-Vague I. Clearance of tissue plasminogen activator (TPA) and TPA/plasminogen activator inhibitor type 1 (PAI-1) complex: relationship to elevated TPA antigen in patients with high PAI-1 activity levels. Circulation 1997; 96: 761-8.