Thromb Haemost 2000; 83(04): 545-548
DOI: 10.1055/s-0037-1613860
Commentary
Schattauer GmbH

Regional Variation in Plasminogen Activator Inhibitor-1 Expression in Adipose Tissue from Obese Individuals

Per Eriksson
1   From the Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institute, Stockholm
,
Vanessa Van Harmelen
2   Department of Medicine, Huddinge Hospital, Karolinska Institute, Stockholm
,
Johan Hoffstedt
2   Department of Medicine, Huddinge Hospital, Karolinska Institute, Stockholm
,
Per Lundquist
3   Department of Surgery, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden
,
Hubert Vidal
4   INSERM Unit 449, Facultéde Médecine R. Laennec, Lyon, France
,
Veronika Stemme
5   Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden
,
Anders Hamsten
1   From the Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institute, Stockholm
,
Peter Arner
2   Department of Medicine, Huddinge Hospital, Karolinska Institute, Stockholm
,
Signy Reynisdottir
2   Department of Medicine, Huddinge Hospital, Karolinska Institute, Stockholm
› Institutsangaben
This project was supported by grants from the Swedish Medical Research Council (8691, 9390, 6816 and 01034), the Swedish Heart-Lung Foundation, Swedish Diabetes Association, Novo Nordic Foundation, the European Commission (HIFMECH study, contract BMH4-CT96-0272 and FATLINK study, contract FAIR-CT-984141), the Marianne and Marcus Wallenberg Foundation, the King Gustaf V 80th Birthday Foundation, the Professor Nanna Svartz Foundation and the Swedish Society of Medicine. P. Eriksson and S. Reynisdottir are supported by post-doctoral fellowships from the Swedish Medical Research Council (12247) and Swedish National Network for Cardiovascular Research (NNCR), respectively.
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Publikationsverlauf

Received 21. Oktober 1999

Accepted 01. Dezember 1999

Publikationsdatum:
08. Dezember 2017 (online)

Summary

High plasma plasminogen activator inhibitor-1 (PAI-1) activity is a frequent finding in obesity and adipose tissue has recently been suggested to be a source of circulating PAI-1 in humans. In the present study, differences in adipose tissue gene expression and protein secretion rate of PAI-1 between subcutaneous and visceral adipose tissue was analysed in specimens obtained from 22 obese individuals. The secretion rate of PAI-1 was two-fold higher in subcutaneous adipose tissue than in visceral adipose tissue (292 ± 50 vs 138 ± 24 ng PAI-1/107 cells, P <0.05). In accordance with the secretion data, subcutaneous adipose tissue contained about three-fold higher levels of PAI-1 mRNA than visceral adipose tissue (2.43 ± 0.37 vs 0.81 ± 0.12 attomole PAI-1 mRNA/µg total RNA, P <0.001). PAI-1 secretion from subcutaneous but not from visceral adipose tissue correlated significantly with cell size (r = 0.43, P <0.05). In summary, subcutaneous adipose tissue secreted greater amounts of PAI-1 and had a higher PAI-1 gene expression than visceral adipose tissue from the same obese individuals. Bearing in mind that subcutaneous adipose tissue is the largest fat depot these finding may be important for the coagulation abnormalities associated with obesity.

 
  • References

  • 1 Hamsten A, Eriksson P. Fibrinolysis and atherosclerosis. Baillieres Clinical Haematology 1995; 08: 345-63.
  • 2 Loskutoff DJ, Samad F. The adipose and hemostatic balance in obesity. Studies on PAI-1. Arterioscler Thromb Vasc Biol 1998; 18: 1-6.
  • 3 Samad F, Yamamoto K, Loskutoff DJ. Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo. Induction by tumor necrosis factor-alpha and lipopolysaccharide. J Clin Invest 1996; 97: 37-46.
  • 4 Alessi MC, Peiretti F, Henry M, Nalbone G, 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.
  • 5 Eriksson P, Reynisdottir S, Lönnqvist 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.
  • 6 Hube F, Lietz U, Igel M, Jensen PB, Tornqvist H, Joost HG, Hauner H. Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans. Horm Metab Res 1996; 28: 690-3.
  • 7 Montague CT, Prins JB, Sanders L, Zhang J, Sewter CP, Digby J, Byrne CD, O´Rahilly S. Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 1998; 47: 1384-1391.
  • 8 Van Harmelen V, Reynisdottir S, Eriksson P, Thörne A, Hoffstedt J, Lönnqvist F, Arner P. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 1998; 47: 913-17.
  • 9 Lefebvre A-M, Laville M, Vega N, Riou JP, van Gaal L, Auwerx J, Vidal H. Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes 1998; 47: 98-103.
  • 10 Shimomura I, Funahashi T, Takahashi M, 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 contributor to vascular disease in obesity. Nature Med 1996; 02: 800-3.
  • 11 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 Obes 1998; 22: 312-17.
  • 12 Large V, Reynisdottir S, Eleborg L, van Harmelen V, Strömmer L, Arner P. Lipolysis in human fat cells obtained under local and general anesthesia. Int J Obes Relat Metab Disord 1997; 21: 78-82.
  • 13 Rodbell M. Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 1964; 239: 375-80.
  • 14 Dole VP, Meinertz H. Microdetermination of long-chain fatty acids in plasma and tissue. J Biol Chem 1960; 235: 2595-9.
  • 15 Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 1995; 95: 2409-15.
  • 16 Arner P, Östman J. Mono- and diacylglycerols in human adipose tissue. Biochim Biophys Acta 1974; 369: 209-21.
  • 17 Auboeuf D, Vidal H. The use of reverse transcription-competitive polymerase chain reaction to investigate the in vivo regulation of gene expression in small tissue samples. Anal Biochem 1997; 245: 141-8.
  • 18 Duserre E, Moulin P, Vidal H. Difference in mRNA expression of the proteins secreted by the adipocytes in human subcutaneous and visceral adipose tissues. Biochim Biophys Acta 2000; 1500: 88-96.
  • 19 Morange PE, Alessi MC, Verdier M, Casanova D, Magalon G, Juhan-Vague I. PAI-1 produced ex vivo by human adipose tissue is relevant to PAI-1 blood level. Arterioscler Thromb Vasc Biol 1999; 19: 1361-5.
  • 20 Crandall DL, Quinet EM, Morgan GA, Busler DE, McHendry-Rinde B, Kral JG. Synthesis and secretion of plasminogen activator inhibitor-1 by human preadipocytes. J Clin Endocrinol Metab 1999; 84: 3222-7.