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Horm Metab Res 2003; 35(3): 178-182
DOI: 10.1055/s-2003-39078
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Differences in Plasminogen Activator Inhibitor 1 in Subcutaneous Versus Omental Adipose Tissue in Non-Obese and Obese Subjects

G.  He1 , S.  B.  Pedersen1 , J.  M.  Bruun1 , A.  S.  Lihn1 , P.  F.  Jensen1 , B.  Richelsen1
  • 1Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, and Department of Surgical Gastroenterology L, Aarhus Kommehospital, Aarhus University Hospital, Aarhus C., Denmark
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Publication History

Received 21 October 2002

Accepted after revision 5 December 2002

Publication Date:
07 May 2003 (online)

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Abstract

Human adipose tissue can produce plasminogen activator inhibitor-1 (PAI-1). It has been suggested that high levels of PAI-1 are of importance in enhanced cardiovascular disease observed among obese subjects, especially abdominally obese individuals. In the present study, we investigated the level of mRNA and production of PAI-1 in adipose tissue from two adipose tissue depots (omental vs. subcutaneous). Adipose tissue from both depots was obtained from obese (mean BMI, 46.9 kg/m2) and non-obese (mean BMI, 23.9 kg/m2) women. PAI-1 mRNA was measured both in fresh adipose tissue obtained immediately after surgery and after the adipose tissue (fragments) had been incubated for up to 72 h. In immediately frozen adipose tissue, PAI-1 mRNA expression was similar in omental and subcutaneous adipose tissue. No differences between obese and non-obese women were found. However, when adipose tissue fragments were cultured, PAI-1 mRNA and PAI-1 production were significantly higher in omental than in subcutaneous adipose tissue (p < 0.05). In the culture system, the production of PAI-1 in obese subjects was higher than in non-obese subjects in both subcutaneous (p < 0.05) and in omental adipose tissue (p = 0.19). In order to test whether these regional differences observed after incubation of the adipose tissue were due to differences in local accumulation of cytokines that may stimulate PAI-1 by a paracrine or autocrine manner, we investigated the expression of transforming growth factor β1 (TGF-β1) mRNA and tumor necrosis factor α (TNF-α) mRNA and protein. No differences between the two fat depots were found. In conclusion, no differences in PAI-1 expression between omental and subcutaneous adipose tissue were observed in biopsies frozen immediately after removal, but after incubation of adipose tissue (which somehow stimulates PAI-1 production), higher levels of PAI-1 were found in omental adipose tissue than in subcutaneous adipose tissue. Finally, PAI-1 production in adipose tissue from obese women was higher in non-obese women after incubation for 72 h.

Key words

Plasminogen Activator Inhibitor-1 - Human Adipose Tissue - Subcutaneous - Omental - Gene Expression - Obesity

References

  • 1 Bastard J P, Pieroni L, Hainque B. Relationship between plasma plasminogen activator inhibitor 1 and insulin resistance.  Diabetes Metab Res Rev. 2000;  16 192-201
    CrossrefPubMedGoogle Scholar
  • 2 Juhan-Vague I, Alessi M C. PAI-1, obesity, insulin resistance and risk of cardiovascular events.  Thromb Haemost. 1997;  78 656-660
    PubMedGoogle Scholar
  • 3 Poirier P, Eckel R H. Obesity and cardiovascular disease.  Curr Atheroscler Rep. 2002;  4 448-453
    PubMedGoogle Scholar
  • 4 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
    CrossrefPubMedGoogle Scholar
  • 5 Alessi M C, Peiretti F, Morange P, 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;  46 860-867
    CrossrefPubMedGoogle Scholar
  • 6 Juhan-Vague I, Vague P, Alessi M C, Badier C, Valadier J, Aillaud M F, Atlan C. Relationships between plasma insulin triglyceride, body mass index, and plasminogen activator inhibitor 1.  Diabete Metab. 1987;  13 331-336
    PubMedGoogle Scholar
  • 7 Vague P, Juhan-Vague I, Aillaud M F, Badier C, Viard R, Alessi M C, 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;  35 250-253
    CrossrefPubMedGoogle Scholar
  • 8 Mertens I, van der Planken M, Corthouts B, Wauters M, Peiffer F, de Leeuw I, van Gaal L. Visceral fat is a determinant of PAI-1 activity in diabetic and non- diabetic overweight and obese women.  Horm Metab Res. 2001;  33 602-607
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Janand-Delenne B, Chagnaud C, Raccah D, Alessi M C, Juhan-Vague I, Vague P. Visceral fat as a main determinant of plasminogen activator inhibitor 1 level in women.  Int J Obes Relat Metab Disord. 1998;  22 312-317
    CrossrefPubMedGoogle Scholar
  • 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.  Nat Med . 1996;  2 800-803
    CrossrefPubMedGoogle Scholar
  • 11 Giltay E J, Elbers J M, Gooren L J, Emeis J J, Kooistra T, Asscheman H, Stehouwer C D. Visceral fat accumulation is an important determinant of PAI-1 levels in young, nonobese men and women: modulation by cross-sex hormone administration.  Arterioscler Thromb Vasc Biol. 1998;  18 1716-1722
    PubMedGoogle Scholar
  • 12 Mavri A, Stegnar M, Krebs M, Sentocnik J T, Geiger M, Binder B R. Impact of adipose tissue on plasma plasminogen activator inhibitor-1 in dieting obese women.  Arterioscler Thromb Vasc Biol. 1999;  19 1582-1587
    CrossrefPubMedGoogle Scholar
  • 13 Arner P. Regional differences in protein production by human adipose tissue.  Biochem Soc Trans . 2001;  29 72-75
    CrossrefPubMedGoogle Scholar
  • 14 Vidal H. Gene expression in visceral and subcutaneous adipose tissues.  Ann Med. 2001;  33 547-555
    CrossrefPubMedGoogle Scholar
  • 15 Montague C T, Prins J B, Sanders L, Digby J E, O'Rahilly S. Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution.  Diabetes. 1997;  46 342-347
    CrossrefPubMedGoogle Scholar
  • 16 Cigolini M, Tonoli M, Borgato L, Frigotto L, Manzato F, Zeminian S, Cardinale C, Camin M, Chiaramonte E, de Sandre G, Lunardi C. Expression of plasminogen activator inhibitor-1 in human adipose tissue: a role for TNF-alpha.  Atherosclerosis. 1999;  143 81-90
    CrossrefPubMedGoogle Scholar
  • 17 Halleux C M, Declerck P J, Tran S L, Detry R, Brichard S M. Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines.  J Clin Endocrinol Metab. 1999;  84 4097-4105
    CrossrefPubMedGoogle Scholar
  • 18 Bastelica D, Morange P, Berthet B, Borghi H, Lacroix O, Grino M, Juhan-Vague I, Alessi M C. Stromal cells are the main plasminogen activator inhibitor-1-producing cells in human fat: evidence of differences between visceral and subcutaneous deposits.  Arterioscler Thromb Vasc Biol . 2002;  22 173-178
    CrossrefPubMedGoogle Scholar
  • 19 Morange P E, Alessi M C, 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 1361-1365
    PubMedGoogle Scholar
  • 20 Eriksson P, van Harmelen V, Hoffstedt J, Lundquist P, Vidal H, Stemme V, Hamsten A, Arner P, Reynisdottir S. Regional variation in plasminogen activator inhibitor-1 expression in adipose tissue from obese individuals.  Thromb Haemost . 2000;  83 545-548
    PubMedGoogle Scholar
  • 21 Polac I, Cierniewska-Cieslak A, Stachowiak G, Pertynski T, Cierniewski C S. Similar PAI-1 expression in visceral and subcutaneous fat of postmenopausal women.  Thromb Res. 2001;  102 397-405
    CrossrefPubMedGoogle Scholar
  • 22 Gottschling-Zeller H, Birgel M, Rohrig K, Hauner H. Effect of tumor necrosis factor alpha and transforming growth factor beta 1 on plasminogen activator inhibitor-1 secretion from subcutaneous and omental human fat cells in suspension culture.  Metabolism. 2000;  49 666-671
    CrossrefPubMedGoogle Scholar
  • 23 He G, Pedersen S B, Bruun J M, Richelsen B. Regulation of plasminogen activator inhibitor-1 in human adipose tissue: interaction between cytokines, cortisol and estrogen.  Horm Metab Res. 2000;  32 515-520
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Kristensen K, Pedersen S B, Richelsen B. Regulation of leptin by steroid hormones in rat adipose tissue.  Biochem Biophys Res Commun. 1999;  259 624-630
    CrossrefPubMedGoogle Scholar
  • 25 Pedersen S B, Kristensen K, Fisker S, Jorgensen J O, Christiansen J S, Richelsen B. Regulation of uncoupling protein-2 and -3 by growth hormone in skeletal muscle and adipose tissue in growth hormone-deficient adults.  J Clin Endocrinol Metab. 1999;  84 4073-4078
    CrossrefPubMedGoogle Scholar
  • 26 Bruun J M, Pedersen S B, Richelsen B. Interleukin-8 production in human adipose tissue. inhibitory effects of anti-diabetic compounds, the thiazolidinedione ciglitazone and the biguanide metformin.  Horm Metab Res. 2000;  32 537-541
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Alessi M C, Bastelica D, Morange P, Berthet B, Leduc I, Verdier M, Geel O, Juhan-Vague I. Plasminogen activator inhibitor 1, transforming growth factor-beta1, and BMI are closely associated in human adipose tissue during morbid obesity.  Diabetes. 2000;  49 1374-1380
    PubMedGoogle Scholar

Dr. B. Richelsen

Department of Endocrinology and Metabolism C · Aarhus Amtssygehus · Aarhus University Hospital

Tage Hansensgade 2 · 8000 Aarhus C · Denmark

Phone: + 45 (89) 49 76 79

Fax: + 45 (89) 49 76 59

Email: br@aas.auh.dk

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