on May 15, 2003
Published online before print May 15, 2003, doi: 10.1161/01.ATV.0000077401.36885.BB
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 7, 2003
Accepted on April 17, 2003
Plasma PAI-1 Levels Are More Strongly Related to Liver Steatosis Than to Adipose Tissue Accumulation
Marie-Christine Alessi *;
From the Laboratory of Hematology (M.-C.A., D.B., A.M., P.M., I.J.-V.), EPI 99[hyphen]36, Faculty of Medicine, Marseille, France; the Department of Angiology (A.M.), University Medical Centre, Ljubljana, Slovenia; the Department of Gastric Surgery (B.B.), CHU Timone, Marseille, France; the Service d'Endocrinologie (M.G.), Maladies Métaboliques et Nutrition, CHU Nord, Marseille, France; and the Centre d'Investigation Clinique (M.-C.A., P.M., I.J.-V.), AP-HM INSERM 95[hyphen]02, Hôpital Ste. Marguerite, Marseille, France.
* To whom correspondence should be addressed. E-mail: Marie-Christine.Alessi{at}medecine.univ-mrs.fr..
Objective--Because obesity and insulin resistance (IR) are strongly associated with liver steatosis (LS), we investigated the relation between the degree of LS and plasminogen activator inhibitor-1 (PAI-1) in ob/ob mice, in C57/BL6 mice with alcoholic LS, and in severely obese humans.
Methods and Results--In both mouse models, plasma PAI-1 levels were associated with PAI-1 expression in the liver and with the degree of LS. Liver PAI-1 antigen was associated with the tumor necrosis factor receptor-II (TNFRII) antigen, whereas association with TNF antigen content was found in ob/ob mice only. No significant correlation between plasma PAI-1 and PAI-1 expression in adipose tissue of ob/ob mice was observed. Furthermore, the relation between plasma PAI-1 levels and body weight was positive in ob/ob mice but negative in C57/BL6 mice (both P<0.001). In humans, PAI-1 levels were correlated with the degree of LS, and 26% of plasma PAI-1 activity was independently explained by LS and serum insulin levels.
Conclusions--Plasma PAI-1 levels are more closely related to fat accumulation and PAI-1 expression in the liver than in adipose tissue. In steatotic liver, PAI-1 antigen content is associated with those of TNF and TNFRII. Therefore, we suggest that TNF pathway dysregulation in LS could be involved in increased plasma PAI-1 in obesity with IR.
Key words: liver steatosis • PAI-1 • adipose tissue • insulin resistance
This article has been cited by other articles:
 |
|
 |
|
  R. Serrano, J. Barrenetxe, J. Orbe, J. A. Rodriguez, N. Gallardo, C. Martinez, A. Andres, and J. A. Paramo Tissue-specific PAI-1 gene expression and glycosylation pattern in insulin-resistant old rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1563 - R1569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bortolotti, R. Kreis, C. Debard, B. Cariou, D. Faeh, M. Chetiveaux, M. Ith, P. Vermathen, N. Stefanoni, K.-A. Le, et al. High protein intake reduces intrahepatocellular lipid deposition in humans Am. J. Clinical Nutrition, October 1, 2009; 90(4): 1002 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Oishi, D. Uchida, N. Ohkura, R. Doi, N. Ishida, K. Kadota, and S. Horie Ketogenic Diet Disrupts the Circadian Clock and Increases Hypofibrinolytic Risk by Inducing Expression of Plasminogen Activator Inhibitor-1 Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1571 - 1577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Thuy, R. Ladurner, V. Volynets, S. Wagner, S. Strahl, A. Konigsrainer, K.-P. Maier, S. C. Bischoff, and I. Bergheim Nonalcoholic Fatty Liver Disease in Humans Is Associated with Increased Plasma Endotoxin and Plasminogen Activator Inhibitor 1 Concentrations and with Fructose Intake J. Nutr., August 1, 2008; 138(8): 1452 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Targher, M. Chonchol, L. Bertolini, S. Rodella, L. Zenari, G. Lippi, M. Franchini, G. Zoppini, and M. Muggeo Increased Risk of CKD among Type 2 Diabetics with Nonalcoholic Fatty Liver Disease J. Am. Soc. Nephrol., August 1, 2008; 19(8): 1564 - 1570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. de Larranaga, S. P. Wingeyer, M. Graffigna, S. Belli, K. Bendezu, S. Alvarez, O. Levalle, and H. Fainboim Plasma Plasminogen Activator Inhibitor-1 Levels and Nonalcoholic Fatty Liver in Individuals With Features of Metabolic Syndrome Clinical and Applied Thrombosis/Hemostasis, July 1, 2008; 14(3): 319 - 324. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Sozio and D. W. Crabb Alcohol and lipid metabolism Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E10 - E16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boullu-Ciocca, V. Achard, V. Tassistro, A. Dutour, and M. Grino Postnatal Programming of Glucocorticoid Metabolism in Rats Modulates High-Fat Diet-Induced Regulation of Visceral Adipose Tissue Glucocorticoid Exposure and Sensitivity and Adiponectin and Proinflammatory Adipokines Gene Expression in Adulthood Diabetes, March 1, 2008; 57(3): 669 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Westerbacka, M. Kolak, T. Kiviluoto, P. Arkkila, J. Siren, A. Hamsten, R. M. Fisher, and H. Yki-Jarvinen Genes Involved in Fatty Acid Partitioning and Binding, Lipolysis, Monocyte/Macrophage Recruitment, and Inflammation Are Overexpressed in the Human Fatty Liver of Insulin-Resistant Subjects Diabetes, November 1, 2007; 56(11): 2759 - 2765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Targher, L. Bertolini, L. Scala, L. Zenari, G. Lippi, M. Franchini, and G. Arcaro Plasma PAI-1 Levels Are Increased in Patients With Nonalcoholic Steatohepatitis Diabetes Care, May 1, 2007; 30(5): e31 - e32. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Dentali, E. Romualdi, and W. Ageno The metabolic syndrome and the risk of thrombosis Haematologica, March 1, 2007; 92(3): 297 - 299. [Full Text] [PDF]
|
|
|
|
|
|
S. Imagawa, S. Fujii, J. Dong, T. Furumoto, T. Kaneko, T. Zaman, Y. Satoh, H. Tsutsui, and B. E Sobel Hepatocyte Growth Factor Regulates E Box-Dependent Plasminogen Activator Inhibitor Type 1 Gene Expression in HepG2 Liver Cells Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2407 - 2413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-C. Alessi and I. Juhan-Vague PAI-1 and the Metabolic Syndrome: Links, Causes, and Consequences Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2200 - 2207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Klover, A. H. Clementi, and R. A. Mooney Interleukin-6 Depletion Selectively Improves Hepatic Insulin Action in Obesity Endocrinology, August 1, 2005; 146(8): 3417 - 3427. [Abstract] [Full Text] [PDF]
|
|