Published online before print May 15, 2003, doi: 10.1161/01.ATV.0000077401.36885.BB
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© 2003 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Plasma PAI-1 Levels Are More Strongly Related to Liver Steatosis Than to Adipose Tissue Accumulation
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 95-02, Hôpital Ste. Marguerite, Marseille, France.
Correspondence to Pr M.C. Alessi, Laboratoire d’Hématologie, EPI 9936, 27, Bd Jean Moulin, 13385 Marseille Cedex 5, France. 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
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