Plasma PAI-1 levels are more strongly related to liver steatosis than to adipose tissue accumulation.
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.


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.
Alessi
Marie-Christine
MC
Laboratoire d'Hématologie, EPI 99-36, 27, Faculty of Medicine, Bd Jean Moulin, 13385 Marseille Cedex 5, France. Marie-Christine.Alessi@medecine.univ-mrs.fr.
Bastelica
Delphine
D
Mavri
Alenka
A
Morange
Pierre
P
Berthet
Bruno
B
Grino
Michel
M
Juhan-Vague
Irene
I
D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D005234:Fatty Liver / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D009767:Obesity, Morbid / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D047889:Receptors, Tumor Necrosis Factor, Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015703:Antigens, CD; D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha