Adipose tissue secretion of plasminogen activator inhibitor-1 in non-obese and obese individuals.
High plasma plasminogen activator inhibitor-1 (PAI-1) activity is a frequent finding in obesity, and both PAI-1 and obesity are risk factors for cardiovascular disease. To study the mechanisms underlying increased PAI-1 levels in obese individuals, gene expression and secretion of PAI-1 were measured in human abdominal subcutaneous adipose tissue. A total of 32 obese, otherwise healthy subjects and 10 never-obese healthy subjects with a body mass index (BMI) of 42.6 +/- 1.2 and 24.3 +/- 1.9 kg/m2 (mean +/- SEM), respectively, were investigated. Plasma PAI-1 activity, adipose tissue PAI-1 secretion and adipocyte PAI-1 mRNA levels were increased seven-fold (p < 0.0001), sixfold (p < 0.0001) and twofold (p < 0.05), respectively, in the obese group. There were clear associations between adipose tissue secretion of PAI-1 and PAI-1 mRNA levels on the one hand and fat cell volume on the other (r = 0.68, p < 0.0001 and r = 0.51, p < 0.01, respectively, in the obese group). PAI-1 mRNA levels were also related to the amount of PAI-1 secreted among obese individuals (r = 0.31, p = 0.09). It is concluded that adipose tissue secretes significant amounts of PAI-1, that PAI-1 secretion from adipose tissue is increased in obesity, and that PAI-1 secretion is related to the lipid content and cell volume of fat cells. Plasma PAI-1 activity is elevated in obesity, at least in part due to increased gene expression in adipocytes, which, in turn, enhances PAI-1 secretion from adipose tissue.
Eriksson
P
P
Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institute, Stockholm, Sweden.
Reynisdottir
S
S
Lönnqvist
F
F
Stemme
V
V
Hamsten
A
A
Arner
P
P
D000273:Adipose Tissue / Q000378:metabolism* / Q000601:surgery; D001786:Blood Glucose / Q000378:metabolism; D001824:Body Constitution; D015992:Body Mass Index; D001835:Body Weight; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D009765:Obesity / Q000378:metabolism* / Q000601:surgery; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012016:Reference Values; D014158:Transcription, Genetic; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014280:Triglycerides