Plasminogen activator inhibitor-1, adipose tissue and insulin resistance.
OBJECTIVE
Plasminogen activator inhibitor (PAI)-1 is a physiological inhibitor of plasminogen activators (urokinase and tissue types) and vitronectin. It is synthesized by adipose tissue, and its levels in plasma are increased in obesity and reduced with weight loss. Circulating PAI-1 level predicts development of type 2 diabetes, suggesting that it may be causally related to development of obesity. A role for PAI-1 in development of obesity has only partially been established, however. This review summarizes current knowledge, gives context to developments thus far and discusses controversies.


RESULTS
In addition to its role in atherothrombosis, PAI-1 might be involved in adipose tissue development. PAI-1 is produced by ectopic fat depots under the influence of inducers. Among the most recently described inducers are inflammation, oxidative stress and circadian clock protein. PAI-1 may play several roles in contributing to obesity: through indirect effects on insulin signalling, by influencing adipocyte differentiation and by regulating recruitment of inflammatory cells within adipose tissue.


CONCLUSIONS
These recent findings emphasize the involvement of PAI-1 in controlling the biology of adipose tissue; PAI-1 is an attractive new therapeutic target to retard the metabolic complications that accompany obesity.
Alessi
Marie-Christine
MC
Laboratoire d'hématologie-Inserm UMR 626, Faculty of Medicine, Marseilles, France. marie-christine.alessi@medecine.univ-mrs.fr
Poggi
Marjorie
M
Juhan-Vague
Irène
I
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002940:Circadian Rhythm; D006801:Humans; D007249:Inflammation; D007333:Insulin Resistance; D008233:Lymphotoxin-alpha / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D008233:Lymphotoxin-alpha; D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator