PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
Authors: Brock A Humphries; Johanna M Buschhaus; Yu-Chih Chen; Henry R Haley; Tonela Qyli; Benjamin Chiang; Nathan Shen; Shrila Rajendran; Alyssa Cutter; Yu-Heng Cheng; Yu-Ting Chen; Jason Cong; Phillip C Spinosa; Euisik Yoon; Kathryn E Luker; Gary D Luker Journal: Mol Cancer Res Date: 2019-02-04 Impact factor: 5.852
Authors: Carrie M Elks; Peng Zhao; Ryan W Grant; Hardy Hang; Jennifer L Bailey; David H Burk; Margaret A McNulty; Randall L Mynatt; Jacqueline M Stephens Journal: J Biol Chem Date: 2016-06-20 Impact factor: 5.157
Authors: Rachel C Masters; Angela D Liese; Steven M Haffner; Lynne E Wagenknecht; Anthony J Hanley Journal: J Nutr Date: 2010-01-20 Impact factor: 4.798
Authors: Nino G Joy; Jennifer M Perkins; Maia Mikeladze; Lisa Younk; Donna B Tate; Stephen N Davis Journal: J Diabetes Complications Date: 2016-07-04 Impact factor: 2.852
Authors: David Sanchez-Infantes; Ursula A White; Carrie M Elks; Ron F Morrison; Jeffrey M Gimble; Robert V Considine; Anthony W Ferrante; Eric Ravussin; Jacqueline M Stephens Journal: J Clin Endocrinol Metab Date: 2013-12-02 Impact factor: 5.958