title: The fat mouse: a powerful genetic model to study elevated plasminogen activator inhibitor 1 in obesity/NIDDM.
abstract: Plasminogen activator inhibitor-1 is elevated in obesity and may be a risk factor for obesity/NIDDM related cardiovascular disease. In spite of this, little is known about the tissue and cellular origin of elevated PAI-1 in obesity or of the mediators and molecular mechanisms that regulate it. We have begun to systematically address these issues using genetically obese (ob/ob, db/db) mice. Plasma PAI-1 levels were 5-fold higher in obese mice compared to their lean counterparts. Subsequent RT-PCR and in situ hybridization studies suggest that the increased plasma PAI-1 originates primarily from the adipocyte in response to chronically elevated levels of tumor necrosis factor-alpha (TNF-alpha), insulin, and transforming growth factor-beta (TGF-beta). Thus, the signals and mechanisms that lead to elevated plasma PAI-1 observed in obesity are complex, and appear to involve interactions between multiple mediators and the adipose tissue itself.
authors.affiliation: Department of Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: F
authors.initials: F
authors.lastname: Samad
authors.forename: D J
authors.initials: DJ
authors.lastname: Loskutoff
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000097:blood* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics; D006801:Humans; D051379:Mice; D008820:Mice, Obese; D008957:Models, Genetic; D009765:Obesity; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha