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Publication
Bone marrow plasminogen activator inhibitor-1 influences the development of
obesity.
Authors De Taeye BM, Novitskaya T, Gleaves L, Covington JW, Vaughan DE
Submitted By Douglas Vaughan on 11/6/2007
Status Published
Journal The Journal of biological chemistry
Year 2006
Date Published
Volume : Pages 281 : 32796 - 32805
PubMed Reference 16931518
Abstract Plasma levels of plasminogen activator inhibitor-1 (PAI-1) are elevated in
obesity and correlate with body mass index. The increase in PAI-1 associated
with obesity likely contributes to increased cardiovascular risk and may predict
the development of type 2 diabetes mellitus. Although adipocytes are capable of
synthesizing PAI-1, the bulk of evidence indicates that cells residing in the
stromal fraction of visceral fat are the primary source of PAI-1. We
hypothesized that bone marrow-derived PAI-1, e.g. derived from macrophages
located in visceral fat, contributes to the development of diet-induced obesity.
To test this hypothesis, male C57BL/6 wild-type mice and C57BL/6 PAI-1 deficient
mice were transplanted with either PAI-1(-/-), PAI-1(+/-), or PAI-1(+/+) bone
marrow. The transplanted animals were subsequently fed a high fat diet for 24
weeks. Our findings show that only the complete absence of PAI-1 protects from
the development of diet-induced obesity, whereas the absence of bone
marrow-derived PAI-1 protects against expansion of the visceral fat mass.
Remarkably, there is a link between the PAI-1 levels, the degree of inflammation
in adipose tissue, and the development of obesity. Based on these findings we
suggest that bone marrow-derived PAI-1 has an effect on the development of
obesity through its effect on inflammation.






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