title: Bone marrow plasminogen activator inhibitor-1 influences the development of obesity.
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.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University, 2220 Pierce Avenue, Nashville, TN 37232, USA.
authors.forename: Bart M
authors.initials: BM
authors.lastname: De Taeye
authors.forename: Tatiana
authors.initials: T
authors.lastname: Novitskaya
authors.forename: Linda
authors.initials: L
authors.lastname: Gleaves
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Covington
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vaughan
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D001853:Bone Marrow / Q000737:chemistry*; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D004041:Dietary Fats / Q000008:administration & dosage; D004734:Energy Metabolism; D005215:Fasting; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009043:Motor Activity; D009765:Obesity / Q000097:blood* / Q000378:metabolism*; D009929:Organ Size; D010101:Oxygen Consumption; D017395:Plasminogen Activator Inhibitor 1 / Q000172:deficiency / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D052243:Resistin / Q000097:blood; D013997:Time Factors
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D052243:Resistin