Bone marrow plasminogen activator inhibitor-1 influences the development of obesity
Autor: | Joseph W. Covington, Tatiana Novitskaya, Douglas E. Vaughan, Bart De Taeye, Linda A. Gleaves |
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Rok vydání: | 2006 |
Předmět: |
Blood Glucose
Leptin medicine.medical_specialty Stromal cell Time Factors Adipose tissue Bone Marrow Cells Mice Transgenic Motor Activity Biochemistry chemistry.chemical_compound Mice Oxygen Consumption Bone Marrow Internal medicine Plasminogen Activator Inhibitor 1 medicine Animals Insulin Resistin Obesity RNA Messenger Molecular Biology Bone Marrow Transplantation Mice Knockout Adiponectin business.industry Cell Biology Fasting Organ Size Glucose Tolerance Test Dietary Fats Mice Inbred C57BL medicine.anatomical_structure Endocrinology chemistry Adipose Tissue Plasminogen activator inhibitor-1 Body Composition Bone marrow business Energy Metabolism Plasminogen activator |
Zdroj: | The Journal of biological chemistry. 281(43) |
ISSN: | 0021-9258 |
Popis: | 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. |
Databáze: | OpenAIRE |
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