1. The plasminogen receptor Plg-R KT regulates adipose function and metabolic homeostasis.
- Author
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Samad F, Bai H, Baik N, Haider P, Zhang Y, Rega-Kaun G, Kaun C, Prager M, Wojta J, Bui Q, Chakrabarty S, Wang J, Parmer RJ, and Miles LA
- Subjects
- Animals, Diabetes Mellitus, Type 2 metabolism, Dietary Fats pharmacology, Fibrosis, Glucose Tolerance Test, Humans, Inflammation metabolism, Insulin Resistance, Mice, Plasminogen metabolism, Adipose Tissue metabolism, Homeostasis, Receptors, Cell Surface metabolism
- Abstract
Background: Plg-R
KT , a unique transmembrane plasminogen receptor, enhances the activation of plasminogen to plasmin, and localizes the proteolytic activity of plasmin on the cell surface., Objectives: We investigated the role of Plg-RKT in adipose function, metabolic homeostasis, and obesity., Methods: We used adipose tissue (AT) sections from bariatric surgery patients and from high fat diet (HFD)-induced obese mice together with immunofluorescence and real-time polymerase chain reaction to study adipose expression of Plg-RKT . Mice genetically deficient in Plg-RKT and littermate controls fed a HFD or control low fat diet (LFD) were used to determine the role of Plg-RKT in insulin resistance, glucose tolerance, type 2 diabetes, and associated mechanisms including adipose inflammation, fibrosis, and ectopic lipid storage. The role of Plg-RKT in adipogenesis was determined using 3T3-L1 preadipocytes and primary cultures established from Plg-RKT -deficient and littermate control mice., Results: Plg-RKT was highly expressed in both human and mouse AT, and its levels dramatically increased during adipogenesis. Plg-RKT -deficient mice, when fed a HFD, gained more weight, developed more hepatic steatosis, and were more insulin resistant/glucose intolerant than HFD-fed wild-type littermates. Mechanistically, these metabolic defects were linked with increased AT inflammation, AT macrophage and T-cell accumulation, adipose and hepatic fibrosis, and decreased insulin signaling in the AT and liver. Moreover, Plg-RKT regulated the expression of PPARγ and other adipogenic molecules, suggesting a novel role for Plg-RKT in the adipogenic program., Conclusions: Plg-RKT coordinately regulates multiple aspects of adipose function that are important to maintain efficient metabolic homeostasis., (© 2021 International Society on Thrombosis and Haemostasis.)- Published
- 2022
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