| First Author | Samad F | Year | 2022 |
| Journal | J Thromb Haemost | Volume | 20 |
| Issue | 3 | Pages | 742-754 |
| PubMed ID | 34897983 | Mgi Jnum | J:348778 |
| Mgi Id | MGI:7643992 | Doi | 10.1111/jth.15622 |
| Citation | Samad F, et al. (2022) The plasminogen receptor Plg-R(KT) regulates adipose function and metabolic homeostasis. J Thromb Haemost 20(3):742-754 |
| abstractText | 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-R(KT) 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-R(KT) . Mice genetically deficient in Plg-R(KT) and littermate controls fed a HFD or control low fat diet (LFD) were used to determine the role of Plg-R(KT) in insulin resistance, glucose tolerance, type 2 diabetes, and associated mechanisms including adipose inflammation, fibrosis, and ectopic lipid storage. The role of Plg-R(KT) in adipogenesis was determined using 3T3-L1 preadipocytes and primary cultures established from Plg-R(KT) -deficient and littermate control mice. RESULTS: Plg-R(KT) was highly expressed in both human and mouse AT, and its levels dramatically increased during adipogenesis. Plg-R(KT) -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-R(KT) regulated the expression of PPARgamma and other adipogenic molecules, suggesting a novel role for Plg-R(KT) in the adipogenic program. CONCLUSIONS: Plg-R(KT) coordinately regulates multiple aspects of adipose function that are important to maintain efficient metabolic homeostasis. |
