PAI-1 Exacerbates White Adipose Tissue Dysfunction and Metabolic Dysregulation in High Fat Diet-Induced Obesity
Background: Plasminogen activator inhibitor (PAI)-1 levels and activity are recognized to increase during metabolic syndrome and weight problems. Additionally, previous research has implicated PAI-one in adipose tissue (AT) expansion whilst adding to insulin resistance. As inflammation is known to exist in AT during weight problems, we hypothesized that inside a high-fat diet (HFD)-caused obese mouse model PAI-1 plays a role in macrophage-mediated inflammation and metabolic disorder. Methods: Four- to 5-days-old male C57B6/6J rodents were given a HFD (45%) for 14 days, while age-matched control rodents were given a typical laboratory chow diet (10% fat). Additional studies were performed in PAI-1 knockout rodents and wild type rodents given an inhibitor (PAI-039) of PAI-1. Macrophage polarization were measured by real-time PCR. Results: HFD rodents demonstrated elevated expression of PAI-one in visceral white-colored AT (WAT) which displayed elevated macrophage figures. PAI-1 deficient rodents exhibited elevated figures of anti-inflammatory macrophages in WAT and were resistant against HFD-caused weight problems. Similarly, medicinal inhibition of PAI-1 using PAI-039 considerably decreased macrophage infiltration in WAT and improved metabolic status in HFD-caused wild-type rodents. Importantly, the figures of M1 macrophages made an appearance to become elevated through the HFD and decreased by genetic PAI-1 depletion or PAI-039 treatment. Conclusions: With each other, our findings provide support for PAI-1 adding to the introduction of inflammation in adipose tissue and explain the mechanism of PAI-039 inflammation modulated by PAI-one in the disordered metabolic process in HFD-caused weight problems.