Extracellular vesicles from periodontal pathogens regulate hepatic steatosis via Toll‐like receptor 2 and plasminogen activator inhibitor‐1

• Published in: Journal of extracellular vesicles Vol. 13; no. 1; pp. e12407 - n/a
• Main Authors: Kim, Hyun Young, Lim, Younggap, Jang, Ji Sun, Ko, Yeon Kyeong, Choi, Youngnim, Kim, Hong‐Hee, Choi, Bong‐Kyu
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2024; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Bacteria; Carbohydrates; Correlation analysis; Diabetes; Diet; Enzymes; extracellular vesicle; Extracellular Vesicles; Fatty liver; Gram-positive bacteria; Gum disease; Humans; Lipids; Liver diseases; Low fat diet; Metabolic syndrome; Mice; Microbiota; Non-alcoholic Fatty Liver Disease; nonalcoholic fatty liver disease; Nutrient deficiency; Pathogens; periodontal pathogen; Plasminogen Activator Inhibitor 1; Plasminogen activator inhibitors; Review boards; Risk factors; Steatosis; TLR2 protein; Toll-Like Receptor 2; Toll-like receptors; United States > US; South Korea; nonalcoholic fatty liver disease; periodontal pathogen; plasminogen activator inhibitor-1; Toll-like receptor 2; extracellular vesicle
• ISSN: 2001-3078; 2001-3078
• DOI: 10.1002/jev2.12407

Plasminogen activator inhibitor‐1 (PAI‐1) is associated with nonalcoholic fatty liver disease (NAFLD) by lipid accumulation in the liver. In this study, we showed that extracellular vesicles (EVs) from the periodontal pathogens Filifactor alocis and Porphyromonas gingivalis induced steatosis by inducing PAI‐1 in the liver and serum of mice fed a low‐fat diet. PAI‐1 induction was not observed in TLR2−/− mice. When tested using HEK‐Blue hTLR2 cells, human TLR2 reporter cells, the TLR2‐activating ability of serum from NAFLD patients (n = 100) was significantly higher than that of serum from healthy subjects (n = 100). Correlation analysis confirmed that PAI‐1 levels were positively correlated with the TLR2‐activating ability of serum from NAFLD patients and healthy subjects. Amphiphilic molecules in EVs were involved in PAI‐1 induction. Our data demonstrate that the TLR2/PAI‐1 axis is important for hepatic steatosis by EVs of periodontal pathogens.