Serine protease inhibitor from the muscle larval Trichinella spiralis ameliorates non-alcoholic fatty liver disease in mice via anti-inflammatory properties and gut-liver crosstalk - 29/02/24
Abstract |
Trichinella spiralis is recognized for its ability to regulate host immune responses. The serine protease inhibitor of T. spiralis (Ts-SPI) participates in T. spiralis-mediated immunoregulatory effects. Studies have shown that helminth therapy exhibits therapeutic effects on metabolic diseases. In addition, we previously found that T. spiralis-derived crude antigens could alleviate diet-induced obesity. Thus, Ts-SPI was hypothesized to alleviate non-alcoholic fatty liver disease (NAFLD). Herein, recombinant Ts-SPI (rTs-SPI) was prepared from the muscle larvae T. spiralis. The relative molecular mass of rTs-SPI was approximately 35,000 Da, and western blot analysis indicated good immunoreactivity. rTs-SPI ameliorated hepatic steatosis, inflammation, and pyroptosis in NAFLD mice, which validated the hypothesis. rTs-SPI also reduced macrophage infiltration, significantly expanded Foxp3+ Treg population, and inactivated TLR4/NF-κB/NLRP3 signaling in the liver. Furthermore, rTs-SPI treatment significantly shifted the gut microbiome structure, with a remarkable increase in beneficial bacteria and reduction in harmful bacteria to improve gut barrier integrity. Finally, Abx-treated mice and FMT confirmed that gut-liver crosstalk contributed to NAFLD improvement after rTs-SPI treatment. Taken together, Taken together, these findings suggest that rTs-SPI exerts therapeutic effects in NAFLD via anti-inflammatory activity and gut–liver crosstalk.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Purification and characterization of recombinant serine protease inhibitor of T. spiralis (rTs-SPI). |
• | rTs-SPI alleviates NAFLD in mice. |
• | rTs-SPI exhibits anti-inflammatory action and inactivates the TLR4/NF-κB/NLRP3 signaling. |
• | rTs-SPI restores the gut dysbiosis and the fecal microbiota transplantation (FMT) trial is effective in ameliorating NAFLD. |
Keywords : Trichinella spiralis serine protease inhibitor, Non-alcoholic fatty liver disease, Gut-liver crosstalk, Inflammation, TLR4/NF-κB/NLRP3 signaling
Plan
Vol 172
Article 116223- mars 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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