Irisin alleviates LPS-induced liver injury and inflammation through inhibition of NLRP3 inflammasome and NF-κB signaling

Abstract

Lipopolysaccharide (LPS) provokes severe inflammation and cell death in sepsis, with liver being the major affected organ. Up-to-date, neither the mechanism of action nor target treatment is readily available for LPS-induced liver injury. This study examined the effect of irisin, an endogenous hormonal peptide, on LPS-induced liver injury using animal and cell models, and the mechanism involved with a special focus on pyroptosis. Irisin is known to regulate glucose metabolism, inflammation, and immune response, while our earlier work denoted the anti-inflammatory and anti-apoptotic properties for irisin. Inflammatory factors and AST/ALT were also detected. Pyroptosis, apoptosis, and reactive oxygen species (ROS) were evaluated using PI staining, TUNEL staining, DCFH-DA fluorescence, and western blot, respectively. Our results indicated that irisin attenuated LPS-induced liver injury and release of inflammatory cytokines. Increased activity of NLRP3 inflammasome was discovered in LPS-challenged Raw264.7 cells, along with elevated levels of inflammation and apoptosis, the effects of which were mediated by activation of ROS and nuclear factor κB (NF-κB) signaling. These changes were reversed following irisin treatment. Our study demonstrated that irisin countered LPS-mediated liver injury via inhibiting apoptosis, NLRP3 inflammasome activation and NF-κB signaling. These findings revealed the role of irisin as a promising new anti-pyroptosis/apoptosis agent to reconcile the onset and progression of septic liver injury.

Keywords:

• Irisin
• inflammation
• LPS
• macrophage
• pyroptosis
• septic liver injury

Acknowledgments

We thank the Freescience editorial team for the excellent language assistance.

Author contribution(s)

QL participated in the design of experiments and manuscript preparation. YT, SC, XX, MZ and QW helped with assays and analyses. MD supervised processes of experiments and manuscript preparation. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the National Nature Science Foundation of China [No.81571895 and 81372055] and the Natural Science Foundation of Guangdong Province, China [No. 2019A1515010944].