Review Article

Antioxidant Effects of Irisin in Liver Diseases: Mechanistic Insights

Table 1

The main mechanism of antioxidant effects of irisin.

StudyCrucial moleculesLiver disease1Animal modelsResults

Bi et al. [14], 2019UCP-2HIRC57BL/6J mice2Irisin could suppress the production of ROS via upregulating UCP-2.
Bi et al. [14], 2019Drp-1, Fis-1HIRC57BL/6J miceIrisin could decrease the expression of Drp-1 and Fis-1 to inhibit inappropriate mitochondrial fission for less oxidative stress.
Bi et al.[14], 2019PGC-1a, TFAMHIRC57BL/6J miceIrisin might increase the level of the PGC-1a and TFAM to decrease the oxidative stress by promoting mitochondrial biogenesis.
Park et al. [62], 2015PRMT3NAFLDAML12 cells3/mouse primary hepatocytesIrisin may attenuate the function of PRMT3 to decrease the production of ROS.
Fan et al. [27], 2019NLRP3 inflammasomesLiver fibrosisAdult male Sprague-Dawley ratsIrisin may inhibit the formation of the NLRP3 inflammasomes to reduce the hepatic injury due to oxidative stress.
Bi et al. [13], 2020JNK, telomeraseHIRMale Sprague-Dawley ratsIrisin would elevate the function of telomerase to promote the autophagy of hepatocyte to reduce the production of ROS via inhibiting JNK phosphorylation.
Zhang et al. [36], 2020Kindlin-2, αv integrinsHIRC57BL/6J miceKindlin-2 may participate in the antioxidant effects of irisin.
The αv integrins are transmembrane receptor of irisin to exert irisin’s antioxidant effect.
Mazur-Bialy and Pocheć [71], 2021Nrf2, HO-1NAFLDQuiescent macrophages/LPS-stimulated macrophagesIrisin reduces oxidative stress via Nrf2/HO-1 involved pathway.
Li et al. [89], 2021SIRT2NAFLDC57BL/6J miceSIRT2 might maintain the stability of irisin to perform antioxidant function.
Wei et al. [86], 2020GPX4Liver in sepsisC57BL/6J miceGPX4 is involved in the antioxidant effect of irisin and mitigates the ferroptosis.

1The liver disease models established in the experiment or involved in relevant pathways. 2C57BL/6J mice is the most used inbred strain of laboratory mouse. 3AML12 cells were established from hepatocytes from a transgenic mouse with human TGF-α. ROS: reactive oxygen species; NAFLD: nonalcoholic fatty liver disease; HIR: hepatic ischemia reperfusion injury; SOD: superoxide dismutase; UCP-2: Uncoupling protein-2; Drp1: Dynamin-related protein 1; Fis1: fission protein 1; PGC-1a: peroxisome proliferator–activated receptor gamma coactivator-1 alpha; TFAM: mitochondrial transcription factor A; PRMTs: protein arginine methyltransferases; NLRP3: nucleotide-binding oligomerization domain-like receptor 3; TERT: telomerase reverse transcriptase; JNK: c-Jun NH2-terminal kinase; Nrf2: nuclear factor erythroid 2-related factor 2; HO-1: heme oxygenase 1; LPS: lipopolysaccharide; GPX-4: glutathione peroxidase-4; SIRT2: Sirtuin 2.