FNDC5/Irisin Inhibits the Inflammatory Response and Mediates the Aerobic Exercise-Induced Improvement of Liver Injury after Myocardial Infarction

Abstract

Myocardial infarction (MI) causes peripheral organ injury, in addition to cardiac dysfunction, including in the liver, which is known as cardiac hepatopathy. Aerobic exercise (AE) can effectively improve liver injury, although the mechanism and targets are currently not well established. Irisin, mainly produced by cleavage of the fibronectin type III domain-containing protein 5 (FNDC5), is a responsible for the beneficial effects of exercise training. In this study, we detected the effect of AE on MI-induced liver injury and explored the role of irisin alongside the benefits of AE. Wildtype and Fndc5 knockout mice were used to establish an MI model and subjected to AE intervention. Primary mouse hepatocytes were treated with lipopolysaccharide (LPS), rhirisin, and a phosphoinositide 3-kinase (PI3K) inhibitor. The results showed that AE significantly promoted M2 polarization of macrophages and improved MI-induced inflammation, upregulated endogenous irisin protein expression and activated the PI3K/ protein kinase B (Akt) signaling pathway in the liver of MI mice, while knockout of Fndc5 attenuated the beneficial effects of AE. Exogenous rhirisin significantly inhibited the LPS-induced inflammatory response, which was attenuated by the PI3K inhibitor. These results suggest that AE could effectively activate the FNDC5/irisin-PI3K/Akt signaling pathway, promote the polarization of M2 macrophages, and inhibit the inflammatory response of the liver after MI.

Aerobic exercise attenuates LPS-induced cognitive dysfunction by reducing oxidative stress, glial activation, and neuroinflammation

“…This regional specificity demonstrates the relevance and effectiveness of the aerobic exercise. Moreover, consistent with an earlier report [ 28 ], the expressions of FNDC5/irisin and BDNF in the brain were higher in the aerobic exercise group than in the LPS group. These findings suggest that aerobic exercise (5 days/week for 4 weeks at a speed of 10 rpm/min) plays a neuroprotective role against LPS-induced neurotoxicity and effectively attenuates LPS-induced spatial learning and memory impairments by promoting the BDNF/FNDC5/CREB pathway.…”

Potential role of irisin in lung diseases and advances in research

“…In addition, irisininduced M2 polarization enhances osteogenesis in osteoblasts, an effect that may be related to AMPK activation (Ye et al, 2020). Moreover, aerobic exercise can effectively activate the FNDC5/irisin and PI3K/AKT signaling pathways, promote the polarization of M2 macrophages, and inhibit the inflammatory response of the liver after myocardial infarction (Wang et al, 2023). In mice, irisin administration following LPS stimulation leads to inhibition of M1 polarization and promotion of M2 polarization, thus reducing LPS-induced production and secretion of IL-1β, IL-18, and TNF-α, resulting in anti-inflammatory activity and reduced alveolar inflammatory cell infiltration .…”