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

Li, Qian; Tan, Ying; Chen, Sainan; Xiao, Xiaochan; Zhang, Mingming; Wu, Qi; Dong, Maolong

doi:10.1080/10799893.2020.1808675

Cited by 70 publications

(45 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Irisin was previously reported to exert anti-inflammatory effects in LPS-stimulated liver injury [ 32 ]. Hence, we hypothesized that irisin could mediate the anti-inflammatory role of exercise in regulating HFD-induced NAFLD.…”

Section: Resultsmentioning

confidence: 99%

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Zhu

Sahar

Javaid

et al. 2021

Cells

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is a global clinical problem. The MD2-TLR4 pathway exacerbates NAFLD progression by promoting inflammation. Long-term exercise is considered to improve NAFLD but the underlying mechanism is still unclear. In this study, we examined the protective effect and molecular mechanism of exercise on high-fat diet (HFD)-induced liver injury. In an HFD-induced NAFLD mouse model, exercise training significantly decreased hepatic steatosis and fibrosis. Interestingly, exercise training blocked the binding of MD2-TLR4 and decreased the downstream inflammatory response. Irisin is a myokine that is highly expressed in response to exercise and exerts anti-inflammatory effects. We found that circulating irisin levels and muscle irisin expression were significantly increased in exercised mice, suggesting that irisin could mediate the effect of exercise on NAFLD. In vitro studies showed that irisin improved lipid metabolism, fibrosis, and inflammation in palmitic acid (PA)-stimulated AML12 cells. Moreover, binding assay results showed that irisin disturbed MD2-TLR4 complex formation by directly binding with MD2 but not TLR4, and interfered with the recognition of stimuli such as PA and lipopolysaccharide with MD2. Our study provides novel evidence that exercise-induced irisin inhibits inflammation via competitive binding with MD2 to improve NAFLD. Thus, irisin could be considered a potential therapy for NAFLD.

show abstract

Section: Resultsmentioning

confidence: 99%

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Zhu

Sahar

Javaid

et al. 2021

Cells

View full text Add to dashboard Cite

show abstract

“…Interestingly, recent research found that traditional Chinese treatment electrical auricular acupuncture (EAA) could also reduce body weight and suppress inflammation through promoting norepinephrine (NE) release from the adrenal gland leading to further expression of FNDC5, irisin, and UCP-1 [98]. In addition to adipocytes and macrophages, irisin is also involved in the anti-inflammatory effects of other tissues and organs [99][100][101][102][103][104][105][106][107][108][109][110][111], as shown in Table 1.…”

Section: Anti-inflammatory Effects Of Irisinmentioning

confidence: 99%

“…Liver injury [111] LPS-mediated liver injury IL-6, IL-1β, TNF-α, and NF-κB↓ LPS, lipopolysaccharide; TNF-α, tumor necrosis factor α; IL-6, interleukin 6; MCP-1, monocyte chemotactic protein 1; NF-κB, nuclear factor-κB; IL-1β, interleukin 1β; KC, keratinocyte chemoattractant; HMGB1, high mobility group box 1; COX2, cyclooxygenase-2; CCL2, chemokine (C-C motif ) ligand 2; CXCL1, chemokine (C-X-C motif) ligand 1; ICAM-1, intercellular cell adhesion molecule-1; VCAM-1, vascular cell adhesion protein 1; ALI, acute lung injury; MAPK, mitogen-activated protein kinase; IBDs, inflammatory bowel diseases; TNBS, 2,4,6-trinitrobenzenesulfonic acid; DSS, dextran sodium sulfate; PA, palmitic acid; PRMT3, protein arginine methyltransferase-3.…”

Section: Study (Reference)mentioning

confidence: 99%

The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity

Wang

Yang

et al. 2021

International Journal of Endocrinology

View full text Add to dashboard Cite

Obesity is a worldwide health problem due to the imbalance of energy intake and energy expenditure. Irisin, a newly identified exercise-responsive myokine, which is produced by the proteolytic cleavage of fibronectin type III domain-containing protein 5 (FNDC5), has emerged as a promising therapeutic strategy to combat obesity and obesity-related complications. Various studies in mice have shown that irisin could respond to systematic exercise training and promote white-to-brown fat transdifferentiation, but the role and function of irisin in humans are controversial. In this review, we systematically introduced and analyzed the factors that may contribute to these inconsistent results. Furthermore, we also described the potential anti-inflammatory properties of irisin under a variety of inflammatory conditions. Finally, the review discussed the existing unresolved issues and controversies about irisin, including the transcription of the irisin precursor FNDC5 gene in humans, the cleavage site of the yet unknown proteolytic enzyme that cleaves irisin from FNDC5, and the reliability of irisin levels measured with available detection methods.

show abstract

“…Studies showed that FNDC5/Irisin is expressed in adipose tissue, cardiomyocytes, the brain and other parts of the body [ 12 , 13 ]. Recently the interest in the molecular actions of Irisin revealed that it is not only involved in energy storage and sensing, but it has a variety of molecular functions including differentiation, inflammation, oxidative stress in different systems [ 14 , 15 , 16 , 17 , 18 ]. The inhibitory effects of Irisin on cell apoptosis was shown to occur by modulation of pro-apoptotic markers such as the BCL2 associated agonist of death (BAD), BCL2 associated X apoptosis regulator (BAX), Caspase-9 and Caspase-3 and anti-apoptotic proteins such as BCL-2 and BCL-XL [ 16 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Irisin Protects the Human Placenta from Oxidative Stress and Apoptosis via Activation of the Akt Signaling Pathway

Kohan-Ghadr¹,

Armistead²,

Berg³

et al. 2021

IJMS

View full text Add to dashboard Cite

Irisin is a newly discovered exercise-mediated polypeptide hormone. Irisin levels increase during pregnancy however, women with preeclampsia (PE) have significantly lower levels of Irisin compared to women of healthy pregnancies. Even though many studies suggest a role of Irisin in pregnancy, its function in the human placenta is unclear. In the current study, we aimed to understand key roles of Irisin through its ability to protect against apoptosis is the preeclamptic placenta and in ex vivo and in vitro models of hypoxia/re-oxygenation (H/R) injury. Our studies show that Irisin prevents cell death by reducing pro-apoptotic signaling cascades, reducing cleavage of PARP to induce DNA repair pathways and reducing activity of Caspase 3. Irisin caused an increase in the levels of anti-apoptotic BCL2 to pro-apoptotic BAX and reduced ROS levels in an in vitro model of placental ischemia. Furthermore, we show that Irisin treatment acts through the Akt signaling pathway to prevent apoptosis and enhance cell survival. Our findings provide a novel understanding for the anti-apoptotic and pro-survival properties of Irisin in the human placenta under pathological conditions. This work yields new insights into placental development and disease and points towards intervention strategies for placental insufficiencies, such as PE, by protecting and maintaining placental function through inhibiting hypoxic ischemia-induced apoptosis.

show abstract

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

Cited by 70 publications

References 60 publications

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity

Irisin Protects the Human Placenta from Oxidative Stress and Apoptosis via Activation of the Akt Signaling Pathway

Contact Info

Product

Resources

About