Meteorin-like protein (METRNL)/IL-41 improves LPS-induced inflammatory responses via AMPK or PPARδ–mediated signaling pathways

Jung, Tae Woo; Pyun, Do Hyeon; Kim, Tae Jin; Lee, Hyun Jung; Park, Eon Sub; El‐Aty, A.M. Abd; Hwang, Eui Jin; Shin, Yong Kyoo; Jeong, Ji Hoon

doi:10.1016/j.advms.2021.01.007

Cited by 29 publications

(19 citation statements)

References 32 publications

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“…Activation of AMPK triggers the downstream signaling pathways by inducing the targeted proteins FOXO3a or G-alpha-interacting vesicle-associated protein (GIV) phosphorylation leading to autophagy induction ( 7 ) and tumor suppression ( 8 ). Furthermore, the interaction of AMPK with peroxisome proliferator–activated receptor δ (PPARδ) regulates glucose metabolism, vascular–endothelial dysfunction, insulin resistance, and inflammation ( 9 , 10 , 11 , 12 ). AMPK interacts with PPARδ leading to increased endurance or training adaptation in mice ( 9 ).…”

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confidence: 99%

“…Omentin-1 inhibits vascular–endothelial dysfunction in response to high glucose, which is associated with inhibition of the AMPK/PPARδ signaling pathway ( 10 ). METRNL alleviates insulin resistance and inflammation in response to lipid or LPS ( 11 , 12 ), which is involved in activation of AMPK and PPARδ pathways. In addition, PPARδ agonist GW501516-induced glucose uptake of human skeletal muscle cells is AMPK dependent rather than PPARδ ( 13 ).…”

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confidence: 99%

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AMPK phosphorylates PPARδ to mediate its stabilization, inhibit glucose and glutamine uptake and colon tumor growth

Ding

Gou

Jia

et al. 2021

Journal of Biological Chemistry

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confidence: 99%

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confidence: 99%

AMPK phosphorylates PPARδ to mediate its stabilization, inhibit glucose and glutamine uptake and colon tumor growth

Ding

Gou

Jia

et al. 2021

Journal of Biological Chemistry

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“…The positive correlation of elevated METRNb levels with disease severity parameters such as D-dimer (32), CRP, LDH (33) and ALP (34), and that elevated METRNb levels in parallel with the longitudinal elevation of multiple cytokines/chemokines for the pathogenic cytokine storm of COVID-19, show that METRNb is a valuable prognostic marker of COVID-19. As METRNb is considered a cytokine (31,35,36), therefore, these findings also suggest that METRNb contributes to the modulation of the cytokine storm in COVID-19.…”

Section: Discussionmentioning

confidence: 75%

Characterization of METRNβ as a novel biomarker of Coronavirus disease 2019 severity and prognosis

Gao

Chan²,

Wong³

et al. 2023

Front. Immunol.

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IntroductionCoronavirus disease 2019 (COVID-19) is increasing worldwide, with complications due to frequent viral mutations, an intricate pathophysiology, and variable host immune responses. Biomarkers with predictive and prognostic value are crucial but lacking.MethodsSerum samples from authentic and D614G variant (non-Omicron), and Omicron-SARS-CoV-2 infected patients were collected for METRNβ detection and longitudinal cytokine/chemokine analysis. Correlation analyses were performed to compare the relationships between serum METRNβ levels and cytokines/chemokines, laboratory parameters, and disease severity. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were used to evaluate the predictive value of METRNβ in COVID-19.ResultsThe serum level of METRNβ was highly elevated in non-Omicron-SARS-CoV-2 infected patients compared to healthy individuals, and the non-survivor displayed higher METRNβ levels than survivors among the critical ones. METRNβ concentration showed positive correlation with viral load in NAPS. ROC curve showed that a baseline METRNβ level of 1886.89 pg/ml distinguished COVID-19 patients from non-infected individuals with an AUC of 0.830. Longitudinal analysis of cytokine/chemokine profiles revealed a positive correlation between METRNβ and pro-inflammatory cytokines such as IL6, and an inverse correlation with soluble CD40L (sCD40L). Higher METRNβ was associated with increased mortality. These findings were validated in a second and third cohort of COVID-19 patients identified in a subsequent wave.DiscussionOur study uncovered the precise role of METRNβ in predicting the severity of COVID-19, thus providing a scientific basis for further evaluation of the role of METRNβ in triage therapeutic strategies.

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“…Consistent with our findings, METRNL knockout mice reportedly displayed dysregulated cytokine production and were highly susceptible to LPS in a sepsis model [ 52 ]. Moreover, recombinant METRNL treatment was found to alleviate inflammation in skeletal muscle and endothelial cells via AMPK or PPARδ signaling [ 23 , 53 ]. In addition, METRNL suppressed gene expression of NLRP3 inflammasome components in adipocytes, although no changes were observed at the protein level.…”

Section: Discussionmentioning

confidence: 99%

Exercise Inhibits NLRP3 Inflammasome Activation in Obese Mice via the Anti-Inflammatory Effect of Meteorin-like

Javaid

Sahar

ZhuGe

et al. 2021

Cells

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Obesity is associated with chronic low-grade inflammation. The benefits of exercise are partly attributed to its anti-inflammatory effect, but whether exercise can regulate NLRP3 inflammasome activation in obese adipose tissue remains unknown. Meteorin-like (METRNL), a recently discovered myokine, has been implicated in mediating the effect of exercise on metabolism. Herein, we examined the effect of exercise and METRNL on NLRP3 inflammasome activation. High-fat diet (HFD)-induced obese mice were subjected to treadmill exercise for 8 weeks. A subgroup of HFD mice was switched to normal chow with the exercise intervention. Exercise and diet attenuated weight gain, fat accumulation, and insulin resistance in obese mice. In addition, exercise downregulated gene and protein levels of inflammasome markers, including NLRP3 and caspase-1, in adipose tissue. In isolated bone marrow-derived macrophages, activation of NLRP3 inflammasome was suppressed in the exercise group, as confirmed by the downregulation of IL-1β and IL-18. Exercise significantly enhanced the expression of METRNL in various muscle depots, and further in vitro analysis revealed that recombinant METRNL treatment inhibited IL-1β secretion in macrophages. In conclusion, exercise exerts its anti-inflammatory action by suppressing adipose tissue NLRP3 inflammasome, and this is, in part, associated with METRNL induction in muscle and its anti-inflammatory effects in macrophages.

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Meteorin-like protein (METRNL)/IL-41 improves LPS-induced inflammatory responses via AMPK or PPARδ–mediated signaling pathways

Cited by 29 publications

References 32 publications

AMPK phosphorylates PPARδ to mediate its stabilization, inhibit glucose and glutamine uptake and colon tumor growth

AMPK phosphorylates PPARδ to mediate its stabilization, inhibit glucose and glutamine uptake and colon tumor growth

Characterization of METRNβ as a novel biomarker of Coronavirus disease 2019 severity and prognosis

Exercise Inhibits NLRP3 Inflammasome Activation in Obese Mice via the Anti-Inflammatory Effect of Meteorin-like

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