Irisin alleviates pressure overload-induced cardiac hypertrophy by inducing protective autophagy via mTOR-independent activation of the AMPK-ULK1 pathway

Li, Ruli; Wu, Sisi; Wu, Yao; Wang, Xiaoxiao; Chen, Hongying; Xin, Juan-Juan; Li, He; Lan, Jie; Xue, Kunyue; Li, Xue; Zhuo, Caili; Cai, Yuyan; He, Jinhan; Zhang, Heng-Yu; Tang, Chaoshu; Wang, Wang; Jiang, Wei

doi:10.1016/j.yjmcc.2018.07.250

Cited by 123 publications

(112 citation statements)

References 44 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…Since AMPK could also directly phosphorylate ULK1(unc‐51‐like kinase 1) to initiate autophagy, whereas mTOR negatively regulates ULK1 by phosphorylation of Ser757 to inhibit autophagy (Gui et al, ; Li et al, ). Thus, we explored whether AMPK directly activated autophagy independent of the inhibition of mTOR.…”

Section: Resultsmentioning

confidence: 99%

Alogliptin improves survival and health of mice on a high‐fat diet

Zhu

Xiang³

et al. 2019

Aging Cell

View full text Add to dashboard Cite

Alogliptin is a commonly prescribed drug treating patients with type 2 diabetes. Here, we show that long‐term intervention with alogliptin (0.03% w/w in diet) improves survival and health of mice on a high‐fat diet. Alogliptin intervention takes beneficial effects associated with longevity, including increased insulin sensitivity, attenuated functionality decline, decreased organ pathology, preserved mitochondrial function, and reduced oxidative stress. Autophagy activation is proposed as an underlying mechanism of these beneficial effects. We conclude that alogliptin intervention could be considered as a potential strategy for extending lifespan and healthspan in obesity and overweight.

show abstract

Section: Resultsmentioning

confidence: 99%

Alogliptin improves survival and health of mice on a high‐fat diet

Zhu

Xiang³

et al. 2019

Aging Cell

View full text Add to dashboard Cite

show abstract

“…Irisin is the extracellular domain of FNDC5, which is cleaved by enzyme (14,36) . Meanwhile, irisin has been proved as a multifunctional peptide that could bind to an unidenti ed receptor to play various effects (17,18) . Fatouros et al (15) found that irisin was secreted by skeletal muscles.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Irisin was recognized as a myokine secreted from skeletal muscle and heart (15 16) . Furthermore, irisin has been considered as a multifunctional peptide which is involved in regulating cardiovascular function (13,17,18) . Meanwhile, accumulating studies demonstrated that irisin was involved in cardioprotective effect, such as anti-apoptosis, increased cells viability and anti-oxidative stress by various pathways (19)(20) .…”

Section: Introductionmentioning

confidence: 99%

FNDC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

Deng

Zhang

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods: BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc+– eGFP+) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and overexpression of FNDC5 (FNDC5-OV) in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV. Results: Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging and immunofluorescence results illustrated that BM-MSCs with overexpression of FNDC5 treatment (FNDC5-MSCs) improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Interestingly, FNDC5-OV elevated the secretion of exosomes in BM-MSCs. Furthermore, FNDC5-MSCs therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions: The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.

show abstract

“…ULK1 plays an essential role in the initiation of autophagy and can be regulated by AMPK and mTOR via direct phosphorylation at Ser555 and Ser757, respectively. Irisin increased the activity of AMPK but not Akt and MAPK in hypertrophic hearts and cultured cardiomyocytes which triggered further activation of ULK1 at Ser555 but not Ser757 and did not affect the mTOR-S6K axis [82]. Irisin may also display anti-fibrotic therapeutic potential to counter angiotensin II-related cardiac fibrosis.…”

Section: Irisin Improves Cardiac Hypertrophy By Inducing Protective Amentioning

confidence: 97%

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways

et al. 2020

View full text Add to dashboard Cite

Fndc5, a well-defined myokine and also identified as an adipokine, has a critical role in modulation of metabolism and protection against obesity. These important functions are mediated by irisin, a secretory peptide produced from proteolytic processing of Fndc5. The other beneficial physiological effects of irisin are alleviation of oxidative stress, neuroprotective effects, and anti-inflammatory properties and associated anti-metastatic effects. Fndc5/irisin exerts its biological effects through several intracellular signaling pathways. The major signaling pathway is thought to be MAPK signaling pathways which are involved in neural differentiation, browning of white adipocytes, as well as osteoblast proliferation and differentiation. Other essential functions of Fndc5/irisin are mediated through additional pathways including AMPK pathway, PI3K/AKT, and STAT3/Snail. Thorough understanding of the mechanisms of irisin actions are essential in order to develop Fndc5/irisin for therapeutic purposes. In the present review, we focus on the current knowledge of the signaling pathways that elicit irisin actions.

show abstract

Irisin alleviates pressure overload-induced cardiac hypertrophy by inducing protective autophagy via mTOR-independent activation of the AMPK-ULK1 pathway

Cited by 123 publications

References 44 publications

Alogliptin improves survival and health of mice on a high‐fat diet

Alogliptin improves survival and health of mice on a high‐fat diet

FNDC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways

Contact Info

Product

Resources

About