A role for FNDC5/Irisin in the beneficial effects of exercise on the brain and in neurodegenerative diseases

Young, Michael; Valaris, Sophia; Wrann, Christiane D.

doi:10.1016/j.pcad.2019.02.007

Cited by 104 publications

(75 citation statements)

References 73 publications

(91 reference statements)

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“…FNDC5 was recognized as a transmembrane protein with a bronectin III domain and a carboxy-terminal domain located in the cytoplasm (35) . Irisin is the extracellular domain of FNDC5, which is cleaved by enzyme (14,36) .…”

Section: Discussionmentioning

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

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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.

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Section: Discussionmentioning

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

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“…For all these reasons, irisin is considered a critical myokine related to body metabolism. Moreover, increasing evidence proposes irisin also as a mediator of the beneficial effects of exercise on the brain function (memory) and in neurodegenerative diseases …”

Section: Introductionmentioning

confidence: 99%

“…Moreover, increasing evidence proposes irisin also as a mediator of the beneficial effects of exercise on the brain function (memory) and in neurodegenerative diseases. [13][14][15] Although it was demonstrated that irisin expression is detectable around the paraventricular nucleus region in human hypothalamic sections where it colocalizes with NPY, 16 the potential role of irisin in the regulation of body weight and food intake is still unclear. Indeed, irisin administration has been shown to promote weight loss in diabetic mice or rats, [17][18][19][20][21][22] but other studies showed no differences in body weight between diabetic mice receiving irisin or not.…”

mentioning

confidence: 99%

Irisin increases the expression of anorexigenic and neurotrophic genes in mouse brain

Natalicchio

Marrano

Biondi

et al. 2019

Diabetes Metabolism Res

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Background Irisin, a newly discovered muscle‐derived hormone, acts in different organs and tissues, improving energy homeostasis. In this study, we assessed, for the first time, the effects of intraperitoneal irisin injections on circulating levels of leptin and ghrelin, mRNA expression of the major hypothalamic appetite regulators and brain neurotrophic factors, as well as feeding behaviour in healthy mice. Methods Twelve male 6‐week‐old C57BL/6 mice were randomized into two groups and intraperitoneally injected daily with irisin (0.5 μg/g body weight) or vehicle (phosphate‐buffered saline [PBS]) for 14 days. On the last day of observation, leptin and ghrelin levels were measured with an enzyme‐linked immunosorbent assay (ELISA). mRNA levels of genes of interest were analysed by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) in brain extracts. Results Irisin administration did not change leptin or ghrelin serum concentrations. However, irisin injection increased CART, POMC, NPY, and BDNF mRNA levels, without affecting the mRNA expression of AgRP, orexin, PMCH, and UCP2. Finally, over the time frame of irisin treatment, body weight and feeding behaviour were unaltered. Conclusions These results suggest that intraperitoneal injection of irisin, although without effects on feeding behaviour and body weight, can increase the expression of anorexigenic and neurotrophic genes in mouse brain.

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“…FNDC5 was recognized as a transmembrane protein with a fibronectin III domain and a carboxyterminal domain located in the cytoplasm (27) . Once FNDC5 could be cleaved by an unknown enzyme, and the extracellular domain of FNDC5 was named as irisin (12,28) .…”

Section: Discussionmentioning

confidence: 99%

FDNC5/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 FNDC5 +/+ in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5 +/+ . Results Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5 +/+ alleviated these injuries. Longitudinal in vivo bioluminescence imaging illustrated that MSCs FNDC5+/+ treatment improved the survival of transplanted MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo . Furthermore, MSCs FNDC5+/+ 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.

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A role for FNDC5/Irisin in the beneficial effects of exercise on the brain and in neurodegenerative diseases

Cited by 104 publications

References 73 publications

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

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

Irisin increases the expression of anorexigenic and neurotrophic genes in mouse brain

FDNC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

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