The Role of FNDC5/Irisin in Cardiovascular Disease

Grzeszczuk, Maciej; Dzięgiel, Piotr; Nowińska, Katarzyna

doi:10.3390/cells13030277

Cited by 8 publications

(1 citation statement)

References 115 publications

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“…It is mainly synthesized during the muscle movement and secreted into the bloodstream. In endocrine function, it acts on the target organs or cells, thereby affecting their biological function, such as the conversion of white adipose tissue (WAT) to brown adipose tissue (BAT), and regulating oral hard and soft tissues and vascular calcification ( Pedersen and Febbraio, 2012 ; Saleem and Ghafoor, 2023 ; Grzeszczuk et al, 2024 ; Wang et al, 2024 ). Recently, irisin was found to enhance the intestinal barrier in NOD mice, postponing the onset of type 1 diabetes ( Sun et al, 2024 ).…”

Section: Discussionmentioning

confidence: 99%

Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics

Yang,

Deng,

Zhou

et al. 2024

Front. Microbiol.

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IntroductionFolliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity.MethodsMice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400μg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC–MS).ResultsIn this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4).ConclusionThese results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.

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Section: Discussionmentioning

confidence: 99%

Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics

Yang,

Deng,

Zhou

et al. 2024

Front. Microbiol.

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Hydrogen Sulfide and Irisin, Potential Allies in Ensuring Cardiovascular Health

Flori,

Benedetti,

Calderone

et al. 2024

Antioxidants

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Irisin is a myokine secreted under the influence of physical activity and exposure to low temperatures and through different exogenous stimuli by the cleavage of its precursor, fibronectin type III domain-containing protein 5 (FNDC5). It is mainly known for maintaining of metabolic homeostasis, promoting the browning of white adipose tissue, the thermogenesis process, and glucose homeostasis. Growing experimental evidence suggests the possible central role of irisin in the regulation of cardiometabolic pathophysiological processes. On the other side, hydrogen sulfide (H2S) is well recognized as a pleiotropic gasotransmitter that regulates several homeostatic balances and physiological functions and takes part in the pathogenesis of cardiometabolic diseases. Through the S-persulfidation of cysteine protein residues, H2S is capable of interacting with crucial signaling pathways, exerting beneficial effects in regulating glucose and lipid homeostasis as well. H2S and irisin seem to be intertwined; indeed, recently, H2S was found to regulate irisin secretion by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/FNDC5/irisin signaling pathway, and they share several mechanisms of action. Their involvement in metabolic diseases is confirmed by the detection of their lower circulating levels in obese and diabetic subjects. Along with the importance of metabolic disorders, these modulators exert favorable effects against cardiovascular diseases, preventing incidents of hypertension, atherosclerosis, heart failure, myocardial infarction, and ischemia–reperfusion injury. This review, for the first time, aims to explore the role of H2S and irisin and their possible crosstalk in cardiovascular diseases, pointing out the main effects exerted through the common molecular pathways involved.

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Irisin Predicts Poor Clinical Outcomes in Patients with Heart Failure with Preserved Ejection Fraction and Low Levels of N-Terminal Pro-B-Type Natriuretic Peptide

Berezina,

Berezin,

Novikov

et al. 2024

Biomolecules

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Background: Despite existing evidence of the high predictive value of natriuretic peptides (NPs) in patients with heart failure (HF), patients treated with guideline-directed therapy who have low or near-normal NP levels are unlikely to be correctly stratified for risk of clinical outcomes. The aim of this study is to detect plausible predictors for poor one-year clinical outcomes in patients with HFpEF and low NT-proBNP treated with in accordance with conventional guidelines. Methods: A total of 337 patients with HF with preserved ejection fraction (HFpEF) who had low levels of N-terminal natriuretic pro-peptide (NT-proBNP) at discharge due to optimal guideline-based therapy were enrolled in the study. The course of the observation was 3 years. Echocardiography and the assessment of conventional hematological and biochemical parameters, including NT-proBNP, tumor necrosis factor-alpha, high-sensitivity C-reactive protein (hs-CRP), adropin, irisin, visfatin, and fetuin-A, were performed at baseline and at the end of the study. Results: Three-year cumulative clinical endpoints (cardiovascular death, myocardial infarction or unstable angina or acute coronary syndrome, worsening HF, sudden cardiac death, or cardiac-related surgery or all-cause death) were detected in 104 patients, whereas 233 did not meet the endpoint. After adjusting for an age ≥ 64 years and a presence of atrial fibrillation, diabetes mellitus, chronic kidney disease (CKD) stages 1–3 and dilated cardiomyopathy, the multivariable Cox regression analysis showed that an irisin level of ≤7.2 ng/mL was an independent predictor of cumulative clinical endpoint. Moreover, patients with levels of irisin > 7.2 ng/mL had a better Kaplan–Meier survival rate than those with a lower serum irisin level (≤7.2 ng/mL). Conclusions: Multivariable analysis showed that an age ≥ 64 years; the presence of atrial fibrillation, diabetes mellitus, CKD stages 1–3 and dilated cardiomyopathy; an LAVI ≥ 39 mL/m2; and serum levels of hs-CRP ≥ 6.10 mg/L, irisin ≤ 7.2 ng/mL, and visfatin ≤ 1.1 ng/mL were predictors of poor clinical outcomes in HFpEF with low levels of NT-proBNP. A serum level of irisin ≤ 7.2 ng/mL could emerge as valuable biomarker for predicting long-term prognosis among HFpEF patients with low or near-normal levels of NT-proBNP.

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The Role of FNDC5/Irisin in Cardiovascular Disease

Cited by 8 publications

References 115 publications

Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics

Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics

Hydrogen Sulfide and Irisin, Potential Allies in Ensuring Cardiovascular Health

Irisin Predicts Poor Clinical Outcomes in Patients with Heart Failure with Preserved Ejection Fraction and Low Levels of N-Terminal Pro-B-Type Natriuretic Peptide

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