The Potential Role of Irisin in Vascular Function and Atherosclerosis: A Review

Byun, Kyeongho; Lee, Sewon

doi:10.3390/ijms21197184

Cited by 29 publications

(18 citation statements)

References 54 publications

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“…A pre-vious meta-analysis including 23 studies showed that compared with non-diabetic controls, circulating irisin concentrations were significantly lower in patients with T2DM [10], suggesting a potential protective role of irisin for glycemic metabolism. This is also consistent with the findings from experimental studies, which confirmed various benefits of irisin in patients with T2DM, such as anti-inflammation, improving insulin resistance, and possibly anti-atherosclerosis [11][12][13][14][15]. Besides, lower serum level of irisin has been observed in T2DM patients with macrovascular complications [16,17], while previous studies evaluating the association between serum irisin and DN showed inconsistent results [18][19][20][21][22][23][24][25][26][27][28][29][30].…”

Section: Introductionsupporting

confidence: 89%

Association Between Serum Irisin and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis

Wang

Liu

2021

Horm Metab Res

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Irisin, an emerging adipokine, has been involved in the pathogenesis of type 2 diabetes mellitus (T2DM). However, previous studies evaluating the association between irisin and diabetic nephropathy (DN) showed inconsistent results. We performed a meta-analysis to evaluate the above association. Matched case-control studies evaluating the difference of serum irisin between T2DM patients with and without DN were identified via systematic search of PubMed, Embase, Cochranes’ Library, China National Knowledge Infrastructure, and WanFang databases from inception to December 5, 2020. A random-effects model or a fixed-effects model was used to pool the results according to the heterogeneity. Overall, thirteen matched case-control studies including 1735 T2DM patients were included. Results of meta-analysis showed that compared to T2DM patients with normoalbuminuria, those with microalbuminuria [10 studies, standard mean difference (SMD): 1.12, 95% confidence interval (CI): 0.48–1.77, p<0.001; I2=94%] and macroalbuminuria (10 studies, SMD: 1.86, 95% CI: 0.93–2.79, p<0.001; I2=97%) had significantly lower serum irisin. Besides, the serum level of irisin was significantly lower in T2DM patients with macroalbuminuria than those with microalbuminuria (10 studies, SMD: 0.91, 95% CI: 0.44–1.38, p<0.001; I2=90%). In addition, patients with estimated glomerular infiltration rate (eGFR)<60 ml/min 1.73 m2 had lower serum irisin compared to those with eGFR≥60 ml/min 1.73 m2 (4 studies, SMD: 0.89, 95% CI: 0.32–1.46, p=0.002; I2=91%). In conclusion, serum irisin may be associated with albuminuria and reduced eGFR in T2DM patients.

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Section: Introductionsupporting

confidence: 89%

Association Between Serum Irisin and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis

Wang

Liu

2021

Horm Metab Res

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“…PGC-1α and FNDC5 expression and increment in circulating level of irisin are known to enhance energy consumption and stimulate the browning of white adipose tissue (WAT), thereby ameliorating insulin resistance [ 3 ]. In addition, recent studies have reported that irisin had a protective effect on the dysfunction of pancreatic β cell [ 4 , 5 ] and vascular dysfunction [ 6 ]. In this regard, irisin is attracting attention as a signaling mechanism that can be used to treat metabolic diseases such as obesity, insulin resistance, and metabolic syndrome because it increases the expression of uncoupling protein 1 (UCP1) present in the inner membrane of mitochondria, thereby inducing the browning of WAT.…”

Section: Introductionmentioning

confidence: 99%

The Acute Effects of Swimming Exercise on PGC-1α-FNDC5/Irisin-UCP1 Expression in Male C57BL/6J Mice

et al. 2021

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Irisin is a myokine primarily secreted by skeletal muscles and is known as an exercise-induced hormone. The purpose of this study was to determine whether the PGC-1α -FNDC5 /Irisin-UCP1 expression which is an irisin-related signaling pathway, is activated by an acute swimming exercise. Fourteen to sixteen weeks old male C57BL/6J mice (n = 20) were divided into control (CON, n = 10) and swimming exercise groups (SEG, n = 10). The SEG mice performed 90 min of acute swimming exercise, while control (non-exercised) mice were exposed to shallow water (2 cm of depth) for 90 min. The mRNA and protein expression of PGC-1α, FNDC5 and browning markers including UCP1 were evaluated by quantitative real-time PCR and western blotting. Serum irisin concentration was measured by enzyme-linked immunosorbent assay. An acute swimming exercise did not lead to alterations in the mRNA and protein expression of PGC-1α in both soleus and gastrocnemius muscles, the mRNA and protein expression of UCP1 in brown adipose tissue, mRNA browning markers in visceral adipose tissue and circulating irisin when compared with the control group. On the other hand, an acute swimming exercise led to increases in the mRNA and protein expressions of FNDC5 in the soleus muscle, the protein expression of FNDC5 in the gastrocnemius muscles and the protein expression of UCP1 in subcutaneous adipose tissue.

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“…Accordingly, FNDC5/Irisin is considered as a direct transcriptional target of FXR, and may be a novel therapeutic strategy for dyslipidemia and atherosclerosis. Several studies have mentioned that irisin inhibits neointima formation, endothelial injury and inflammation in Apoe-/-mice model (12), Irisin reduced oxidized low density lipoprotein (oxLDL)-mediated endothelial cell apoptosis, inflammatory cytokines and intracellular ROS levels, and up-regulated p-AKT/ mechanistic target of rapamycin (mTOR)/NF-E2related factor 2 (Nrf2). In addition, mTOR/Nrf2 shRNA and LY294002 both ameliorate the protective effect of irisin, suggesting that irisin alleviates oxLDL-induced vascular injury through activation of Akt/mTOR/Nrf2 pathway (13).…”

Section: Introductionmentioning

confidence: 99%

Irisin ameliorates nicotine-mediated atherosclerosis via inhibition of the PI3K pathway

Li¹,

Chen²,

Wang³

et al. 2021

Ann Transl Med

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Background: Atherosclerosis is a chronic disease, with smoking being an independent risk factor. Irisin, a factor produced by myocytes, is expected to treat smoking-related arteriosclerosis, however its specific mechanism remains unclear.Methods: Forty Apoe-/-mice with nicotine intervention were involved in this study. The atherosclerotic lesions, smooth muscle cell proliferation, and macrophage infiltration induced by nicotine, and the corresponding changes caused by the administration of irisin, were obtained. The integrin αVβ5 inhibitor, cilengitide, was included to determine the cell entry pathway of irisin. Proteins and mRNA levels of phosphatidylinositol 3-kinase (PI3K) and downstreams were detected to clarify the specific molecular mechanism of irisin activity.Results: H&E staining and Masson staining showed that nicotine could aggravate the intensity of atherosclerosis in mice, and Irisin could reverse the thickening of the vascular media induced by nicotine.Immunohistochemical staining of CD68 and α-SMA suggested that Irisin could inhibit nicotine-mediated macrophage infiltration and smooth muscle cell proliferation. The protective effect of Irisin was partially reduced after the administration of cilengitide, confirming that Irisin enters cells through multiple ways, including integrin αvβ5. Nicotine was confirmed to activate the PI3K pathway to promote media thickening, while Irisin can inhibit the activation of the PI3K pathway, thus playing its anti-atherosclerosis role. Irisin was further observed to reverse nicotine-mediated P27 down-regulation.Conclusions: Irisin was found to inhibit nicotine-mediated medium thickening, smooth muscle cell proliferation, macrophage infiltration, and atherosclerosis progression via the integrin αVβ5/PI3K/P27 pathway.

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The Potential Role of Irisin in Vascular Function and Atherosclerosis: A Review

Cited by 29 publications

References 54 publications

Association Between Serum Irisin and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis

Association Between Serum Irisin and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis

The Acute Effects of Swimming Exercise on PGC-1α-FNDC5/Irisin-UCP1 Expression in Male C57BL/6J Mice

Irisin ameliorates nicotine-mediated atherosclerosis via inhibition of the PI3K pathway

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