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Search Results (267)

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12 pages, 569 KiB  
Review
The Role of Myokines in Liver Diseases
by Hiroki Nishikawa, Soo Ki Kim and Akira Asai
Int. J. Mol. Sci. 2025, 26(3), 1043; https://doi.org/10.3390/ijms26031043 (registering DOI) - 25 Jan 2025
Viewed by 252
Abstract
Myokine is a general term for hormones, peptides, and other substances secreted by skeletal muscle. Myokine has attracted much attention in recent years as a key substance for understanding the mechanism of “exercise and health”. Skeletal muscle accounts for about 40% of the [...] Read more.
Myokine is a general term for hormones, peptides, and other substances secreted by skeletal muscle. Myokine has attracted much attention in recent years as a key substance for understanding the mechanism of “exercise and health”. Skeletal muscle accounts for about 40% of the total human weight and is now recognized as an endocrine organ that produces myokines, which have physiological activity. Representative myokines include IL-6, myostatin, irisin, brain-derived neurotropic factor, fibroblast growth factor-21, and decorin. On the other hand, sarcopenia, defined by quantitative and qualitative loss of skeletal muscle, is a condition that has received much attention in recent years because of its close correlation with prognosis. In patients with chronic liver disease (CLD), sarcopenia is a common complication. Mechanisms underlying sarcopenia in CLD patients have been reported to involve protein-energy malnutrition, which is characteristic of patients with cirrhosis, signaling involved in protein synthesis and degradation, myokines such as myostatin and decorin, the ubiquitin-proteasome pathway, sex hormones such as testosterone, dysbiosis, and insulin resistance, etc., in addition to aging. Each of these pathological conditions is thought to be intricately related to each other, leading to sarcopenia. This review will summarize the relationship between CLD and myokines. Full article
10 pages, 564 KiB  
Article
Influence of Sex and Age on Irisin Levels in Pediatric Type 1 Diabetes: A Pilot Study
by Shay Averbuch, Oxana Gaiduk, Michal Yackobovitch-Gavan, Irina Laurian, Anna Dorfman, Gabi Shefer, Avivit Brener and Yael Lebenthal
J. Clin. Med. 2025, 14(3), 793; https://doi.org/10.3390/jcm14030793 (registering DOI) - 25 Jan 2025
Viewed by 325
Abstract
Background: Irisin is a myokine involved in the browning of adipocytes, the regulation of body composition and the enhancement of glycemic control. Additionally, irisin has been suggested to play a role in signaling mechanisms associated with the onset of puberty. In this [...] Read more.
Background: Irisin is a myokine involved in the browning of adipocytes, the regulation of body composition and the enhancement of glycemic control. Additionally, irisin has been suggested to play a role in signaling mechanisms associated with the onset of puberty. In this study, we aimed to explore the interaction between muscle and adipose indices, urine irisin levels and glycemic control. Methods: This cross-sectional pilot study enrolled 76 consecutive pediatric patients (mean age 11.7 ± 3.8 years) diagnosed with type 1 diabetes (mean disease duration 2.1 ± 1.6 years). Body composition was assessed by bioelectrical impedance analysis (MFR z-score and skeletal muscle mass index). Urine irisin levels and glycemic control parameters (HbA1c, insulin dose-adjusted A1c [IDAA1c]) were evaluated. One linear regression model, stratified by sex, analyzed the sex-specific impact of puberty and age on irisin levels. A second linear regression model explored the associations of selected variables with irisin levels. Results: The first linear regression model revealed that irisin levels rise with age in prepubertal boys and decline with increased age among pubertal boys. The second linear regression analysis revealed no significant associations between irisin levels and metabolic parameters after adjusting for covariates. In contrast to boys, there were no significant interactions found in girls. Conclusions: Our novel findings revealed sex and age differences in the irisin levels of children and adolescents with type 1 diabetes. The dynamics underlying the role of irisin during pubertal development in the pediatric population with diabetes warrant further exploration. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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<p>A graphical depiction of a linear regression model illustrating that irisin levels increase with age among prepubertal boys and decrease with age among pubertal boys.</p>
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19 pages, 1629 KiB  
Article
The Effect of the Glucosinolate Sinigrin on Alterations in Molecular Biomarkers of the Myocardium in Swiss Mice
by Nikola Ferara, Vedran Balta, Domagoj Đikić, Dyana Odeh, Ana Mojsović-Ćuić, Lana Feher Turković, Dario Dilber, Anđelo Beletić, Irena Landeka Jurčević and Ivana Šola
Foods 2025, 14(2), 327; https://doi.org/10.3390/foods14020327 - 20 Jan 2025
Viewed by 620
Abstract
Glucosinolates are chemically stable compounds that exhibit biological activity in the body following hydrolysis catalyzed by the enzyme myrosinase. While existing in vitro and in vivo studies suggest that the hydrolysis products of glucosinolates predominantly exert beneficial effects in both human and animal [...] Read more.
Glucosinolates are chemically stable compounds that exhibit biological activity in the body following hydrolysis catalyzed by the enzyme myrosinase. While existing in vitro and in vivo studies suggest that the hydrolysis products of glucosinolates predominantly exert beneficial effects in both human and animal organisms, some studies have found that the excessive consumption of glucosinolates may lead to toxic and anti-nutritional effects. Given that glucosinolates are primarily ingested in the human diet through dietary supplements and commercially available cruciferous vegetables, we investigated the in vivo effects of the glucosinolate sinigrin on molecular markers in the myocardia of healthy Swiss mice. This study aims to elucidate whether sinigrin induces positive or negative physiological effects in mammals following consumption. The alterations in myocardial parameters were assessed by measuring metabolic, inflammatory, structural, and antioxidant markers. Our findings revealed that subchronic exposure to sinigrin in the myocardia of female mice resulted in a significant increase (p ≤ 0.05) in the levels of the myokine irisin, matrix metalloproteinases (MMP-2, MMP-9), catalase (CAT), and total glutathione (tGSH), alongside a marked decrease (p ≤ 0.05) in the levels of atrial natriuretic peptide (ANP), compared to the control group consisting of both female and male mice. These results suggest that the hydrolysis products of sinigrin may exert a potentially toxic effect on the myocardial tissue of female mice and possess the capability to modulate transcription factors in vivo in a sex-dependent manner. This observation calls for further investigation into the mechanisms regulating the actions of glucosinolate hydrolysis products, their interactions with sex hormones, and the determination of permissible intake levels associated with both beneficial and adverse outcomes. Full article
(This article belongs to the Section Plant Foods)
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<p>The effect of sinigrin on the concentrations of (<b>a</b>) adropin, (<b>b</b>) irisin, (<b>c</b>) atrial natriuretic peptide (ANP), and (<b>d</b>) peroxisomal acyl-CoA oxidase I (ACOX1) in cardiac tissue homogenates. Mice (N = 6) in both female and male control groups were treated intragastrically (<span class="html-italic">ig</span>) with 0.3 mL of physiological saline, while in the experimental groups, females and males were treated <span class="html-italic">ig</span> with 0.3 mL of an aqueous solution of sinigrin at a dose of 10 mg/kg once daily for 28 days. #: statistically significantly different from the Cont.F group (<span class="html-italic">p</span> ≤ 0.05); *: statistically significantly different from the Sinig.<sub>M</sub> group (<span class="html-italic">p</span> ≤ 0.05); **: statistically significantly different from the Cont.<sub>M</sub> group (<span class="html-italic">p</span> ≤ 0.05). The results are presented as the mean ± standard error. Abbreviations: Cont.<sub>M</sub>—male control group; Cont.<sub>F</sub>—female control group; Sinig.<sub>M</sub>—group of males treated with an aqueous solution of sinigrin; Sinig.<sub>F</sub>—group of females treated with an aqueous solution of sinigrin.</p>
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<p>The effect of sinigrin on the concentration of high-sensitivity cardiac troponin I (hs-cTnI) in cardiac tissue homogenates. Mice (N = 6) in both the female and male control groups were treated intragastrically (<span class="html-italic">ig</span>) with 0.3 mL of physiological saline, while in the experimental groups, females and males were treated <span class="html-italic">ig</span> with 0.3 mL of an aqueous solution of sinigrin at a dose of 10 mg/kg once daily for 28 days. The results are presented as the mean ± standard error. Abbreviations: Cont.<sub>M</sub>—male control group; Cont.<sub>F</sub>—female control group; Sinig.<sub>M</sub>—experimental group of males treated with an aqueous solution of sinigrin; Sinig.<sub>F</sub>—experimental group of females treated with an aqueous solution of sinigrin.</p>
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<p>The effect of sinigrin on the concentrations of (<b>a</b>) matrix metalloproteinase 2 (MMP-2), (<b>b</b>) matrix metalloproteinase 9 (MMP-9), (<b>c</b>) pentraxin 3 (PTX3), and (<b>d</b>) nitric oxide (NO) in cardiac tissue homogenates. Mice (N = 6) in both the female and male control groups were treated intragastrically (<span class="html-italic">ig</span>) with 0.3 mL of physiological saline, while in the experimental groups, females and males were treated <span class="html-italic">ig</span> with 0.3 mL of an aqueous solution of sinigrin at a dose of 10 mg/kg once daily for 28 days. #: statistically significantly different from the Cont.<sub>F</sub> group (<span class="html-italic">p</span> ≤ 0.05). The results are presented as the mean ± standard error. Abbreviations: Cont.<sub>M</sub>—male control group; Cont.<sub>F</sub>—female control group; Sinig.<sub>M</sub>—experimental group of males treated with an aqueous solution of sinigrin; Sinig.<sub>F</sub>—experimental group of females treated with an aqueous solution of sinigrin.</p>
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<p>The effect of sinigrin on (<b>a</b>) superoxide dismutase (SOD) activity, (<b>b</b>) catalase (CAT) activity, (<b>c</b>) malondialdehyde (MDA) concentration, and (<b>d</b>) total glutathione (tGSH) concentration in cardiac tissue homogenates. Mice (N = 6) in both the female and male control groups were treated intragastrically (<span class="html-italic">ig</span>) with 0.3 mL of physiological saline, while in the experimental groups, females and males were treated <span class="html-italic">ig</span> with 0.3 mL of an aqueous solution of sinigrin at a dose of 10 mg/kg once daily for 28 days. #: statistically significantly different from the Cont.F group (<span class="html-italic">p</span> ≤ 0.05); *: statistically significantly different from the Sinig.<sub>M</sub> group (<span class="html-italic">p</span> ≤ 0.05). The results are presented as the mean ± standard error. Abbreviations: Cont.<sub>M</sub>—male control group; Cont.<sub>F</sub>—female control group; Sinig.<sub>M</sub>—experimental group of males treated with an aqueous solution of sinigrin; Sinig.<sub>F</sub>—experimental group of females treated with an aqueous solution of sinigrin.</p>
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13 pages, 2365 KiB  
Article
Irisin and Metastatic Melanoma: Selective Anti-Invasiveness Activity in BRAF Wild-Type Cells
by Simona Serratì, Roberta Zerlotin, Michele Manganelli, Roberta Di Fonte, Manuela Dicarlo, Angela Oranger, Graziana Colaianni, Letizia Porcelli, Amalia Azzariti, Stefania Guida, Maria Grano, Silvia Concetta Colucci and Gabriella Guida
Int. J. Mol. Sci. 2025, 26(2), 652; https://doi.org/10.3390/ijms26020652 - 14 Jan 2025
Viewed by 361
Abstract
Irisin is a newly discovered 12 kDa messenger protein involved in energy metabolism. Irisin affects signaling pathways in several types of cancer; however, the role of irisin in metastatic melanoma (MM) has not been described yet. We explored the biological effects of irisin [...] Read more.
Irisin is a newly discovered 12 kDa messenger protein involved in energy metabolism. Irisin affects signaling pathways in several types of cancer; however, the role of irisin in metastatic melanoma (MM) has not been described yet. We explored the biological effects of irisin in in vitro models of MM cells (HBLwt/wt, LND1wt/wt, Hmel1V600K/wt and M3V600E/V600E) capable of the oncogenic activation of BRAF. We treated MM cells with different concentrations of r-irisin (10 nM, 25 nM, 50 nM, 100 nM) for 24 h–48 h. An MTT assay highlighted that r-irisin did not affect the proliferation of MM cells. We subsequently treated MM cells with 10 nM r-irisin, corresponding to the dose exhibiting biological activity in vitro. Irisin reduced the invasive ability of only LND1wt/wt (p < 0.05), which highly expressed αv gene levels, but did not affect the invasion of BRAFmut cells. Gelatin zymography analysis showed a reduction in the enzymatic activity of MMP-2 and MMP-9 in BRAFwt/wt cells treated with 10 nM r-irisin. Moreover, gene expression analysis (qPCR) of MMP-2 and MMP-9 and of the fibrinolytic system (uPAR, uPA and PAI-1) highlighted a crucial role of 10 nM r-irisin treatment in the inhibition of pro-invasive systems in BRAFwt/wt. In conclusion, our results may suggest a possible differential role of irisin in melanoma cells. Full article
(This article belongs to the Special Issue Skin Diseases: From Molecular Mechanisms to Pathology)
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<p>MTT-assay. Metastatic melanoma cell lines were treated with different concentrations of r-irisin (10 nM, 20 nM, 50 nM, 100 nM) for 24 h and 48 h (<b>A</b>–<b>D</b>). MTT assays were performed with at least three replicates per experimental condition. ns = not significant.</p>
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<p>Chemio-Invasion assay. Melanoma cells were migrated through Matrigel-coated porous filters in a 10 nM irisin gradient, showing a reduction in the invasion potential of (<b>A</b>) HBL<sup>wt/wt</sup> and LND1<sup>wt/wt</sup> compared to untreated (* <span class="html-italic">p</span> &lt; 0.05) and (<b>B</b>) BRAF<sup>mut</sup> cells Hmel1<sup>V600K/wt</sup> and M3<sup>V600E/V600E</sup>. The Chemio-Invasion assay was performed with at least three replicates per experimental condition. Scale bar: 200 μm. Magnification: 200×.</p>
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<p>qRT-PCR analysis of alpha-V integrin. Alpha-V gene expression in different MM cell lines. Experiments were performed in triplicates. The histograms represent the means while the error bars present ±SD. * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>qRT-PCR analysis. Gene expression of the urokinase plasminogen activator receptor (uPAR), urokinase plasminogen activator (uPA) and its inhibitor PAI-1 in the different MM cell lines. Experiments were performed in triplicates. Histograms represent means while error bars represent ±SD. Unpaired two-tailed <span class="html-italic">t</span>-test. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Western blot analysis. Representative immunoblots showing uPAR, uPA, and PAI-1 protein expression in the MM cell line treated with r-irisin 10 nM. Stain-free staining of total proteins loaded onto the gel was carried out for normalization by densitometric analyses, as described in <a href="#sec4-ijms-26-00652" class="html-sec">Section 4</a>.</p>
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<p><b>Analysis of gelatinase system.</b> (<b>A</b>) Gene expression pattern of the gelatinase system (MMP-9, MMP-2, TIMP-1 and TIMP-2) in the four different MM cell lines following r-irisin treatment. Experiments were performed in triplicates. Unpaired two-tailed <span class="html-italic">t</span>-test. <span class="html-italic">p</span> &lt; 0.01, **; <span class="html-italic">p</span> &lt; 0.001 ***. (<b>B</b>) Zymography assay for MMP-9 and MMP-2 in the four different MM cell lines following irisin treatment.</p>
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17 pages, 821 KiB  
Review
Understanding the Role of Irisin in Longevity and Aging: A Narrative Review
by Ana I. Plácido, Daniela Azevedo, Maria Teresa Herdeiro, Manuel Morgado and Fátima Roque
Epidemiologia 2025, 6(1), 1; https://doi.org/10.3390/epidemiologia6010001 - 8 Jan 2025
Viewed by 636
Abstract
Irisin is a protein resulting from a proteolytic cleavage of fibronectin type III domain-containing protein 5 (FND5). The ability of irisin to modulate adipocyte and control glucose metabolism in human metabolic diseases gave rise to the hypothesis that irisin could have a pivotal [...] Read more.
Irisin is a protein resulting from a proteolytic cleavage of fibronectin type III domain-containing protein 5 (FND5). The ability of irisin to modulate adipocyte and control glucose metabolism in human metabolic diseases gave rise to the hypothesis that irisin could have a pivotal role in aging-related diseases. Although in animal models, increased levels of irisin have been positively associated with better health outcomes, in humans, its role remains controversial. To provide an overview of the main finding on irisin in older adults, a comprehensive search was performed through the MEDLINE-PubMed, Web of Science, Scopus, and Cochrane databases for studies conducted in older adults (≥60 years) published since 2012. After grouping and analyzing the articles based on diseases associated with older adults, the main conclusion of this narrative review is that the included studies did not yield consistent evidence regarding the association between irisin and health or disease in older adults. Further studies are necessary to clarify the effective role of this protein in promoting health and longevity. Full article
(This article belongs to the Special Issue Global Health Epidemiology and Disease Control)
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<p>Flow diagram of the literature selection that occurred in this review.</p>
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<p>Irisin serum levels according to health condition and/or intervention in older adults.</p>
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20 pages, 699 KiB  
Article
Maximal Intensity Exercise Induces Adipokine Secretion and Disrupts Prooxidant–Antioxidant Balance in Young Men with Different Body Composition
by Magdalena Wiecek, Mateusz Mardyla, Jadwiga Szymura, Malgorzata Kantorowicz, Justyna Kusmierczyk, Marcin Maciejczyk and Zbigniew Szygula
Int. J. Mol. Sci. 2025, 26(1), 350; https://doi.org/10.3390/ijms26010350 - 3 Jan 2025
Viewed by 548
Abstract
Maximal physical effort induces a disturbance in the body’s energy homeostasis and causes oxidative stress. The aim of the study was to determine whether prooxidant–antioxidant balance disturbances and the secretion of adipokines regulating metabolism, induced by maximal intensity exercise, are dependent on body [...] Read more.
Maximal physical effort induces a disturbance in the body’s energy homeostasis and causes oxidative stress. The aim of the study was to determine whether prooxidant–antioxidant balance disturbances and the secretion of adipokines regulating metabolism, induced by maximal intensity exercise, are dependent on body composition in young, healthy, non-obese individuals. We determined changes in the concentration of advanced protein oxidation products (AOPP), markers of oxidative damage to nucleic acids (DNA/RNA/ox), and lipid peroxidation (LPO); catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity, as well as concentrations of visfatin, leptin, resistin, adiponectin, asprosin, and irisin in the blood before and after maximal intensity exercise in men with above-average muscle mass (NFAT-HLBM), above-average fat mass (HFAT-NLBM), and with average body composition (NFAT-NLBM). We corrected the post-exercise results for the percentage change in plasma volume. In all groups after exercise, there was an increase in LPO and resistin. In HFAT-NLBM, additionally, an increase in CAT and a decrease in SOD activity were noted, and in NFAT-NLBM, an increase in visfatin concentration was observed. In our study, the effect was demonstrated of a maximal effort on six (LPO, CAT, SOD, visfatin, resistin, and asprosin) of the twelve parameters investigated, while the effect of body composition on all parameters investigated was insignificant. Maximal intensity aerobic exercise induces secretion of resistin and damages lipids regardless of the exercising subjects’ body composition. Large fat tissue content predisposes to exercise-induced disorders in the activity of antioxidant enzymes. We have also shown that it is necessary to consider changes in blood plasma volume in the assessment of post-exercise biochemical marker levels. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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<p>Concentration of prooxidant–antioxidant balance markers before (T0), as well as after maximal intensity exercise, without correction (T1) and after correction for percentage plasma volume changes (T1<sub>PV</sub>): (<b>a</b>) AOPP—advanced protein oxidation products; (<b>b</b>) DNA/RNA/ox—markers of oxidative damage to nucleic acids; (<b>c</b>) LPO—markers of lipid peroxidation; (<b>d</b>) CAT—catalase; (<b>e</b>) SOD—superoxide dismutase; (<b>f</b>) GPx—glutathione peroxidase; <span class="html-italic">p</span> &lt; 0.05—statistically significant difference T1 vs. T0 and T1<sub>PV</sub> vs. T0 in each group (post hoc Tukey’s HSD test following two-way repeated measures analysis of variance for data (1) without correction for %dPV of post-exercise values and independently (2) with correction for %dPV of post-exercise values); NFAT-NLBM—group with average content of %FAT and with average content of LBM, NFAT-HLBM—group with average content of %FAT and above-average content of LBM, HFAT-NLBM—group with above-average content of %FAT and average content of LBM; marker—mean, box—standard error (SE), whisker—standard deviation (SD).</p>
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<p>Concentration of adipokines: visfatin (<b>a</b>), leptin (<b>b</b>), resistin (<b>c</b>), adiponectin (<b>d</b>), asprosin (<b>e</b>), and irisin (<b>f</b>), before (T0), as well as after maximal intensity exercise without (T1) and after correction for percentage plasma volume changes (T1<sub>PV</sub>); <span class="html-italic">p</span> &lt; 0.05—statistically significant difference T1 vs. T0 and T1<sub>PV</sub> vs. T0 in each group (post hoc Tukey’s HSD test following two-way repeated measures analysis of variance for data (1) without correction for %dPV of post-exercise values and independently, (2) with correction for %dPV of post-exercise values); NFAT-NLBM—group with an average content of %FAT and with an average content of LBM, NFAT-HLBM—group with an average content of %FAT and above-average content of LBM, HFAT-NLBM—group with above-average content of %FAT and average content of LBM; marker—mean, box—standard error (SE), whisker—standard deviation (SD).</p>
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22 pages, 2905 KiB  
Review
Physical Exercise: A Promising Treatment Against Organ Fibrosis
by Xiaojie Ma, Bing Liu, Ziming Jiang, Zhijian Rao and Lifang Zheng
Int. J. Mol. Sci. 2025, 26(1), 343; https://doi.org/10.3390/ijms26010343 - 2 Jan 2025
Viewed by 851
Abstract
Fibrosis represents a terminal pathological manifestation encountered in numerous chronic diseases. The process involves the persistent infiltration of inflammatory cells, the transdifferentiation of fibroblasts into myofibroblasts, and the excessive deposition of extracellular matrix (ECM) within damaged tissues, all of which are characteristic features [...] Read more.
Fibrosis represents a terminal pathological manifestation encountered in numerous chronic diseases. The process involves the persistent infiltration of inflammatory cells, the transdifferentiation of fibroblasts into myofibroblasts, and the excessive deposition of extracellular matrix (ECM) within damaged tissues, all of which are characteristic features of organ fibrosis. Extensive documentation exists on fibrosis occurrence in vital organs such as the liver, heart, lungs, kidneys, and skeletal muscles, elucidating its underlying pathological mechanisms. Regular exercise is known to confer health benefits through its anti-inflammatory, antioxidant, and anti-aging effects. Notably, exercise exerts anti-fibrotic effects by modulating multiple pathways, including transforming growth factor-β1/small mother decapentaplegic protein (TGF-β1/Samd), Wnt/β-catenin, nuclear factor kappa-B (NF-kB), reactive oxygen species (ROS), microRNAs (miR-126, miR-29a, miR-101a), and exerkine (FGF21, irisin, FSTL1, and CHI3L1). Therefore, this paper aims to review the specific role and molecular mechanisms of exercise as a potential intervention to ameliorate organ fibrosis. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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<p>The pathogenesis of fibrosis: After tissue injury, immune cells (mainly macrophages) are activated and release cytokines (e.g., IL-4, IL-13, PDGF, TGF-β, etc.). Through signaling pathways such as TGF-β/Smad and Wnt/β-catenin, fibroblasts are transformed into myofibroblasts, and myofibroblasts produce a large amount of ECM, leading to the generation of fibrosis. IL-4: interleukin-4; IL-13: interleukin-13; IL-1β: interleukin-1β; TGF-β: transforming growth factor-β; smad: small mother decapentaplegic protein; PDGF: platelet-derived growth factor-D; ERK: extracellular signal-regulated kinase; p38: p38 mitogen-activated protein kinases; JNK: c-Jun N-terminal kinases; TAK1: transforming growth factor-β (TGF-β)-activated kinase 1; α-SMA: α-smooth muscle actin; COL1: Collagen 1; COL3: Collagen 3; MMP: matrix metallopeptidase; TIMP-1: tissue inhibitor of metal protease1. Created with Figdraw (<a href="http://www.figdraw.com" target="_blank">www.figdraw.com</a>), license ID: TTWOW4366f.</p>
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<p>The mechanisms of exercise modulation of pulmonary fibrosis. Exercise ameliorates paraquat-induced pulmonary fibrosis by impeding the Wnt/β-catenin pathway, dampening inflammation, oxidative stress, and EMT. In bleomycin-induced pulmonary fibrosis, exercise alleviates fibrosis by enhancing endogenous hydrogen sulfide (H<sub>2</sub>S) synthesis, thereby inhibiting the LRP-6/β-catenin and TGF-β1 signaling pathways or reducing lung inflammation and EMT via the suppression of serotonin (5-HT) and Akt phosphorylation. Additionally, in silica-induced silicosis, exercise attenuates lung fibrosis by suppressing the TLR4-TNF-α and SRB-NLRP3 pathways and further inhibiting the IL-17A-CXCL5-CXCR2 inflammatory axis. SRB: scavenger receptor B; NLPR3: NOD-like receptor thermal protein domain associated protein 3; TLR4: Toll-like receptor 4; TNF-α: tumor necrosis factor; IL-17A: interleukin-17A; CXCL5: CXC motif chemokine ligand 5; CXCR2: Chemokine (C-X-C motif) Receptor 2; 5-HT: serotonin; AKT: protein kinase B; LRP-6: low-density lipoprotein receptor-related proteins; H<sub>2</sub>S: hydrogen sulfide; TGF-β1: transforming growth factor-β1; smad: small mother decapentaplegic protein. Created with Figdraw (<a href="http://www.figdraw.com" target="_blank">www.figdraw.com</a>), license ID: PYPIP737ba.</p>
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<p>Mechanisms of exercise modulation of renal fibrosis. Exercise exerts its beneficial effects on renal fibrosis through various mechanisms: Exercise suppresses NOX4-dependent ROS production in the kidney, thereby inhibiting the NF-κB/NLPR3 inflammasome pathway, or by targeting Sirt1, which ultimately ameliorates renal fibrosis associated with diabetic nephropathy. Exercise inhibits the TGF-β/Smad pathway or reduces Ang II content, diminishes AT1R and Ang II binding, and inhibits the Ang II-AT1R-TGF-β pathway. These actions contribute to the mitigation of renal fibrosis development in hypertensive conditions. In aging kidneys, exercise improves renal fibrosis by inhibiting the TGF-β1/TAK1/MKK3/p38 MAPK signaling pathway, enhancing autophagy activity, and delaying the epithelial–mesenchymal transition, or activating PPAR α to reduce oxidative stress, inflammation, and lipid accumulation by inhibiting the expression of miR-21 and miR-34a. TGF-β1: transforming growth factor-β1; TAK1: transforming growth factor-β (TGF-β)-activated kinase 1; MKK3: mitogen-activated protein kinase (MAPK) kinase; p38MAPK: p38 mitogen-activated protein kinase; NOX4: NADPH oxidase 4; ROS: reactive oxygen species; NF-κB: nuclear factor kappa-B; NLPR3: NOD-like receptor thermal protein domain associated protein 3; AngⅡ: angiotensin II; AT1R: Ang II-angiotensin II type I receptor; α-SMA: α-smooth muscle actin; CTGF: connective tissue growth factor; Sirt1: silent information regulator 1; H<sub>2</sub>S: hydrogen sulfide; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1-α; miR-21: microRNA-21; miR-34a: microRNA-34a. Created with Figdraw (<a href="http://www.figdraw.com" target="_blank">www.figdraw.com</a>), license ID: TRPRT70cb4.</p>
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<p>Mechanisms of exercise modulation of myocardial fibrosis. Aging, myocardial infarction, metabolic diseases, and hypertension can all lead to myocardial fibrosis. Aging: Exercise reduces collagen deposition by enhancing MMP-2 activity and decreasing the expression of fibrosis-associated factors (TGF-β1, TIMP-1, COL-I). It also restores endogenous H<sub>2</sub>S levels or inhibits the FGF-2/uPA/MMP-2 signaling pathway. Metabolic diseases: Exercise inhibits the TGF-β1/Smad signaling pathway or reduces ROS production, promoting HO-1 expression and inhibiting fibrosis-related factors. Myocardial infarction: Exercise inhibits TGF-β1 signaling through the NRG-1/ErbB signaling pathway or by upregulating miR-29a, miR-101a, and FGF-21 expression. In addition, exercise can also secrete several myokines such as irisin, CHI3L1, and FSTL1 to ameliorate myocardial fibrosis after myocardial infarction. Hypertension: Exercise attenuates myocardial fibrosis by inhibiting the LOXL-2/TGF-β signaling pathway and the expression of AT1R and FGF23, or by promoting the expression of ccdc80tide and AMPKα1. MMP: matrix metallopeptidase; TGF-β1: transforming growth factor-β1; TIMP-1: tissue inhibitor of metal protease1; H2S: hydrogen sulfide; COL-Ⅰ: Collagen 1; FGF-2: fibroblast growth factor 2; uPA: urokinase-type plasminogen activator; NRG1: Neuregulin 1; FGF-21: fibroblast Growth Factor 21; miR-29a: microRNA-29a; miR-101a: microRNA-101a; smad: small mother decapentaplegic protein; ROS: reactive oxygen species; CTGF: connective tissue growth factor; HO-1: heme oxygenase 1; JAK: janus kinase 2; STAT3: signal transducer and activator of transcription 3; AMPKα1: AMP-activated protein kinase α1; Sirt1: silent information regulator 1; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1-α; AT1R: Ang II-angiotensin II type I receptor; FGF-23: fibroblast Growth Factor 23; LOXL2: Lysyl oxidase-like 2; miR-34a: microRNA-34a; miR-486a-5p: microRNA-486a-5p; miR-29: microRNA-29; miR-133: microRNA-133; TNF-α: tumor necrosis factor; NF-kB: nuclear factor kappa-B; AKT: protein kinase B; PI3K: phosphoinositide 3-kinase; ALCAT1: lysocardiolipin acyltransferase-1. Created with Figdraw (<a href="http://www.figdraw.com" target="_blank">www.figdraw.com</a>), license ID: PRPRW1c841.</p>
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<p>Antifibrotic mechanisms of exercise: Exercise exerts its anti-fibrotic effects by directly or indirectly (secreting exerkines or targeting microRNAs) affecting multiple signaling pathways associated with fibrogenesis. Created with Figdraw (<a href="http://www.figdraw.com" target="_blank">www.figdraw.com</a>), license ID: IYAUA656e8.</p>
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26 pages, 1014 KiB  
Article
Evaluation of Selected Pro- and Anti-Inflammatory Adipokines in Colostrum from Mothers with Gestational Diabetes Mellitus
by Jolanta Lis-Kuberka, Marta Berghausen-Mazur and Magdalena Orczyk-Pawiłowicz
Int. J. Mol. Sci. 2025, 26(1), 40; https://doi.org/10.3390/ijms26010040 - 24 Dec 2024
Viewed by 607
Abstract
Adipokines related to gestational diabetes mellitus (GDM) are an emerging area of interest. The aim of this study was to evaluate the associations between GDM and adipokine levels in human milk. This was an observational cohort study targeting mothers with gestational diabetes, which [...] Read more.
Adipokines related to gestational diabetes mellitus (GDM) are an emerging area of interest. The aim of this study was to evaluate the associations between GDM and adipokine levels in human milk. This was an observational cohort study targeting mothers with gestational diabetes, which evaluated the association of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment), with colostral adipokines involved in pro- and anti-inflammatory processes. Colostrum was collected from hyperglycemic (N = 34) and normoglycemic (N = 26) mothers, and adipokine levels were determined by immunoenzymatic assay. Among anti-inflammatory adipokines, only for irisin and vaspin, but not for obestatin and adropin, were significantly different levels noted between the GDM-G1, GDM-G2 and non-GDM cohorts. Colostrum of the GDM-G2 subgroup contained more vaspin (4.77 ng/mL) than that of normoglycemic mothers (3.12 ng/mL) and more irisin (26.95 μg/mL) than in the GDM-G1 subgroup (17.59 μg/mL). The levels of pro-inflammatory adipokines, namely, dermcidin, chemerin and visfatin, were at similar levels irrespective of maternal glycemia. Moreover, irisin showed a negative correlation with dermcidin in GDM-G2 and non-GDM cohorts. Associations were observed between colostral irisin and maternal preconception BMI, dermcidin and gestational age, and vaspin and maternal age. This study provides evidence that the way of restoring glucose homeostasis in pregnant women has an impact on the anti-inflammatory adipokines irisin and vaspin, but not on obestatin and adropin. GDM, regardless of severity, did not influence the colostral pro-inflammatory adipokines visfatin, chemerin and dermcidin. Full article
(This article belongs to the Special Issue Molecular Advances in Gestational Diabetes Mellitus)
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<p>Comparison of irisin (<b>A</b>), adropin (<b>B</b>), obestatin (<b>C</b>), visfatin (<b>D</b>), vaspin (<b>E</b>), chemerin (<b>F</b>) and dermcidin (<b>G</b>) concentrations in colostrum between gestational diabetic (G1 and G2) and normoglycemic (non-GDM) mothers. Data are given as mean and median values and 25th and 75th quartiles. A <span class="html-italic">p</span>-value lower than 0.05 was regarded as significant.</p>
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<p>Correlations between the concentration of adipokine in milk collected from GDM and non-GDM mothers and day of lactation, age, preconceptional BMI, and week of gestation. The Spearman correlation coefficient is represented in the heat map following the color in the legend. BMI—preconceptional body mass index; HBD—week of gestation. Bold frames represent correlations with statistical significance (<span class="html-italic">p</span> &lt; 0.05).</p>
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15 pages, 1181 KiB  
Review
Effects of Exercise Training on Cardiac Mitochondrial Functions in Diabetic Heart: A Systematic Review
by Iqbal Ali Shah, Shahid Ishaq, Shin-Da Lee and Bor-Tsang Wu
Int. J. Mol. Sci. 2025, 26(1), 8; https://doi.org/10.3390/ijms26010008 - 24 Dec 2024
Viewed by 594
Abstract
A diabetic heart is characterized by fibrosis, autophagy, oxidative stress, and altered mitochondrial functions. For this review, three databases (PubMed, EMBASE, and Web of Science) were searched for articles written in English from September 2023 to April 2024. Studies that used exercise training [...] Read more.
A diabetic heart is characterized by fibrosis, autophagy, oxidative stress, and altered mitochondrial functions. For this review, three databases (PubMed, EMBASE, and Web of Science) were searched for articles written in English from September 2023 to April 2024. Studies that used exercise training for at least 3 weeks and which reported positive, negative, or no effects were included. The CAMARADES checklist was used to assess the quality of the included studies, and ten studies (CAMARADES scores 4–7/10) were included. Nine studies showed that exercise training improved cardiac mitochondrial oxidative phosphorylation by decreasing ROS, increasing electron transport chain activity, and enhancing the production of ATP. Eight studies indicated that exercise training ameliorated mitochondrial biogenesis by increasing the levels of AMPK, PGC-1α, Akt, Irisin, and Sirtuin-III. Moreover, four studies focused on mitochondrial dynamics and concluded that exercise training helped decrease the levels of mitochondrial fission factor and dynamin-related protein- 1. Finally, six studies revealed improvements in mitochondrial physiological characteristics such as size, potential, and permeability. Our findings demonstrate the beneficial effects of exercise training on cardiac mitochondrial function in diabetic hearts. Exercise training improves cardiac mitochondrial physiological characteristics, oxidative phosphorylation, biogenesis, and dynamics. Full article
(This article belongs to the Special Issue Molecular Research on Diabetes and Obesity)
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<p>A PRISMA chart indicating the procedure for the inclusion of studies.</p>
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<p>The effects of exercise on cardiac mitochondrial function, including physiological characteristics, oxidative phosphorylation, biogenesis, and dynamics. This hypothesized figure shows how exercise training ameliorates mitochondrial functions by affecting different parameters. The physiological properties, including mitochondrial membrane potential, permeability, and mitochondrial size, decreased in diabetic hearts but increased with exercise training. Mitochondrial oxidative phosphorylation characteristics are also improved with exercise training; such improvements include increased SOD2, ATP, and complex activity, with decreased UCP2 and ROS levels. Mitochondrial biogenesis factors such as PGC1 and irisin activate AMPK, Tfam, and mt-DNA; these in turn improve biogenesis by reducing the expression of the mitochondrial Drp1, MFP1, and Fis1 factors. The blue arrow indicates increase with exercise training while the orange color indicates decrease in diabetic heart of the different parameters involved in mitochondrial function.</p>
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8 pages, 911 KiB  
Article
Biomarker Insights: Evaluation of Presepsin, Apelin, and Irisin Levels in Cutaneous Leishmaniasis
by Revsa Evin Canpolat-Erkan, Recep Tekin and Bilal Sula
Diagnostics 2024, 14(24), 2869; https://doi.org/10.3390/diagnostics14242869 - 20 Dec 2024
Viewed by 619
Abstract
Background/Objectives: Cutaneous leishmaniasis (CL) is a skin disease caused by Leishmania parasites. Presepsin, irisin, and apelin are biomarkers that are involved in the inflammatory response. The aim of this study was to investigate the association between serum levels of specific biomarkers, such [...] Read more.
Background/Objectives: Cutaneous leishmaniasis (CL) is a skin disease caused by Leishmania parasites. Presepsin, irisin, and apelin are biomarkers that are involved in the inflammatory response. The aim of this study was to investigate the association between serum levels of specific biomarkers, such as presepsin, apelin, and irisin, and the clinical features, location, number, and size of lesions in patients with CL. Methods: This study is a single-centre, prospective cohort study involving a total of 30 patients with skin lesions compatible with CL and 30 healthy matched controls. Age, sex, type of skin lesion, location of skin lesion, number of skin lesions, and diameter of skin lesions were recorded. The levels of presepsin, irisin, and apelin measured in the blood samples of the patient group were analysed in comparison to those in the healthy control group. Results: The findings revealed that presepsin levels were significantly elevated in the patient group compared to the controls (p = 0.000). However, no statistically significant differences were observed between the groups for irisin and apelin levels (p-values 0.096 and 0.836, respectively). A negative correlation was identified between presepsin levels and the number of skin lesions, the diameter of the largest lesion, and the total diameter of the lesions (p = 0.000). Conclusions: It appears that measuring presepsin levels in patients with CL may be beneficial. Presepsin has the potential to serve as a prognostic marker in CL, offering significant benefits in guiding clinicians in assessing disease progression and response to treatment. Full article
(This article belongs to the Special Issue Laboratory Diagnosis in Microbial Diseases, 2nd Edition)
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<p>Levels of presepsin in the CL group and the control group.</p>
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<p>Linear regression curves between the presepsin levels and the number of skin lesions, which showed significant correlations in Pearson’s correlation analysis. The presepsin levels showed a negative correlation with the number of skin lesions (r = −0.728; p = 0.000).</p>
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<p>The presepsin levels showed a negative correlation with the total diameter of the lesions (r = −0.695; p = 0.000).</p>
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13 pages, 795 KiB  
Article
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
by Tetiana A. Berezina, Oleksandr O. Berezin, Evgen V. Novikov, Michael Lichtenauer and Alexander E. Berezin
Biomolecules 2024, 14(12), 1615; https://doi.org/10.3390/biom14121615 - 17 Dec 2024
Viewed by 802
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue New Insights into Cardiometabolic Diseases)
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<p>Flowchart of the study design. Abbreviations: ACS, acute coronary syndrome; CV, cardiovascular; ESRD, end-stage renal disease; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; LVEF, left ventricular ejection fraction; MI, myocardial infarct; TNF-alpha, tumor necrosis factor-alpha; hs-CRP, high-sensitivity C-reactive protein; hs-TrT, high-sensitivity troponin T; NT-proBNP, N-terminal natriuretic pro-peptide.</p>
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<p>Kaplan–Meier curves for 3-year cumulative clinical endpoint. Abbreviations: OR, odds ratio; CI, confidence interval.</p>
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28 pages, 2534 KiB  
Review
Irisin: A Multifaceted Hormone Bridging Exercise and Disease Pathophysiology
by Ilaria Paoletti and Roberto Coccurello
Int. J. Mol. Sci. 2024, 25(24), 13480; https://doi.org/10.3390/ijms252413480 - 16 Dec 2024
Viewed by 1178
Abstract
The fibronectin domain-containing protein 5 (FNDC5), or irisin, is an adipo-myokine hormone produced during exercise, which shows therapeutic potential for conditions like metabolic disorders, osteoporosis, sarcopenia, obesity, type 2 diabetes, and neurodegenerative diseases, including Alzheimer’s disease (AD). This review explores its potential across [...] Read more.
The fibronectin domain-containing protein 5 (FNDC5), or irisin, is an adipo-myokine hormone produced during exercise, which shows therapeutic potential for conditions like metabolic disorders, osteoporosis, sarcopenia, obesity, type 2 diabetes, and neurodegenerative diseases, including Alzheimer’s disease (AD). This review explores its potential across various pathophysiological processes that are often considered independent. Elevated in healthy states but reduced in diseases, irisin improves muscle–adipose communication, insulin sensitivity, and metabolic balance by enhancing mitochondrial function and reducing oxidative stress. It promotes osteogenesis and mitigates bone loss in osteoporosis and sarcopenia. Irisin exhibits anti-inflammatory effects by inhibiting NF-κB signaling and countering insulin resistance. In the brain, it reduces amyloid-β toxicity, inflammation, and oxidative stress, enhancing brain-derived neurotrophic factor (BDNF) signaling, which improves cognition and synaptic health in AD models. It also regulates dopamine pathways, potentially alleviating neuropsychiatric symptoms like depression and apathy. By linking physical activity to systemic health, irisin emphasizes its role in the muscle–bone–brain axis. Its multifaceted benefits highlight its potential as a therapeutic target for AD and related disorders, with applications in prevention, in treatment, and as a complement to exercise strategies. Full article
(This article belongs to the Section Molecular Neurobiology)
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<p>Irisin has pleiotropic effects, as it exerts multiple, diverse biological actions in different tissues and organ systems, meaning its effects are not limited to one specific function but span several physiological processes that impact metabolism, muscle function, fat storage, bone health, and brain activity. In particular, in skeletal muscle, irisin triggers the (MAPK)-PGC-1α pathway, thus improving oxidative phosphorylation and consequently mitochondrial respiration, together with an increase in GLUT4 translocation. At the same time, in cardiac tissue, GLUT4 translocation appears downstream of the activation of the PI3K/PKB/Akt pathway, with the final result of improving glucose uptake. In relationship to the liver, downstream, the PI3K trigger Akt/GSK3 is then activated, leading to gluconeogenesis reduction and the concomitant induction of glycogen synthesis. Altogether, with the stimulation of all the aforementioned pathways, irisin can promote sensitization to glucose in insulin-dependent tissue, like the heart, skeletal muscle, and the liver (<b>pink lines</b>). This adipo-myokine plays a crucial role in the hepatic metabolism, as AMPK phosphorylation exerts anti-inflammatory potential by decreasing NLRP3 inflammasome and NFKβ (<b>green lines</b>). Through AMPK phosphorylation, irisin also participates in autophagic-related mechanisms via mTOR inhibition promoting osteoblastogenesis by the parallel activation of Wtn/β catenin signaling. Furthermore, irisin is involved in osteogenesis involving ERK signaling via p38 MAPK, the same pathway mediating GLUT4 translocation in muscle tissue (<b>blue lines</b>). Irisin plays a crucial role not only in muscle–bone crosstalk but also acts on many other peripheral organs. Moreover, irisin shows antioxidant effects in the intestine and pancreas, as it can upregulate UCP2, reducing both oxidative stress and ER stress in intestinal cells, additionally increasing mitochondrial function and biogenesis (<b>violet lines</b>). Interestingly, irisin exerts a protective action on pancreatic β-cells to stimulate insulin synthesis and glucose-induced insulin secretion. Specifically, irisin can block the apoptotic effects induced by selective saturated fatty acids in β-cells via the Akt and Bcl-2 signaling pathway (<b>red lines</b>). Lastly, irisin acts as antihypertensive hormone, since it reduces blood pressure by activating the hypothalamic factor Nrf2, having a more selective effect on PVN nuclei for its antioxidant and anti-inflammatory action. Thus, this hormone cannot be simply identified for its single effects on specific organs, since its beneficial activity is provided by the synergistic combination of its action on multiple organs and systems.</p>
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<p>Skeletal muscle and bone are dynamic, adaptable tissues that function as endocrine and paracrine organs, maintaining tight reciprocal control and communication. Osteoporosis and sarcopenia often co-exist in obese patients with visceral adiposity, a condition known as osteosarcopenic obesity. This figure illustrates how irisin helps counteract and rebalance these pathological conditions by promoting muscle growth and bone formation. Physical exercise increases circulating irisin levels, as well as PGC-1α and FNDC5, leading to beneficial effects on bone health, particularly by stimulating pro-osteoblastic mechanisms and enhancing bone formation. Adiposity, characterized as a state of chronic low-grade inflammation, involves excessive lipid infiltration in skeletal muscle, which induces lipotoxicity and inflammation associated with myosteatosis. This fat deposition triggers the release of pro-inflammatory cytokines, affecting the osteoprotegerin pathway and promoting osteoclastogenesis and bone resorption. Irisin, by reducing inflammation and lipotoxicity (indicated by green arrows), can decrease bone resorptive factors, activate the Wnt/β-catenin signaling pathway, and stimulate osteoblast differentiation. Lipid accumulation also contributes to insulin resistance. Irisin reduces adipose tissue inflammation, improving the inflammatory impact of lipid deposits and lowering the risk of insulin resistance. Since insulin signaling deficiency is linked to alterations in bone microarchitecture, β-cell dysfunction is associated with osteoporosis, highlighting the direct relationship between insulin resistance and bone metabolism. Irisin acts as a hormonal messenger capable of counteracting insulin resistance and myosteatosis, thereby connecting insulin metabolism with muscle and bone homeostasis. Specifically, irisin can decrease NLRP3 inflammasome activity, promote GLUT4 translocation in muscle, and upregulate GLUT4 via the AMPK signaling pathway.</p>
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<p>The figure depicts the capacity of irisin to affect multiple pathways involved in age-associated neurodegeneration and mechanisms underlying AD pathogenesis. Irisin serves as a crucial link between muscle contraction, myokine secretion, and brain function, embodying the concept of the muscle–brain axis. It has been shown to have potent (1) anti-inflammatory and (2) neuroprotective effects, such as protecting against Aβ neurotoxicity, reducing the release of pro-inflammatory cytokines, like IL-1β and IL-6, and inhibiting the expression of COX-2 and NF-κB in astrocytes. Irisin’s neuroprotective actions extend to preventing neuronal damage in conditions like middle cerebral artery occlusion and brain infarction, as well as mitigating microglial activation, neutrophil infiltration, and the expression of TNF-α and IL-6 via the ERK1/2 and Akt signaling pathways. Additionally, it counters the TLR4/MyD88-mediated neuroinflammatory response. The integrin αV/β5 receptor, which is highly expressed in microglia, plays a key role in irisin’s effects. Irisin has been shown to promote the shift from an M1 pro-inflammatory phenotype to an M2-like anti-inflammatory phenotype in microglia, leading to changes in their morphology. This shift is associated with an increase in AMPK phosphorylation and the expression of the anti-apoptotic protein Bcl-2. The interaction between irisin and BDNF signaling is also essential in neurodegenerative diseases, particularly Alzheimer’s disease (AD). For example, FNDC5 overexpression can mitigate the inhibitory effects of Aβ<sub>1-42</sub> oligomers on BDNF expression. Exercise has been linked to increased (3) lactate levels and elevated hippocampal BDNF expression, with SIRT1 histone deacetylase activating the PGC-1α/FNDC5 signaling pathway to induce BDNF expression. Irisin’s (3) antidepressant potential is particularly relevant for managing neuropsychiatric symptoms in AD. Its ability to enhance dopaminergic activity (i.e., right side of the figure) may help address the pathophysiology of depression. Specifically, irisin-induced BDNF expression can activate dopamine D3 receptor-mediated signaling through the Akt and ERK pathways, fine-tuning dopamine release and contributing to a reduction in Aβ deposits and the overall Aβ burden.</p>
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12 pages, 447 KiB  
Article
Effect of Low- and Moderate-Intensity Aerobic Training on Body Composition Cardiorespiratory Functions, Biochemical Risk Factors and Adipokines in Morbid Obesity
by Judit Horváth, Ildikó Seres, György Paragh, Péter Fülöp and Zoltán Jenei
Nutrients 2024, 16(23), 4251; https://doi.org/10.3390/nu16234251 - 9 Dec 2024
Viewed by 906
Abstract
Background: Obesity poses an enormous public health and economic burden worldwide. Visceral fat accumulation is associated with various metabolic and cardiovascular consequences, resulting in an increased prevalence of atherosclerotic conditions. We aimed to examine the impact of low-and moderate-intensity aerobic training on several [...] Read more.
Background: Obesity poses an enormous public health and economic burden worldwide. Visceral fat accumulation is associated with various metabolic and cardiovascular consequences, resulting in an increased prevalence of atherosclerotic conditions. We aimed to examine the impact of low-and moderate-intensity aerobic training on several anthropometric and cardiorespiratory parameters and markers of atherosclerosis, including inflammation, serum levels of lipoproteins and adipokines of extremely obese patients in poor condition. Methods: Forty severely obese patients were recruited and randomized into two groups, Group 1 and Group 2, for a six-week inpatient study. Group 1 received moderate-intensity (40–60% heart rate reserve) and Group 2 received low-intensity (30–39% of heart rate reserve) aerobic training combined with resistance training. The patients’ cardiorespiratory functions were assessed by ergospirometry. Anthropometric data were recorded, body composition was analyzed and functional tests were performed. We also investigated serum lipids and high-sensitive C-reactive protein levels and calculated the homeostatic model assessment-insulin resistance indices and adipokine levels as predictive biomarkers. Results: Functional abilities and some biochemical parameters, such as homeostatic model assessment-insulin resistance, serum lipids, apolipoprotein A and apolipoprotein-B improved in both groups in a positive direction. However, cardiorespiratory capacity and the serum levels of high-sensitive C-reactive protein and Lipocalin-2 decreased, while irisin and paraoxonase 1 increased significantly, but only in Group 1. Conclusions: Six weeks of aerobic training, regardless of its intensity, could induce favorable changes in functional tests, body composition and serum lipids, even in severely obese, extremely unconditioned patients in both groups. However, moderate-intensity aerobic training should at least increase cardiorespiratory capacity and yield a better lipid profile oxidative status and inflammation profile. Full article
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<p>Timeline.</p>
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25 pages, 1456 KiB  
Review
Obesity, Osteoarthritis, and Myokines: Balancing Weight Management Strategies, Myokine Regulation, and Muscle Health
by Daniel Vasile Timofte, Razvan Cosmin Tudor, Veronica Mocanu and Luminita Labusca
Nutrients 2024, 16(23), 4231; https://doi.org/10.3390/nu16234231 - 7 Dec 2024
Viewed by 1461
Abstract
Obesity and osteoarthritis (OA) are increasingly prevalent conditions that are intricately linked, with each exacerbating the other’s pathogenesis and worsening patient outcomes. This review explores the dual impact of obesity on OA, highlighting the role of excessive weight in aggravating joint degeneration and [...] Read more.
Obesity and osteoarthritis (OA) are increasingly prevalent conditions that are intricately linked, with each exacerbating the other’s pathogenesis and worsening patient outcomes. This review explores the dual impact of obesity on OA, highlighting the role of excessive weight in aggravating joint degeneration and the limitations OA imposes on physical activity, which further perpetuates obesity. The role of muscle tissue, particularly the release of myokines during physical activity, is examined in the context of OA and obesity. Myokines such as irisin, IL-6, and myostatin are discussed for their roles in metabolic regulation, inflammation, and tissue repair, offering insights into their potential therapeutic targets. This review emphasizes the importance of supervised weight management methods in parallel with muscle rehabilitation in improving joint health and metabolic balance. The potential for myokine modulation through targeted exercise and weight loss interventions to mitigate the adverse effects of obesity and OA is also discussed, suggesting avenues for future research and therapy development to reduce the burden of these chronic conditions. Full article
(This article belongs to the Special Issue Nutritional Management and Body Composition after Bariatric Surgery)
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<p>Sedentary life and obesity are associated with muscle inactivity/waste and predominance of pro-inflammatory status and catabolic myokines (such as Il-6 and myostatin), favoring occurrence and progression of osteoarthritis. Lean mass, brown adipose tissue, and physical activity increase predominance of anabolic myokines (such as irisin, BAIBA, myonectin, and FGF21) contributing to joint health. Ascending arrows signify increased myokine/cytokine expression. More evidence is needed to understand impact of different types of weight management strategies including physical activity on muscle mass, myokine release, and articular joint and overall health.</p>
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16 pages, 6140 KiB  
Article
Alterations in Biomarkers Associated with Cardiovascular Health and Obesity with Short-Term Lifestyle Changes in Overweight Women: The Role of Exercise and Diet
by Nezihe Şengün, Ragıp Pala, Vedat Çınar, Taner Akbulut, Alin Larion, Johnny Padulo, Luca Russo and Gian Mario Migliaccio
Medicina 2024, 60(12), 2019; https://doi.org/10.3390/medicina60122019 - 7 Dec 2024
Viewed by 901
Abstract
Background and Objectives: In this study, the effects of an eight-week exercise and nutrition program on blood lipids, glucose, insulin, insulin resistance (HOMA-IR), leptin, ghrelin, irisin, malondialdehyde (MDA), and Growth Differentiation Factor 15 (GDF15) in overweight women were investigated. Materials and Methods: [...] Read more.
Background and Objectives: In this study, the effects of an eight-week exercise and nutrition program on blood lipids, glucose, insulin, insulin resistance (HOMA-IR), leptin, ghrelin, irisin, malondialdehyde (MDA), and Growth Differentiation Factor 15 (GDF15) in overweight women were investigated. Materials and Methods: A total of 48 women volunteers participated in this study. The participants were randomly divided into four groups: control (C), exercise (E), nutrition (N), exercise + nutrition (E + N). While no intervention was applied to group C, the other groups participated in the predetermined programs for 8 weeks. At the beginning and end of this study, body composition was measured and blood samples were taken. Results: It was determined that the body composition components, lipid profile indicators, insulin, glucose, insulin resistance, leptin, ghrelin, irisin, and MDA parameters examined in this study showed positive changes in the intervention groups. Group E had a greater effect on body muscle percentage, MDA, and irisin levels, while group N had a greater effect on blood lipids and ghrelin levels. Conclusions: As a result, it is thought that lifestyle changes are important to improve cardiovascular health and combat obesity, and that maintaining a healthy diet together with exercise may be more effective. Full article
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<p>Research design.</p>
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<p>Correlation between some serum parameters (Insulin (μIU/mL), Leptin (ng/mL), ghrelin (pg/mL), irisin (ng/mL), GDF15: Growth Differentiation Factor 15 (ng/L), MDA: malondialdehyde (nmol/mL).</p>
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