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Minuti A, Raffaele I, Scuruchi M, Lui M, Muscarà C, Calabrò M. Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases. Antioxidants (Basel) 2025; 14:554. [PMID: 40427436 PMCID: PMC12108254 DOI: 10.3390/antiox14050554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2025] [Revised: 04/28/2025] [Accepted: 05/05/2025] [Indexed: 05/29/2025] Open
Abstract
Irisin is a peptide derived from fibronectin type III domain-containing protein 5 (FNDC5) and is primarily produced by muscle fibers under the regulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) during exercise. Irisin has been the subject of extensive research due to its potential as a metabolic regulator and its antioxidant properties. Notably, it has been associated with protective actions within the brain. Despite growing interest, many questions remain regarding the molecular mechanisms underlying its effects. This review summarizes recent findings on irisin, highlighting its pleiotropic functions and the biological processes and molecular cascades involved in its action, with a particular focus on the central nervous system. Irisin plays a crucial role in neuron survival, differentiation, growth, and development, while also promoting mitochondrial homeostasis, regulating apoptosis, and facilitating autophagy-processes essential for normal neuronal function. Emerging evidence suggests that irisin may improve conditions associated with non-communicable neurological diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and multiple sclerosis. Given its diverse benefits, irisin holds promise as a novel therapeutic agent for preventing and treating neurological diseases.
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Affiliation(s)
- Aurelio Minuti
- IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy; (A.M.); (M.C.)
| | - Ivana Raffaele
- IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy; (A.M.); (M.C.)
| | - Michele Scuruchi
- Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy;
| | - Maria Lui
- IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy; (A.M.); (M.C.)
| | - Claudia Muscarà
- IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy; (A.M.); (M.C.)
| | - Marco Calabrò
- IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy; (A.M.); (M.C.)
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Garutti M, Sirico M, Noto C, Foffano L, Hopkins M, Puglisi F. Hallmarks of Appetite: A Comprehensive Review of Hunger, Appetite, Satiation, and Satiety. Curr Obes Rep 2025; 14:12. [PMID: 39849268 DOI: 10.1007/s13679-024-00604-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/18/2024] [Indexed: 01/25/2025]
Abstract
PURPOSE OF REVIEW The present review describes the available literature on the physiologic mechanisms that modulate hunger, appetite, satiation, and satiety with a particular focus on well-established and emerging factors involved in the classic satiety cascade model. RECENT FINDING Obesity is a significant risk factor for numerous chronic conditions like cancer, cardiovascular diseases, and diabetes. As excess energy intake is considered by some to be the primary driver of weight gain, tremendous collective effort should be directed toward reducing excessive feeding at the individual and population levels. From this perspective, detailed understanding of physiologic mechanisms that control appetite, and in turn, the design of effective interventions to manage appetite, may represent key strategies in controlling the obesity epidemic. With the obesity's prevalence on the rise worldwide, research on hunger, appetite, satiation and satiety is more relevant than ever. This research aims to provide practical insights for medical practitioners, nutrition professionals, and the broader scientific community in the fight against this global health challenge.
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Affiliation(s)
- Mattia Garutti
- CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy.
| | - Marianna Sirico
- Medical Oncology and Breast Unit, IRCCS Istituto Romagnolo Per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Forli-Cesena, Italy
| | - Claudia Noto
- Medical Oncology, Azienda Sanitaria Universitaria Integrata Di Trieste, Ospedale Maggiore, Piazza Dell'Ospitale 1, 34125, Trieste, Italy
| | - Lorenzo Foffano
- CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
- Department of Medicine, University of Udine, 33100, Udine, Italy
| | - Mark Hopkins
- School of Food Science & Nutrition, University of Leeds, Leeds, LS2 9JT, UK
| | - Fabio Puglisi
- CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy
- Department of Medicine, University of Udine, 33100, Udine, Italy
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Ferara N, Balta V, Đikić D, Odeh D, Mojsović-Ćuić A, Feher Turković L, Dilber D, Beletić A, Landeka Jurčević I, Šola I. The Effect of the Glucosinolate Sinigrin on Alterations in Molecular Biomarkers of the Myocardium in Swiss Mice. Foods 2025; 14:327. [PMID: 39856994 PMCID: PMC11765020 DOI: 10.3390/foods14020327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/27/2024] [Accepted: 01/14/2025] [Indexed: 01/27/2025] Open
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 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.
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Affiliation(s)
- Nikola Ferara
- Department of Dermatology and Venereology, Sestre Milosrdnice University Hospital Centre, Vinogradska cesta 29, 10000 Zagreb, Croatia;
| | - Vedran Balta
- Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia
| | - Domagoj Đikić
- Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia
| | - Dyana Odeh
- Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia
| | - Ana Mojsović-Ćuić
- School of Applied Health Sciences, University of Zagreb, Mlinarska cesta 38, 10000 Zagreb, Croatia
| | - Lana Feher Turković
- School of Applied Health Sciences, University of Zagreb, Mlinarska cesta 38, 10000 Zagreb, Croatia
| | - Dario Dilber
- Department of Cardiology, Thalassotherapia Opatija, Maršala Tita 188, 51410 Opatija, Croatia;
| | - Anđelo Beletić
- Laboratory of Proteomics, Internal Diseases Clinic, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia
| | - Irena Landeka Jurčević
- Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia
| | - Ivana Šola
- Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb, Croatia
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López-Ojeda W, Hurley RA. Myokines and the Brain: A Novel Neuromuscular Endocrine Loop. J Neuropsychiatry Clin Neurosci 2025; 37:A4-4. [PMID: 39812655 DOI: 10.1176/appi.neuropsych.20240173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Affiliation(s)
- Wilfredo López-Ojeda
- Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center and the Research and Academic Affairs Service Line, W. G. Hefner Veterans Affairs Medical Center, Salisbury, N.C. (López-Ojeda, Hurley); Department of Psychiatry and Behavioral Medicine (López-Ojeda, Hurley) and Department of Radiology (Hurley), Wake Forest University School of Medicine, Winston-Salem, N.C
| | - Robin A Hurley
- Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center and the Research and Academic Affairs Service Line, W. G. Hefner Veterans Affairs Medical Center, Salisbury, N.C. (López-Ojeda, Hurley); Department of Psychiatry and Behavioral Medicine (López-Ojeda, Hurley) and Department of Radiology (Hurley), Wake Forest University School of Medicine, Winston-Salem, N.C
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Rooban S, Arul Senghor K, Vinodhini V, Kumar J. Adropin: A crucial regulator of cardiovascular health and metabolic balance. Metabol Open 2024; 23:100299. [PMID: 39045137 PMCID: PMC11263719 DOI: 10.1016/j.metop.2024.100299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 06/26/2024] [Accepted: 06/26/2024] [Indexed: 07/25/2024] Open
Abstract
Adropin, a peptide discovered in 2008, has gained recognition as a key regulator of cardiovascular health and metabolic balance. Initially identified for its roles in energy balance, lipid metabolism, and glucose regulation, adropin has also been found to improve cardiovascular health by enhancing endothelial function, modulating lipid profiles, and reducing oxidative stress. These protective mechanisms suggest that adropin may be able to help prevent conditions such as atherosclerosis, hypertension, and other cardiovascular diseases. Research has established connections between adropin and cardiovascular risk factors, such as obesity, insulin resistance, and dyslipidemia, positioning it as a valuable biomarker for evaluating cardiovascular disease risk. New studies highlight adropin's diagnostic and prognostic significance, showing that higher levels are linked to better cardiovascular outcomes, while lower levels are associated with a higher risk of cardiovascular diseases. This review aims to summarize current knowledge on adropin, emphasizing its significance as a promising focus in the intersection of cardiovascular health and metabolic health. By summarizing the latest research findings, this review aims to offer insights into the potential applications of adropin in both clinical practice and research, leading to a deeper understanding of its role in maintaining cardiovascular and metabolic health.
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Affiliation(s)
- S. Rooban
- Department of Biochemistry, SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, 603203, Kanchipuram, Chennai, Tamil Nadu, India
| | - K.A. Arul Senghor
- Department of Biochemistry, SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, 603203, Kanchipuram, Chennai, Tamil Nadu, India
| | - V.M. Vinodhini
- Department of Biochemistry, SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, 603203, Kanchipuram, Chennai, Tamil Nadu, India
| | - J.S. Kumar
- Department of General Medicine, SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, 603203, Kanchipuram, Chennai, Tamil Nadu, India
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Sun Z, Wu Z, Zhu L, Li X, Xu D, Tian X, Mao D. Research trends and hotspot evolution of exercise-regulated myokines: a bibliometric analysis from 2003 to 2023. Front Physiol 2024; 15:1410068. [PMID: 39148743 PMCID: PMC11324543 DOI: 10.3389/fphys.2024.1410068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 07/04/2024] [Indexed: 08/17/2024] Open
Abstract
Background The lack of physical activity is a common issue in modern society and is considered a major risk factor for various chronic non-communicable diseases. Bioactive factors secreted by skeletal muscle during exercise play a crucial role in inter-organ interactions. Since the concept of "myokines" was proposed in 2004, hundreds of regulatory myokines have been identified. Visual analysis of research on exercise-regulated myokines is significant to explore research hotspots and frontiers in this field. Methods Research literature on exercise-regulated myokines from 2003 to 2023 in the "Web of Science" database was used as the data source. Knowledge maps were drawn using "VOS Viewer, CiteSpace, and R-bibliometrix" software. Results A total of 1,405 papers were included, showing a fluctuating yet slow growth in annual publications. The United States and China led in the number of publications and collaboration networks. Harvard University ranked first with 120 publications. CIBER (centrality 0.16) and the University of California System (centrality 0.16) were pivotal in advancing this field. PEDERSEN BK led author rankings with 41 publications and 1,952 citations. FRONTIERS IN PHYSIOLOGY ranked first among journals with 64 publications and the highest g-index (39), while PLoS One had the highest h-index (25) and most citations (2,599). Key co-cited reference clusters included #1 skeletal muscle dysfunction, #2 obesity, #6 ASCs, and #7 adaptive immunocytes. Pontus Boström's paper had a notable citation burst intensity of 77.37. High-frequency keywords were "exercise" (509), "skeletal muscle" (452), and "expression" (293), with long-term keywords such as #0 irisin, #2 insulin resistance, #3 transcription, and #6 physical activity. Recently, keywords like "physical exercise," "resistance exercise," "aerobic exercise," "insulin," and "oxidative stress" have emerged. Conclusion Research in the field of exercise-regulated myokines shows an overall upward trend. The focus areas include myokines mediated by different types of exercise, the interaction of irisin-mediated muscle with other organs, and the important role of myokine-mediated oxidative stress in exercise simulation.
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Affiliation(s)
- Zhiyuan Sun
- College of Sports Science, Qufu Normal University, Qufu, Shandong, China
- Institute of Sports Science, Shandong Sport University, Jinan, Shandong, China
| | - Zekai Wu
- Graduate Education College, Shandong Sport University, Jinan, Shandong, China
| | - Lei Zhu
- College of Sports Science, Qufu Normal University, Qufu, Shandong, China
| | - Xinhe Li
- Graduate Education College, Shandong Sport University, Jinan, Shandong, China
| | - Dongdong Xu
- Graduate Education College, Shandong Sport University, Jinan, Shandong, China
| | - Xuewen Tian
- Institute of Sports Science, Shandong Sport University, Jinan, Shandong, China
- Graduate Education College, Shandong Sport University, Jinan, Shandong, China
| | - Dewei Mao
- College of Sports Science, Qufu Normal University, Qufu, Shandong, China
- Institute of Sports Science, Shandong Sport University, Jinan, Shandong, China
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Sheptulina AF, Yafarova AA, Mamutova EM, Drapkina OM. Sonographic Features of Rectus Femoris Muscle in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease and Their Correlation with Body Composition Parameters and Muscle Strength: Results of a Single-Center Cross-Sectional Study. Biomedicines 2024; 12:1684. [PMID: 39200149 PMCID: PMC11351426 DOI: 10.3390/biomedicines12081684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/15/2024] [Accepted: 07/24/2024] [Indexed: 09/01/2024] Open
Abstract
This study aimed to describe sonographic features of rectus femoris muscle (RFM) in patients with metabolic dysfunction-associated fatty liver disease (MASLD) and their correlation with body composition parameters and muscle strength. A total of 67 patients with MASLD underwent dual-energy X-ray absorptiometry (DEXA), bioimpedance analysis (BIA), muscle strength measurement (grip strength [GS] and chair stand test [CST]), and ultrasound (US) investigation of the RFM in the dominant thigh using a 4 to 18 MHz linear probe. MASLD patients exhibited increased RFM echogenicity, possibly due to fatty infiltration. We confirmed that the greater the subcutaneous fat thickness, the smaller was the muscle mass (p < 0.001), and the lower was the muscle strength (p < 0.001 for GS and p = 0.002 for CST). On the contrary, the greater the anteroposterior diameter (APD) of RFM, the higher was the muscle mass (p < 0.001), and the greater was the muscle strength (p < 0.001 for GS and p = 0.007 for CST). In addition, APD of the RFM and stiffness of RFM exhibited direct correlation with bone mineral density values of the lumbar spine (p = 0.005 for both GS and CST). We concluded that US investigation of the RFM in the dominant thigh can be helpful in identifying MASLD patients at a high risk of musculoskeletal disorders given repeated point-of-care clinical evaluations.
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Affiliation(s)
- Anna F. Sheptulina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia; (A.A.Y.); (E.M.M.); (O.M.D.)
| | - Adel A. Yafarova
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia; (A.A.Y.); (E.M.M.); (O.M.D.)
| | - Elvira M. Mamutova
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia; (A.A.Y.); (E.M.M.); (O.M.D.)
| | - Oxana M. Drapkina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia; (A.A.Y.); (E.M.M.); (O.M.D.)
- Department of Therapy and Preventive Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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Li D, Zhang T, Guo Y, Bi C, Liu M, Wang G. Biological impact and therapeutic implication of tumor-associated macrophages in hepatocellular carcinoma. Cell Death Dis 2024; 15:498. [PMID: 38997297 PMCID: PMC11245522 DOI: 10.1038/s41419-024-06888-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 06/26/2024] [Accepted: 07/02/2024] [Indexed: 07/14/2024]
Abstract
The tumor microenvironment is a complex space comprised of normal, cancer and immune cells. The macrophages are considered as the most abundant immune cells in tumor microenvironment and their function in tumorigenesis is interesting. Macrophages can be present as M1 and M2 polarization that show anti-cancer and oncogenic activities, respectively. Tumor-associated macrophages (TAMs) mainly have M2 polarization and they increase tumorigenesis due to secretion of factors, cytokines and affecting molecular pathways. Hepatocellular carcinoma (HCC) is among predominant tumors of liver that in spite of understanding its pathogenesis, the role of tumor microenvironment in its progression still requires more attention. The presence of TAMs in HCC causes an increase in growth and invasion of HCC cells and one of the reasons is induction of glycolysis that such metabolic reprogramming makes HCC distinct from normal cells and promotes its malignancy. Since M2 polarization of TAMs stimulates tumorigenesis in HCC, molecular networks regulating M2 to M1 conversion have been highlighted and moreover, drugs and compounds with the ability of targeting TAMs and suppressing their M2 phenotypes or at least their tumorigenesis activity have been utilized. TAMs increase aggressive behavior and biological functions of HCC cells that can result in development of therapy resistance. Macrophages can provide cell-cell communication in HCC by secreting exosomes having various types of biomolecules that transfer among cells and change their activity. Finally, non-coding RNA transcripts can mainly affect polarization of TAMs in HCC.
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Affiliation(s)
- Deming Li
- Department of Anesthesiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, PR China
| | - Ting Zhang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, 110001, PR China
| | - Ye Guo
- Department of Intervention, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, PR China
| | - Cong Bi
- Department of Radiology, The First Hospital of China Medical University, Shenyang, 110001, PR China.
| | - Ming Liu
- Department of Oral Radiology, School of Stomatology, China Medical University, Shenyang, Liaoning, 110002, PR China.
| | - Gang Wang
- Department of Intervention, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, PR China.
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Li H, Qin S, Tang J, Wang T, Ren W, Di L, Bo W, Ma Y, Wu F, Xu Z, Song W, Cai M, Xi Y, Tian Z. Resistance exercise upregulates Irisin expression and suppresses myocardial fibrosis following myocardial infarction via activating AMPK-Sirt1 and inactivating TGFβ1-Smad2/3. Acta Physiol (Oxf) 2024; 240:e14163. [PMID: 38752665 DOI: 10.1111/apha.14163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 04/23/2024] [Accepted: 04/24/2024] [Indexed: 06/09/2024]
Abstract
AIM To reveal the contribution of Irisin in the beneficial effects of resistance exercise on myocardial fibrosis (MF) and cardiac function in the mice with myocardial infarction (MI). METHODS The MI model was built by ligating the left anterior descending coronary artery in Fndc5 knockout mice (Fndc5-/-). Resistance exercise was started one week after surgery and continued for four weeks. In addition, H2O2, AICAR, recombinant human Irisin protein (rhIRISIN), and Sirt1 shRNA lentivirus (LV-Sirt1 shRNA) were used to intervene primary isolated cardiac fibroblasts (CFs). MF was observed through Masson staining, and apoptosis was assessed using TUNEL staining. MDA and T-SOD contents were detected by biochemical kits. The expression of proteins and genes was detected by Western blotting and RT-qPCR. RESULTS Resistance exercise increased Fndc5 mRNA level, inhibited the activation of TGFβ1-TGFβR2-Smad2/3 pathway, activated AMPK-Sirt1 pathway, reduced the levels of oxidative stress, apoptosis, and MF in the infarcted heart, and promoted cardiac function. However, Fndc5 knockout attenuated the protective effects of resistance exercise on the MI heart. Results of the in vitro experiments showed that AICAR and rhIRISIN intervention activated the AMPK-Sirt1 pathway and inactivated the TGFβ1-Smad2/3 pathway, and promoted apoptosis in H2O2-treated CFs. Notably, these effects of rhIRISIN intervention, except for the TGFβR2 expression, were attenuated by LV-Sirt1 shRNA. CONCLUSION Resistance exercise upregulates Fndc5 expression, activates AMPK-Sirt1 pathway, inhibits the activation of TGFβ1-Smad2/3 pathway, attenuates MF, and promotes cardiac function after MI.
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Affiliation(s)
- Hangzhuo Li
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Shuguang Qin
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
| | - Jie Tang
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
| | - Tao Wang
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
| | - Wujing Ren
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
| | - Lingyun Di
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
| | - Wenyan Bo
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
| | - Yixuan Ma
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
| | - Fangnan Wu
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Zujie Xu
- The Department of Physical Education, School of Physical Education, Taiyuan University of Technology, Taiyuan, China
| | - Wei Song
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
| | - Mengxin Cai
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
| | - Yue Xi
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
| | - Zhenjun Tian
- Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an, China
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Bilski J, Schramm-Luc A, Szczepanik M, Mazur-Biały AI, Bonior J, Luc K, Zawojska K, Szklarczyk J. Adipokines in Rheumatoid Arthritis: Emerging Biomarkers and Therapeutic Targets. Biomedicines 2023; 11:2998. [PMID: 38001998 PMCID: PMC10669400 DOI: 10.3390/biomedicines11112998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 11/05/2023] [Accepted: 11/06/2023] [Indexed: 11/26/2023] Open
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease manifested by joint involvement, extra-articular manifestations, and general symptoms. Adipose tissue, previously perceived as an inert energy storage organ, has been recognised as a significant contributor to RA pathophysiology. Adipokines modulate immune responses, inflammation, and metabolic pathways in RA. Although most adipokines have a pro-inflammatory and aggravating effect on RA, some could counteract this pathological process. The coexistence of RA and sarcopenic obesity (SO) has gained attention due to its impact on disease severity and outcomes. Sarcopenic obesity further contributes to the inflammatory milieu and metabolic disturbances. Recent research has highlighted the intricate crosstalk between adipose tissue and skeletal muscle, suggesting potential interactions between these tissues in RA. This review summarizes the roles of adipokines in RA, particularly in inflammation, immune modulation, and joint destruction. In addition, it explores the emerging role of adipomyokines, specifically irisin and myostatin, in the pathogenesis of RA and their potential as therapeutic targets. We discuss the therapeutic implications of targeting adipokines and adipomyokines in RA management and highlight the challenges and future directions for research in this field.
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Affiliation(s)
- Jan Bilski
- Department of Biomechanics and Kinesiology, Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-008 Krakow, Poland; (A.I.M.-B.); (K.Z.)
| | - Agata Schramm-Luc
- Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Krakow, Poland; (A.S.-L.); (K.L.)
| | - Marian Szczepanik
- Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-034 Krakow, Poland;
| | - Agnieszka Irena Mazur-Biały
- Department of Biomechanics and Kinesiology, Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-008 Krakow, Poland; (A.I.M.-B.); (K.Z.)
| | - Joanna Bonior
- Department of Medical Physiology, Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-126 Krakow, Poland; (J.B.); (J.S.)
| | - Kevin Luc
- Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Krakow, Poland; (A.S.-L.); (K.L.)
| | - Klaudia Zawojska
- Department of Biomechanics and Kinesiology, Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-008 Krakow, Poland; (A.I.M.-B.); (K.Z.)
| | - Joanna Szklarczyk
- Department of Medical Physiology, Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-126 Krakow, Poland; (J.B.); (J.S.)
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11
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Mohsin S, Brock F, Kaimala S, Greenwood C, Sulaiman M, Rogers K, Adeghate E. A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT. PeerJ 2023; 11:e16278. [PMID: 37868046 PMCID: PMC10588705 DOI: 10.7717/peerj.16278] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 09/20/2023] [Indexed: 10/24/2023] Open
Abstract
Background Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone 'irisin' in low dosage has been shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation, and inhibiting apoptosis and inflammation. We investigated the role of irisin in treating diabetic osteopathy by observing its effect on trabecular bone. Methods DM1 was induced by intraperitoneal injection of streptozotocin 60 mg/kg body weight. Irisin in low dosage (5 µg twice a week for 6 weeks I/P) was injected into half of the control and 4-week diabetic male Wistar rats. Animals were sacrificed six months after induction of diabetes. The trabecular bone in the femoral head and neck was analyzed using a micro-CT technique. Bone turnover markers were measured using ELISA, Western blot, and RT-PCR techniques. Results It was found that DM1 deteriorates the trabecular bone microstructure by increasing trabecular separation (Tb-Sp) and decreasing trabecular thickness (Tb-Th), bone volume fraction (BV/TV), and bone mineral density (BMD). Irisin treatment positively affects bone quality by increasing trabecular number p < 0.05 and improves the BMD, Tb-Sp, and BV/TV by 21-28%. The deterioration in bone microarchitecture is mainly attributed to decreased bone formation observed as low osteocalcin and high sclerostin levels in diabetic bone samples p < 0.001. The irisin treatment significantly suppressed the serum and bone sclerostin levels p < 0.001, increased the serum CTX1 levels p < 0.05, and also showed non-significant improvement in osteocalcin levels. Conclusions This is the first pilot study to our knowledge that shows that a low dose of irisin marginally improves the trabecular bone in DM1 and is an effective peptide in reducing sclerostin levels.
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Affiliation(s)
- Sahar Mohsin
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abudhabi, United Arab Emirates
| | - Fiona Brock
- Cranfield Forensic Institute, Cranfield University, Shrivenham, United Kingdom
| | - Suneesh Kaimala
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abudhabi, United Arab Emirates
| | - Charlene Greenwood
- School of Chemical and Physical Sciences, Keele University, Newcastle-under-Lyme, Staffordshire, United Kingdom
| | - Mohsin Sulaiman
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abudhabi, United Arab Emirates
| | - Keith Rogers
- Cranfield Forensic Institute, Cranfield University, Shrivenham, United Kingdom
| | - Ernest Adeghate
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abudhabi, United Arab Emirates
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Alipoor E, Hosseinzadeh-Attar MJ, Vasheghani-Farahani A, Salmani M, Rezaei M, Namkhah Z, Ahmadpanahi M, Jenab Y, Alidoosti M, Yaseri M. The relationship of circulating neuregulin 4 and irisin, and traditional and novel cardiometabolic risk factors with the risk and severity of coronary artery disease. Cytokine 2023; 170:156314. [PMID: 37591135 DOI: 10.1016/j.cyto.2023.156314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 06/02/2023] [Accepted: 07/31/2023] [Indexed: 08/19/2023]
Abstract
BACKGROUND AND AIMS Neuregulin 4 (NRG4) and irisin are adipokines that have been suggested to be associated with cardiometabolic risk factors and coronary artery disease (CAD), but the data are inconclusive. This study aimed to investigate the relationship between circulating NRG4 and irisin and cardiometabolic risk factors with CAD risk and severity. METHODS AND RESULTS In this cross-sectional study, the presence of CAD and the severity of stenosis (gensini score) were documented based on coronary angiography in 166 adults. Circulating NRG4 and irisin, glucose homeostasis markers, hs-CRP, lipid profiles, blood pressure, and anthropometric measurements were assessed as well. Age (p = 0.005), sex (p = 0.008), SBP (p = 0.033), DBP (p = 0.04), MAP (p = 0.018), FBG (p = 0.012), insulin (p = 0.039) and HOMA-IR (p = 0.01) were significantly associated with odds of having CAD. The final logistic regression model showed that age, sex, HOMA-IR, and MAP were the most important determinants of having CAD. There were no significant associations between circulating irisin and NRG4 with odds of having CAD. The final general linear model showed that being men (β = 17.303, 95% CI: 7.086-27.52, P = 0.001), age (Aβ = 0.712, 95% CI: 0.21-1.214, P = 0.006), HOMA-IR (Aβ = 2.168, 95% CI: 0.256 to 4.079, P = 0.027), and NRG4 level (β = 1.836, 95% CI: 0.119-3.553, P = 0.036) were directly associated with higher gensini score. Participants with the three-vessel disease had a mean increase of about 5 units in circulating irisin compared to those with no clinical CAD (β = 5.221, 95% CI: 0.454-9.987, p = 0.032). CONCLUSIONS This study showed that the adipokines NRG4 and Irisin might be associated with the severity of coronary stenosis.
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Affiliation(s)
- Elham Alipoor
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Javad Hosseinzadeh-Attar
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
| | - Ali Vasheghani-Farahani
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Clinical Cardiac Electrophysiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahnaz Salmani
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahsa Rezaei
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Namkhah
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Monireh Ahmadpanahi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Yaser Jenab
- Department of Cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Alidoosti
- Department of Cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Yaseri
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
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13
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Kim YC, Ki SW, Kim H, Kang S, Kim H, Go GW. Recent Advances in Nutraceuticals for the Treatment of Sarcopenic Obesity. Nutrients 2023; 15:3854. [PMID: 37686886 PMCID: PMC10490319 DOI: 10.3390/nu15173854] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 08/26/2023] [Accepted: 09/01/2023] [Indexed: 09/10/2023] Open
Abstract
Sarcopenic obesity, low muscle mass, and high body fat are growing health concerns in the aging population. This review highlights the need for standardized criteria and explores nutraceuticals as potential therapeutic agents. Sarcopenic obesity is associated with insulin resistance, inflammation, hormonal changes, and reduced physical activity. These factors lead to impaired muscle activity, intramuscular fat accumulation, and reduced protein synthesis, resulting in muscle catabolism and increased fat mass. Myostatin and irisin are myokines that regulate muscle synthesis and energy expenditure, respectively. Nutritional supplementation with vitamin D and calcium is recommended for increasing muscle mass and reducing body fat content. Testosterone therapy decreases fat mass and improves muscle strength. Vitamin K, specifically menaquinone-4 (MK-4), improves mitochondrial function and reduces muscle damage. Irisin is a hormone secreted during exercise that enhances oxidative metabolism, prevents insulin resistance and obesity, and improves bone quality. Low-glycemic-index diets and green cardamom are potential methods for managing sarcopenic obesity. In conclusion, along with exercise and dietary support, nutraceuticals, such as vitamin D, calcium, vitamin K, and natural agonists of irisin or testosterone, can serve as promising future therapeutic alternatives.
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Affiliation(s)
| | | | | | | | | | - Gwang-woong Go
- Department of Food and Nutrition, Hanyang University, Seoul 04763, Republic of Korea; (Y.-C.K.); (S.-W.K.); (H.K.); (S.K.); (H.K.)
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14
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Tanveer Y, Saif U, Lim Y. Serum Irisin Levels Are Inversely Correlated With the Severity of Coronary Artery Disease Confirmed by Coronary Angiography: A Comparative Cross-Sectional Study. Cureus 2023; 15:e41475. [PMID: 37546057 PMCID: PMC10404147 DOI: 10.7759/cureus.41475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/06/2023] [Indexed: 08/08/2023] Open
Abstract
Introduction Irisin, a newly discovered myokine, has been reported for its role in coronary artery disease (CAD), which is a major cause of mortality worldwide. Atherosclerosis is the primary cause of CAD. Irisin has been reported to reduce atherosclerosis by improving endothelial function and inhibiting inflammation via iNOS/NF-κB pathways. We sought to investigate the relationship between serum irisin levels and the severity of CAD that is confirmed with coronary angiography. Methods A comparative cross-sectional study was designed between the Chemical Pathology and Cardiology departments at KEMU/Mayo Hospital in Lahore, Pakistan. Patients were divided into group A with mild CAD (<50% stenosis) and group B with moderate-severe CAD (>50% stenosis). Serum was collected from venous blood, and irisin levels were analyzed by ELISA. Inclusion criteria: patients with stable CAD. Exclusion criteria: History of coronary artery bypass grafting (CABG), acute coronary syndrome (ACS), active or chronic infection, hepatic or renal dysfunction. Results The mean + SD age (years) of patients in group B (57.0±9.5) was significantly higher than group A (50.0±13.7). Irisin levels (μg/ml) were significantly higher in group A (15.3±4.6) than in group B (9.3±2.4). Irisin levels were significantly negatively correlated with the severity of CAD (% stenosis). Conclusion Serum irisin levels are low in patients with moderate to severe CAD, and they are negatively correlated with the severity of CAD (% stenosis).
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Affiliation(s)
- Yousaf Tanveer
- Internal Medicine, Craigavon Area Hospital, Northern Ireland, GBR
- Internal Medicine, King Edward Memorial University, Lahore, PAK
| | - Unaizah Saif
- Internal Medicine, King Edward Memorial University, Lahore, PAK
| | - Yizhe Lim
- Internal Medicine, Craigavon Area Hospital, Northern Ireland, GBR
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15
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Tang YL, Tao Y, Zhu L, Shen JL, Cheng H. Role of NLRP3 inflammasome in hepatocellular carcinoma: A double-edged sword. Int Immunopharmacol 2023; 118:110107. [PMID: 37028274 DOI: 10.1016/j.intimp.2023.110107] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/02/2023] [Accepted: 03/24/2023] [Indexed: 04/09/2023]
Abstract
In recent years, the study of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome has become a hot topic, especially its role in various tumors. The incidence of hepatocellular carcinoma is ranked in the top five in China. Hepatocellular carcinoma (HCC) is the predominant and typical form of primary liver cancer. Due to the close relationship between NLRP3 inflammasome and cancers, many studies have investigated its role in HCC. The results suggest that NLRP3 inflammasome participates in both tumor growth inhibition and tumor growth promotion in HCC. Therefore, this review elaborates on the relationship between NLRP3 and HCC and explains its role in HCC. In addition, the potential of NLRP3 as a therapeutic target for cancer therapy is explored, summarizing and classifying impacts of and processes underlying different NLRP3 inflammasome-targeting drugs on HCC.
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Affiliation(s)
- Ying-Le Tang
- Medical College, Yangzhou University, Yangzhou, China; Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China
| | - Yan Tao
- Medical College, Yangzhou University, Yangzhou, China; Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China
| | - Lin Zhu
- Medical College, Yangzhou University, Yangzhou, China; Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China
| | - Jia-Lin Shen
- Medical College, Yangzhou University, Yangzhou, China; Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China
| | - Hong Cheng
- Medical College, Yangzhou University, Yangzhou, China; Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China.
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16
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Wang T, Yu M, Li H, Qin S, Ren W, Ma Y, Bo W, Xi Y, Cai M, Tian Z. FNDC5/Irisin Inhibits the Inflammatory Response and Mediates the Aerobic Exercise-Induced Improvement of Liver Injury after Myocardial Infarction. Int J Mol Sci 2023; 24:ijms24044159. [PMID: 36835571 PMCID: PMC9962088 DOI: 10.3390/ijms24044159] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 02/10/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Myocardial infarction (MI) causes peripheral organ injury, in addition to cardiac dysfunction, including in the liver, which is known as cardiac hepatopathy. Aerobic exercise (AE) can effectively improve liver injury, although the mechanism and targets are currently not well established. Irisin, mainly produced by cleavage of the fibronectin type III domain-containing protein 5 (FNDC5), is a responsible for the beneficial effects of exercise training. In this study, we detected the effect of AE on MI-induced liver injury and explored the role of irisin alongside the benefits of AE. Wildtype and Fndc5 knockout mice were used to establish an MI model and subjected to AE intervention. Primary mouse hepatocytes were treated with lipopolysaccharide (LPS), rhirisin, and a phosphoinositide 3-kinase (PI3K) inhibitor. The results showed that AE significantly promoted M2 polarization of macrophages and improved MI-induced inflammation, upregulated endogenous irisin protein expression and activated the PI3K/ protein kinase B (Akt) signaling pathway in the liver of MI mice, while knockout of Fndc5 attenuated the beneficial effects of AE. Exogenous rhirisin significantly inhibited the LPS-induced inflammatory response, which was attenuated by the PI3K inhibitor. These results suggest that AE could effectively activate the FNDC5/irisin-PI3K/Akt signaling pathway, promote the polarization of M2 macrophages, and inhibit the inflammatory response of the liver after MI.
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Affiliation(s)
- Tao Wang
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi’an 710119, China
| | - Mengyuan Yu
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi’an 710119, China
| | - Hangzhuo Li
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi’an 710119, China
- School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
| | - Shuguang Qin
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi’an 710119, China
| | - Wujing Ren
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi’an 710119, China
| | - Yixuan Ma
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi’an 710119, China
| | - Wenyan Bo
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi’an 710119, China
| | - Yue Xi
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi’an 710119, China
| | - Mengxin Cai
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi’an 710119, China
- Correspondence: (M.C.); (Z.T.)
| | - Zhenjun Tian
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi’an 710119, China
- Correspondence: (M.C.); (Z.T.)
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17
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Salivary irisin level is higher and related with interleukin-6 in generalized periodontitis. Clin Oral Investig 2023:10.1007/s00784-023-04903-9. [PMID: 36763144 DOI: 10.1007/s00784-023-04903-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 02/03/2023] [Indexed: 02/11/2023]
Abstract
OBJECTIVES Irisin plays an important role in energy homeostasis, inflammation, glucose, and lipid metabolism, and it is shown to have relations with many inflammatory diseases. The aim of the study was to determine saliva and serum irisin and IL-6 levels in patients with stage III/grade B periodontitis compared with individuals with healthy periodontium. MATERIALS AND METHODS Twenty patients with stage III grade B periodontitis (P) and 20 periodontally healthy subjects (control; C) were included in this study. Clinical periodontal measurements were recorded. Saliva and serum levels of irisin and interleukin-6 (IL-6) were analyzed by enzyme-linked immunosorbent assay. RESULTS Salivary irisin and IL-6 levels were significantly higher in the periodontitis group (p < 0.001, p = 0.002, respectively). Furthermore, serum IL-6 levels were found significantly higher in the periodontitis group compared with controls (p = 0.011). There was no significant difference between the periodontitis and control for serum irisin levels (p > 0.05). Significant positive correlations were found between all periodontal parameters and salivary irisin and IL-6 (p < 0.05) and also between BMI and saliva and serum IL-6 (respectively; r = 0.530, r = 0.329, p < 0.05). There was a positive correlation between salivary irisin and IL-6 (r = 0.369, p < 0.05). CONCLUSIONS Monitoring of salivary irisin and IL-6 might be potential biomarker for predicting the susceptibility to periodontitis. CLINICAL RELEVANCE Scientific rationale for the study: Irisin is a novel adipomyokine that has played an important role in energy homeostasis, glucose and lipid metabolism, angiogenesis, immunity, and inflammation. Irisin is involved in the pathogenesis of diseases affecting many body systems. IL-6, another adipomyokine, is a major inflammatory mediator and homeostatic regulator of glucose and lipid metabolism and is associated with periodontitis. No studies investigated the relationship between advanced periodontal disease, irisin, and IL-6 together. PRINCIPAL FINDINGS The salivary irisin and IL-6 levels were significantly higher and positively correlated in patients with periodontitis relative to healthy controls. Furthermore, serum IL-6 levels were significantly increased in patients with periodontitis. PRACTICAL IMPLICATIONS The study shows that irisin and IL-6 can be candidate salivary biomarkers for periodontitis and predict to periodontal status.
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Poniedziałek-Czajkowska E, Mierzyński R, Leszczyńska-Gorzelak B. Preeclampsia and Obesity-The Preventive Role of Exercise. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1267. [PMID: 36674022 PMCID: PMC9859423 DOI: 10.3390/ijerph20021267] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 01/05/2023] [Accepted: 01/08/2023] [Indexed: 06/10/2023]
Abstract
Obesity is now recognized as a worldwide epidemic. An inadequate diet and reduced physical activity are acknowledged as the leading causes of excess body weight. Despite growing evidence that obesity is a risk factor for unsuccessful pregnancies, almost half of all women who become pregnant today are overweight or obese. Common complications of pregnancy in this group of women are preeclampsia and gestational hypertension. These conditions are also observed more frequently in women with excessive weight gain during pregnancy. Preeclampsia is one of the most serious pregnancy complications with an unpredictable course, which in its most severe forms, threatens the life and health of the mother and her baby. The early identification of the risk factors for preeclampsia development, including obesity, allows for the implementation of prophylaxis and a reduction in maternal and fetal complications risk. Additionally, preeclampsia and obesity are the recognized risk factors for developing cardiovascular disease in later life, so prophylaxis and treating obesity are paramount for their prevention. Thus, a proper diet and physical activity might play an essential role in the prophylaxis of preeclampsia in this group of women. Limiting weight gain during pregnancy and modifying the metabolic risk factors with regular physical exercise creates favorable metabolic conditions for pregnancy development and benefits the elements of the pathogenetic sequence for preeclampsia development. In addition, it is inexpensive, readily available and, in the absence of contraindications to its performance, safe for the mother and fetus. However, for this form of prevention to be effective, it should be applied early in pregnancy and, for overweight and obese women, proposed as an essential part of planning pregnancy. This paper aims to present the mechanisms of the development of hypertension in pregnancy in obese women and the importance of exercise in its prevention.
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Adropin’s Role in Energy Homeostasis and Metabolic Disorders. Int J Mol Sci 2022; 23:ijms23158318. [PMID: 35955453 PMCID: PMC9369016 DOI: 10.3390/ijms23158318] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 01/27/2023] Open
Abstract
Adropin is a novel 76-amino acid-peptide that is expressed in different tissues and cells including the liver, pancreas, heart and vascular tissues, kidney, milk, serum, plasma and many parts of the brain. Adropin, encoded by the Enho gene, plays a crucial role in energy homeostasis. The literature review indicates that adropin alleviates the degree of insulin resistance by reducing endogenous hepatic glucose production. Adropin improves glucose metabolism by enhancing glucose utilization in mice, including the sensitization of insulin signaling pathways such as Akt phosphorylation and the activation of the glucose transporter 4 receptor. Several studies have also demonstrated that adropin improves cardiac function, cardiac efficiency and coronary blood flow in mice. Adropin can also reduce the levels of serum triglycerides, total cholesterol and low-density lipoprotein cholesterol. In contrast, it increases the level of high-density lipoprotein cholesterol, often referred to as the beneficial cholesterol. Adropin inhibits inflammation by reducing the tissue level of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6. The protective effect of adropin on the vascular endothelium is through an increase in the expression of endothelial nitric oxide synthase. This article provides an overview of the existing literature about the role of adropin in different pathological conditions.
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20
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Dimberg J, Shamoun L, Landerholm K, Wågsäter D. Effects of diabetes type 2 and metformin treatment in Swedish patients with colorectal cancer. World J Gastroenterol 2022; 28:2148-2151. [PMID: 35664033 PMCID: PMC9134133 DOI: 10.3748/wjg.v28.i19.2148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/01/2022] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
The association between type 2 diabetes mellitus (DM) and colorectal cancer (CRC) has been thoroughly investigated and reports have demonstrated that the risk of CRC is increased in DM patients. The association between DM and the survival of patients with CRC is controversial. Evidence suggests that metformin with its anti-inflammatory effects is a protective factor against the development of CRC among DM patients and that metformin therapy is associated with a better prognosis in patients with DM. In our cohort, we did not find any associations between the presence of DM or metformin and cancer specific survival or any relation to plasma levels of a panel of 40 inflammatory factors and irisin. On the other hand, we identified that the insulin-like growth factor binding protein 7 single nucleotide polymorphism rs2041437 was associated with DM in CRC patients. The dominance of the T bearing genotypes in patients with DM was statistically significant (P = 0.038), with an odds ratio of 1.66 (95% confidence interval: 1.03-2.69).
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Affiliation(s)
- Jan Dimberg
- Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, Jönköping 551 11, Sweden
| | - Levar Shamoun
- Department of Laboratory Medicine and Pathology, Region Jönköping County, Jönköping 553 05, Sweden
- Department of Medical Cell Biology, Uppsala University, Uppsala 751 23, Sweden
| | - Kalle Landerholm
- Department of Surgery, Region Jönköping County, Jönköping 553 05, Sweden
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping 581 85, Sweden
| | - Dick Wågsäter
- Department of Medical Cell Biology, Uppsala University, Uppsala 751 23, Sweden
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Peng J, Wu J. Effects of the FNDC5/Irisin on Elderly Dementia and Cognitive Impairment. Front Aging Neurosci 2022; 14:863901. [PMID: 35431908 PMCID: PMC9009536 DOI: 10.3389/fnagi.2022.863901] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/01/2022] [Indexed: 11/20/2022] Open
Abstract
Population aging is an inevitable problem nowadays, and the elderly are going through a lot of geriatric symptoms, especially cognitive impairment. Irisin, an exercise-stimulating cleaved product from transmembrane fibronectin type III domain-containing protein 5 (FNDC5), has been linked with favorable effects on many metabolic diseases. Recently, mounting studies also highlighted the neuroprotective effects of irisin on dementia. The current evidence remains uncertain, and few clinical trials have been undertaken to limit its clinical practice. Therefore, we provided an overview of current scientific knowledge focusing on the preventive mechanisms of irisin on senile cognitive decline and dementia, in terms of the possible connections between irisin and neurogenesis, neuroinflammation, oxidative stress, and dementia-related diseases. This study summarized the recent advances and ongoing studies, aiming to provide a better scope into the effectiveness of irisin on dementia progression, as well as a mediator of muscle brain cross talk to provide theoretical support for exercise therapy for patients with dementia. Whether irisin is a diagnostic or prognostic factor for dementia needs more researches.
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22
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Myokines and Resistance Training: A Narrative Review. Int J Mol Sci 2022; 23:ijms23073501. [PMID: 35408868 PMCID: PMC8998961 DOI: 10.3390/ijms23073501] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/18/2022] [Accepted: 03/21/2022] [Indexed: 01/27/2023] Open
Abstract
In the last few years, the muscular system has gained attention due to the discovery of the muscle-secretome and its high potency for retaining or regaining health. These cytokines, described as myokines, released by the working muscle, are involved in anti-inflammatory, metabolic and immunological processes. These are able to influence human health in a positive way and are a target of research in metabolic diseases, cancer, neurological diseases, and other non-communicable diseases. Therefore, different types of exercise training were investigated in the last few years to find associations between exercise, myokines and their effects on human health. Particularly, resistance training turned out to be a powerful stimulus to enhance myokine release. As there are different types of resistance training, different myokines are stimulated, depending on the mode of training. This narrative review gives an overview about resistance training and how it can be utilized to stimulate myokine production in order to gain a certain health effect. Finally, the question of why resistance training is an important key regulator in human health will be discussed.
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Xie F, Zou T, Chen J, Liang P, Wang Z, You J. Polysaccharides from Enteromorpha prolifera improves insulin sensitivity and promotes adipose thermogenesis in diet-induced obese mice associated with activation of PGC-1α-FNDC5/irisin pathway. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.104994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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Altaş M, Uca AU, Akdağ T, Odabaş FÖ, Tokgöz OS. Serum levels of irisin and nesfatin-1 in multiple sclerosis. ARQUIVOS DE NEURO-PSIQUIATRIA 2022; 80:161-167. [PMID: 35195223 DOI: 10.1590/0004-282x-anp-2020-0520] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 02/01/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune chronic neurological disease. Currently, there are no effective serum biomarkers to verify MS diagnosis, to assess disease prognosis, and evaluate response to MS treatment. OBJECTIVE The present study is a preliminary assessment of irisin and nesfatin-1 serum levels in patients with relapsing- remitting MS (RRMS). METHODS A total of 86 participants, 42 patients with RRMS diagnosis and 44 healthy controls were included in the study. The serum irisin and nesfatin-1 parameters of the patients and control group members were analyzed. RESULTS Irisin and nesfatin-1 levels of the RRMS patients were significantly lower than the controls (z: -3.82, p<0.001; z: -4.79, p<0.001, respectively) The cut-off level of irisin is 10.390 (ng/mL) (sensitivity: 84.1%, specificity: 71.4%, AUC: 0.800), and the cut-off level of nestatin-1 is 7.155 (ng/mL) (sensitivity: 68.2%, specificity: 64.3%, AUC: 0.739) in the ROC analysis. For these cut-off levels in the case-control groups, the lower irisin and nesfatin-1 levels are the independent variables for MS patients (OR 9.723, 95%CI 2.884-32.785, p<0.001; OR 3.992, 95%CI 1.336-11.928, p<0.001) respectively. CONCLUSION The present study revealed lower irisin and nesfatin-1 levels in patients with RRMS. These findings suggest that the decreased levels of irisin and nesfatin-1 peptides may contribute to MS pathogenesis such as inflammation, oxidative stress, and apoptosis in MS, leading to demyelination, axonal damage with neuronal loss, and gliosis.
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Affiliation(s)
- Mustafa Altaş
- Necmettin Erbakan University, Meram Faculty of Medicine, Department of Neurology, Konya, Turkey
| | - Ali Ulvi Uca
- Necmettin Erbakan University, Meram Faculty of Medicine, Department of Neurology, Konya, Turkey
| | - Turan Akdağ
- Necmettin Erbakan University, Meram Vocational School, Konya, Turkey
| | - Faruk Ömer Odabaş
- University of Health Sciences, Konya City Hospital, Department of Neurology, Konya, Turkey
| | - Osman Serhat Tokgöz
- Necmettin Erbakan University, Meram Faculty of Medicine, Department of Neurology, Konya, Turkey
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Gamez-Nava JI, Ramirez-Villafaña M, Cons-Molina F, Gomez-Ramirez EE, Esparza-Guerrero Y, Saldaña-Cruz AM, Sanchez-Rodriguez EN, Jacobo-Cuevas H, Totsuka-Sutto SE, Perez-Guerrero EE, Huerta M, Trujillo X, Vasquez-Jimenez JC, Nava-Zavala AH, Cardona-Muñoz EG, Alcaraz-Lopez MF, Gonzalez-Lopez L. Serum irisin concentrations and osteoporotic vertebral fractures in women with rheumatoid arthritis: A cross-sectional study. Medicine (Baltimore) 2022; 101:e28799. [PMID: 35147113 PMCID: PMC8830829 DOI: 10.1097/md.0000000000028799] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 01/15/2022] [Indexed: 12/26/2022] Open
Abstract
Irisin stimulates osteoblast differentiation increasing bone mass a decreasing in irisin levels might contribute to osteoporotic fractures in inflammatory diseases. To date, there is controverted whether irisin levels are associated with osteoporotic fractures in rheumatoid arthritis (RA). Therefore, we evaluate the association of serum irisin with osteoporotic Vertebral Fractures (VFs) in women with RA.A total of 148 women with RA was included in the study.Clinical characteristics and risk factors of VFs was evaluated. For measurement of bone mineral density we included the assessment of lumbar spine (AP L1-L4) and Femoral Neck by dual-energy X-ray absorptiometry (DXA). VFs were evaluated by lateral vertebral assessment (LVA) of the dorsal and lumbar regions using X-ray and digital vertebral morphometry by DXA, using the Genant scale. Serum irisin levels were measured by ELISA. A reference group of 97 women with non-rheumatic diseases were included to compare irisin levels.RA patients had a median age of 59 years and 41% had osteoporosis. Seventy three (49%) had VFs. Lower irisin levels were observed in RA patients compared to controls (94 ± 74 vs 135 ± 103, P < .001). Irisin concentrations were lower in RA + VFs than RA non-VFs (74 ± 42 vs 113 ± 92 ng/mL, P = .001). In the multivariable logistic regression analysis the low 50 percentile irisin levels < 73 ng/mL (OR:3.1, 95% CI:1.55-6.2, P = .001), and disease duration of RA (OR:1.04, 95% CI:1.001-1.08, P = .04) were associated with an increase in the risk of VFs.A decrease of irisin levels is associated to VFs in RA. These results are valuable to consider that RA patients with low levels of irisin are in a potential risk of VFs.
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Affiliation(s)
- Jorge Ivan Gamez-Nava
- Departamento de Fisiología, Instituto de Investigación en Ciencias Biomédicas, Programa de Doctorado en Salud Publica, Departamento de Salud Publica, Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
- Unidad de Investigación Biomédica 02, UMAE, Hospital de Especialidades, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
| | - Melissa Ramirez-Villafaña
- Unidad de Investigación Biomédica 02, UMAE, Hospital de Especialidades, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
- Programa de Doctorado en Ciencias Médicas, Universidad de Colima, Colima, Colima, México
| | - Fidencio Cons-Molina
- Centro de Investigación en Artritis y Osteoporosis, Mexicali , Baja California, México
| | - Eli Efrain Gomez-Ramirez
- Departamento de Fisiología, Instituto de Investigación en Ciencias Biomédicas, Programa de Doctorado en Salud Publica, Departamento de Salud Publica, Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| | - Yussef Esparza-Guerrero
- Departamento de Fisiología, Instituto de Investigación en Ciencias Biomédicas, Programa de Doctorado en Salud Publica, Departamento de Salud Publica, Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| | - Ana Miriam Saldaña-Cruz
- Departamento de Fisiología, Instituto de Investigación en Ciencias Biomédicas, Programa de Doctorado en Salud Publica, Departamento de Salud Publica, Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| | - Esther Nerida Sanchez-Rodriguez
- Departamento de Fisiología, Instituto de Investigación en Ciencias Biomédicas, Programa de Doctorado en Salud Publica, Departamento de Salud Publica, Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| | - Heriberto Jacobo-Cuevas
- Departamento de Fisiología, Instituto de Investigación en Ciencias Biomédicas, Programa de Doctorado en Salud Publica, Departamento de Salud Publica, Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| | - Sylvia Elena Totsuka-Sutto
- Departamento de Fisiología, Instituto de Investigación en Ciencias Biomédicas, Programa de Doctorado en Salud Publica, Departamento de Salud Publica, Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| | - Edsaul Emilio Perez-Guerrero
- Departamento de Fisiología, Instituto de Investigación en Ciencias Biomédicas, Programa de Doctorado en Salud Publica, Departamento de Salud Publica, Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| | - Miguel Huerta
- Centro Universitario de Investigaciones Biomédicas (CUIB), Universidad de Colima, Colima, México
| | - Xochitl Trujillo
- Centro Universitario de Investigaciones Biomédicas (CUIB), Universidad de Colima, Colima, México
| | | | - Arnulfo Hernan Nava-Zavala
- Unidad de Investigación Biomédica 02, UMAE, Hospital de Especialidades, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
- Programa Internacional de Medicina, Universidad Autónoma de Guadalajara, Zapopan, Jalisco, México
| | - Ernesto German Cardona-Muñoz
- Departamento de Fisiología, Instituto de Investigación en Ciencias Biomédicas, Programa de Doctorado en Salud Publica, Departamento de Salud Publica, Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
| | - Miriam Fabiola Alcaraz-Lopez
- Departamento de Medicina Interna-Reumatología, Hospital General Regional 46 and Hospital General Regional 110; IMSS, Guadalajara, Jalisco, México
| | - Laura Gonzalez-Lopez
- Departamento de Fisiología, Instituto de Investigación en Ciencias Biomédicas, Programa de Doctorado en Salud Publica, Departamento de Salud Publica, Programa de Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México
- Departamento de Medicina Interna-Reumatología, Hospital General Regional 46 and Hospital General Regional 110; IMSS, Guadalajara, Jalisco, México
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Tuğgüm S, Bozkir Ç, Aslan S, Yilmaz A, Çelikkol A. Evaluation of vaspin and irisin hormones levels in diabetic rats and relationship with diet. MEDITERRANEAN JOURNAL OF NUTRITION AND METABOLISM 2022. [DOI: 10.3233/mnm-211586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND: Type-2 diabetes with an increasing prevalence is a public health problem. Irisin and vaspin, which are secreted a majority from adipose tissue, are discovered hormones recently, and their effects on diabetes are studied. OBJECTIVE: This study aims to the effects of diet on these hormones levels in diabetic rats. METHODS: In this study, ten-week-old 18 Wistar-Albino rats were divided into three groups randomly. The diabetic group (n = 6) was fed a high-fat diet (HFD). Other rats were divided into two control groups, one of them (n = 6) was fed a control diet (CD), and the other group (n = 6) was fed HFD. The feeding time for all groups was 4 weeks. Streptozotocin (STZ) was used for diabetes induction in rats. RESULTS: At the end of the four weeks, the body weight of the diabetic group decreased significantly. In the diabetic group compared to the control groups, it was observed that besides high fasting blood glucose (FBG), triglyceride, total cholesterol levels, and insulin resistance (HOMA-IR) scores. Vaspin levels were significantly higher in diabetic rats, while irisin levels were similar between groups. Besides, vaspin level correlation with biochemical parameters such as glucose, triglycerides, total cholesterol, and HOMA-IR score was significant. CONCLUSION: In conclusion, this study showed that besides the evidence that vaspine is a hormone associated with diabetes, diet composition could give an opinion about the type-2 diabetes process by looking at hormone levels.
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Affiliation(s)
- Sergen Tuğgüm
- Tekirdağ Namık Kemal University, School of Health, Department of Nutrition and Dietetics, Tekirdağ/Turkey
| | - Çiğdem Bozkir
- Inonu University, Faculty of Health Sciences, Department of Nutrition an Dietetics, Malatya/Turkey
| | - Serkan Aslan
- Tekirdağ Namık Kemal University, School of Health, Department of Nutrition and Dietetics, Tekirdağ/Turkey
| | - Ahsen Yilmaz
- Tekirdağ Namık Kemal University, Faculty of Medicine, Department of Medical Biochemistry, Tekirdağ/Turkey
| | - Aliye Çelikkol
- Tekirdağ Namık Kemal University, Faculty of Medicine, Department of Medical Biochemistry, Tekirdağ/Turkey
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Bilski J, Pierzchalski P, Szczepanik M, Bonior J, Zoladz JA. Multifactorial Mechanism of Sarcopenia and Sarcopenic Obesity. Role of Physical Exercise, Microbiota and Myokines. Cells 2022; 11:cells11010160. [PMID: 35011721 PMCID: PMC8750433 DOI: 10.3390/cells11010160] [Citation(s) in RCA: 105] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/27/2021] [Accepted: 12/31/2021] [Indexed: 02/07/2023] Open
Abstract
Obesity and ageing place a tremendous strain on the global healthcare system. Age-related sarcopenia is characterized by decreased muscular strength, decreased muscle quantity, quality, and decreased functional performance. Sarcopenic obesity (SO) is a condition that combines sarcopenia and obesity and has a substantial influence on the older adults’ health. Because of the complicated pathophysiology, there are disagreements and challenges in identifying and diagnosing SO. Recently, it has become clear that dysbiosis may play a role in the onset and progression of sarcopenia and SO. Skeletal muscle secretes myokines during contraction, which play an important role in controlling muscle growth, function, and metabolic balance. Myokine dysfunction can cause and aggravate obesity, sarcopenia, and SO. The only ways to prevent and slow the progression of sarcopenia, particularly sarcopenic obesity, are physical activity and correct nutritional support. While exercise cannot completely prevent sarcopenia and age-related loss in muscular function, it can certainly delay development and slow down the rate of sarcopenia. The purpose of this review was to discuss potential pathways to muscle deterioration in obese individuals. We also want to present the current understanding of the role of various factors, including microbiota and myokines, in the process of sarcopenia and SO.
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Affiliation(s)
- Jan Bilski
- Department of Biomechanics and Kinesiology, Chair of Biomedical Sciences, Faculty of Health Sciences, Institute of Physiotherapy, Jagiellonian University Medical College, 31-008 Krakow, Poland
- Correspondence: ; Tel.: +48-12-421-93-51
| | - Piotr Pierzchalski
- Department of Medical Physiology, Chair of Biomedical Sciences, Faculty of Health Sciences, Institute of Physiotherapy, Jagiellonian University Medical College, 31-126 Krakow, Poland; (P.P.); (J.B.)
| | - Marian Szczepanik
- Department of Medical Biology, Chair of Biomedical Sciences, Faculty of Health Sciences, Institute of Physiotherapy, Jagiellonian University Medical College, 31-034 Krakow, Poland;
| | - Joanna Bonior
- Department of Medical Physiology, Chair of Biomedical Sciences, Faculty of Health Sciences, Institute of Physiotherapy, Jagiellonian University Medical College, 31-126 Krakow, Poland; (P.P.); (J.B.)
| | - Jerzy A. Zoladz
- Chair of Exercise Physiology and Muscle Bioenergetics, Faculty of Health Sciences, Jagiellonian University Medical College, 31-066 Krakow, Poland;
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Demirel S, Sahinturk S, Isbil N, Ozyener F. Physiological role of K + channels in irisin-induced vasodilation in rat thoracic aorta. Peptides 2022; 147:170685. [PMID: 34748790 DOI: 10.1016/j.peptides.2021.170685] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/01/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022]
Abstract
Irisin, an exercise-induced myokine, has been shown to have a peripheral vasodilator effect. However, little is known about the mechanisms underlying its effects. In this study, it was aimed to investigate the vasoactive effects of irisin on rat thoracic aorta, and the hypothesis that voltage-gated potassium (KV) channels, ATP-sensitive potassium (KATP) channels, small-conductance calcium-activated potassium (SKCa) channels, large-conductance calcium-activated potassium (BKCa) channels, intermediate-conductance calcium-activated potassium (IKCa) channels, inward rectifier potassium (Kir) channels, and two-pore domain potassium (K2P) channels may have roles in these effects. Isometric contraction-relaxation responses of isolated thoracic aorta rings were measured with an organ bath model. The steady contraction was induced with both 10-5 M phenylephrine and 45 mM KCl, and then the concentration-dependent responses of irisin (10-9-10-6 M) were examined. Irisin exerted the vasorelaxant effects in both endothelium-intact and -denuded aortic rings at concentrations of 10-8, 10-7, and 10-6 M (p < 0.001). Besides, KV channel blocker 4-aminopyridine, KATP channel blocker glibenclamide, SKCa channel blocker apamin, BKCa channel blockers tetraethylammonium and iberiotoxin, IKCa channel blocker TRAM-34, and Kir channel blocker barium chloride incubations significantly inhibited the irisin-induced relaxation responses. However, incubation of K2P TASK-1 channel blocker anandamide did not cause a significant decrease in the relaxation responses of irisin. In conclusion, the first physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. Furthermore, this study is the first to report that irisin-induced relaxation responses are associated with the activity of KV, KATP, SKCa, BKCa, IKCa, and Kir channels.
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Affiliation(s)
- Sadettin Demirel
- Department of Physiology, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey.
| | - Serdar Sahinturk
- Department of Physiology, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey.
| | - Naciye Isbil
- Department of Physiology, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey.
| | - Fadil Ozyener
- Department of Physiology, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey.
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Liu H, Wang M, Jin Z, Sun D, Zhu T, Liu X, Tan X, Shi G. FNDC5 induces M2 macrophage polarization and promotes hepatocellular carcinoma cell growth by affecting the PPARγ/NF-κB/NLRP3 pathway. Biochem Biophys Res Commun 2021; 582:77-85. [PMID: 34695754 DOI: 10.1016/j.bbrc.2021.10.041] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 10/18/2021] [Indexed: 01/15/2023]
Abstract
PURPOSE The purpose of this study was to investigate the effect of FNDC5 expression levels in hepatocellular carcinoma on the phenotypic changes of macrophages in tumor tissues. METHODS In this study, we established an in vitro co-culture system of hepatocellular carcinoma cells and macrophages. Then we performed overexpression or knockdown of FNDC5 gene in hepatocellular carcinoma cells to observe the effect of changes in FNDC5 expression level on the phenotypic changes of THP-1 macrophages. And the conclusions obtained in the in vitro assay were further validated by a subcutaneous tumorigenic nude mice model. RESULTS Our findings suggest that elevated FNDC5 expression in hepatocellular carcinoma cells lead to an increased M2 phenotype and decreased M1 phenotype in macrophages. This effect may be achieved by elevating PPARγ levels in macrophages while decreasing NF-κB and NLRP3 levels. These changes could be reversed by using PPARγ inhibitors. CONCLUSION We preliminarily demonstrated that FNDC5 in hepatocellular carcinoma cells promotes the polarization of M2 macrophages by affecting the PPARγ/NF-κB/NLRP3 pathway.
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Affiliation(s)
- Huayuan Liu
- Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, China
| | - Mengya Wang
- Department of Physiology, School of Basic Medicine, Qingdao University, China
| | - Zhipeng Jin
- Graduate School of Dalian Medical University, China
| | - Dongxu Sun
- Graduate School of Dalian Medical University, China
| | - Ting Zhu
- Department of Gynecology, The Affiliated Qingdao Municipal Hospital of Qingdao University, China
| | - Xinyue Liu
- Graduate School of Dalian Medical University, China
| | - Xueying Tan
- Department of Laboratory, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China.
| | - Guangjun Shi
- Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, China.
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Shaw A, Tóth BB, Király R, Arianti R, Csomós I, Póliska S, Vámos A, Korponay-Szabó IR, Bacso Z, Győry F, Fésüs L, Kristóf E. Irisin Stimulates the Release of CXCL1 From Differentiating Human Subcutaneous and Deep-Neck Derived Adipocytes via Upregulation of NFκB Pathway. Front Cell Dev Biol 2021; 9:737872. [PMID: 34708041 PMCID: PMC8542801 DOI: 10.3389/fcell.2021.737872] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 09/15/2021] [Indexed: 12/19/2022] Open
Abstract
Thermogenic brown and beige adipocytes might open up new strategies in combating obesity. Recent studies in rodents and humans have indicated that these adipocytes release cytokines, termed "batokines". Irisin was discovered as a polypeptide regulator of beige adipocytes released by myocytes, primarily during exercise. We performed global RNA sequencing on adipocytes derived from human subcutaneous and deep-neck precursors, which were differentiated in the presence or absence of irisin. Irisin did not exert an effect on the expression of characteristic thermogenic genes, while upregulated genes belonging to various cytokine signaling pathways. Out of the several upregulated cytokines, CXCL1, the highest upregulated, was released throughout the entire differentiation period, and predominantly by differentiated adipocytes. Deep-neck area tissue biopsies also showed a significant release of CXCL1 during 24 h irisin treatment. Gene expression data indicated upregulation of the NFκB pathway upon irisin treatment, which was validated by an increase of p50 and decrease of IκBα protein level, respectively. Continuous blocking of the NFκB pathway, using a cell permeable inhibitor of NFκB nuclear translocation, significantly reduced CXCL1 release. The released CXCL1 exerted a positive effect on the adhesion of endothelial cells. Together, our findings demonstrate that irisin stimulates the release of a novel adipokine, CXCL1, via upregulation of NFκB pathway in neck area derived adipocytes, which might play an important role in improving tissue vascularization.
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Affiliation(s)
- Abhirup Shaw
- Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.,Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen, Hungary
| | - Beáta B Tóth
- Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Róbert Király
- Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Rini Arianti
- Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.,Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen, Hungary
| | - István Csomós
- Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Szilárd Póliska
- Genomic Medicine and Bioinformatics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Attila Vámos
- Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.,Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen, Hungary
| | - Ilma R Korponay-Szabó
- Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zsolt Bacso
- Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.,Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary
| | - Ferenc Győry
- Department of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - László Fésüs
- Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Endre Kristóf
- Laboratory of Cell Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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Huangfu LX, Cai XT, Yang JN, Wang HC, Li YX, Dai ZF, Yang RL, Lin XH. Irisin attenuates inflammation in a mouse model of ulcerative colitis by altering the intestinal microbiota. Exp Ther Med 2021; 22:1433. [PMID: 34707714 PMCID: PMC8543469 DOI: 10.3892/etm.2021.10868] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 05/13/2020] [Indexed: 12/16/2022] Open
Abstract
Evidence has demonstrated that the gut microbiota, which consists of probiotics and pathogenic microorganisms, is involved in the initiation of ulcerative colitis (UC) via the dysregulation of intestinal microflora and normal immune interactions, which ultimately leads to intestinal mucosal dysfunction. Irisin is released from muscle cells and displays anti-inflammatory effects; however, the mechanisms underlying irisin-mediated anti-inflammatory effects in UC have not been previously reported. In the present study, mice were divided into the following four groups: i) Control; ii) irisin; iii) dextran sulfate sodium (DSS) salt; and iv) DSS + irisin. Subsequently, the effects of irisin were investigated by observing alterations in intestinal microbes. Irisin significantly reduced the degree of inflammation in UC by reversing alterations to the macroscopic score, histological score, number of CD64+ cells and inflammatory cytokine alterations (P<0.05). Analysis of the microbial diversity in the stools of mice with active UC indicated that the five bacteria that displayed the greatest alterations in relative abundance were Alloprevotella, Bacteroides, Lachnospiraceae-UCG-001, Prebotellaceae-UCG-001 and Rikenellaceae-RCB-gut-group. Furthermore, Bactoroides were positively correlated with the histopathological score (P=0.001; R=0.977) and interleukin (IL)-23 levels (P=0.008; R=0.924). Alloprevotella (P=0.001; R=-0.943), Lachnospiraceae-UCG-001 (P=0.000; R=-0.973) and Rikenollaceae-RC8-gut-group (P=0.001; R=-0.971) were negatively correlated with the histopathological score. Furthermore, Lachnospiraceae-UCG-001 (P=0.01; R=-0.873) and Rikenollaceae-RC8-gut-group (P=0.049; R=-0.814) were negatively correlated with IL-23 levels. In summary, the results of the present study suggested that irisin improved inflammation in a UC mouse model potentially via altering the gut microbiota.
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Affiliation(s)
- Lu Xin Huangfu
- Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China.,Department of Geriatrics, Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China
| | - Xin Tong Cai
- Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Jing Nan Yang
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Hui Chao Wang
- Department of Nephrology, The First Affiliated Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Yu Xia Li
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Zhi Feng Dai
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Rui Lin Yang
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Xu Hong Lin
- Department of Clinical Laboratory, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
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Long-Term Effect of Exercise on Irisin Blood Levels-Systematic Review and Meta-Analysis. Healthcare (Basel) 2021; 9:healthcare9111438. [PMID: 34828485 PMCID: PMC8618299 DOI: 10.3390/healthcare9111438] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/21/2021] [Accepted: 10/22/2021] [Indexed: 12/30/2022] Open
Abstract
Physical exercise may activate a number of important biochemical processes in the human body. The aim of this systematic review and meta-analysis was to identify the long-term effect of physical activity on irisin blood levels. We searched PubMed, Scopus, and Web of Science for articles addressing the long-term effect of physical exercise on irisin blood levels. Fifty-nine articles were included in the final qualitative and quantitative syntheses. A statistically significant within-group effect of exercise on irisin blood levels was in 33 studies; out of them, the irisin level increased 23× and decreased 10×. The significant positive between-groups effect was found 11×. Furthermore, the meta-analysis indicated that physical exercise had a significant positive effect on irisin blood levels (SMD = 0.39 (95% CI 0.27–0.52)). Nevertheless, considerably high heterogeneity was found in all the analyses. This systematic review and meta-analysis indicate that physical exercise might increase irisin blood levels; however, the results of individual studies were considerably inconsistent, which questions the methodological detection of irisin by ELISA kits.
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Cheng ZB, Huang L, Xiao X, Sun JX, Zou ZK, Jiang JF, Lu C, Zhang HY, Zhang C. Irisin in atherosclerosis. Clin Chim Acta 2021; 522:158-166. [PMID: 34425103 DOI: 10.1016/j.cca.2021.08.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 08/14/2021] [Accepted: 08/18/2021] [Indexed: 12/11/2022]
Abstract
Irisin, a novel exercise-induced myokine, has been shown to play important roles in increasing white adipose tissue browning, regulating energy metabolism and improving insulin resistance. Growing evidence suggests a direct role for irisin in preventing atherosclerosis (AS) by inhibiting oxidative stress, improving dyslipidemia, facilitating anti-inflammation, reducing cellular damage and recovering endothelial function. In addition, some studies have noted that serum irisin levels play an essential role in cardiovascular diseases (CVDs) risk prediction, highlighting that irisin has the potential to be a useful predictive marker and therapeutic target of AS, especially in monitoring therapeutic efficacy. This review summarizes the understanding of irisin-mediated regulation in essential biological pathways and functions in atherosclerosis and prompts further exploitation of the biological properties of irisin in the pathogenesis of atherosclerosis.
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Affiliation(s)
- Zhe-Bin Cheng
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Research Laboratory of Translational Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Departments of Stomatology, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China
| | - Liang Huang
- Research Laboratory of Translational Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China
| | - Xuan Xiao
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410013, People's Republic of China
| | - Jia-Xiang Sun
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Research Laboratory of Translational Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Departments of Clinical Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China
| | - Zi-Kai Zou
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Research Laboratory of Translational Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Departments of Clinical Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China
| | - Jie-Feng Jiang
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Research Laboratory of Translational Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Departments of Clinical Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China
| | - Cong Lu
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Research Laboratory of Translational Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Departments of Clinical Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China
| | - Hai-Ya Zhang
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Research Laboratory of Translational Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China; Departments of Clinical Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China
| | - Chi Zhang
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China.
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Kazeminasab F, Marandi SM, Baharlooie M, Safaeinejad Z, Nasr-Esfahani MH, Ghaedi K. Aerobic exercise modulates noncoding RNA network upstream of FNDC5 in the Gastrocnemius muscle of high-fat-diet-induced obese mice. J Physiol Biochem 2021; 77:589-600. [PMID: 34405363 DOI: 10.1007/s13105-021-00825-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 07/01/2021] [Indexed: 11/26/2022]
Abstract
The purpose of the study was to determine the influence of aerobic exercise with a fat-rich diet on ncRNAs expression associated with FNDC5 in the Gastrocnemius muscle of the obese mice. Twenty-five male mice were grouped into two categories of normal diet (ND) and high-fat diet (HF) treatments for three months. For the subsequent treatment, HF-fed animals (obese) were proceeded in four groups: HF-Trained (n = 5), HF-Untrained (n = 5), ND-Trained (n = 5), and ND-Untrained (n = 5). Simultaneously, ND fed mice (n = 5) continued receiving normal diet and being untrained. In the training group, exercise was applied using a treadmill for 2 months. The Gastrocnemius muscle was excised for the assessment of FNDC5 mRNA, protein levels, and ncRNAs. Using bioinformatics tools, two potential miRNAs, miR-129-5p and miR-140-5p, and four lncRNAs constructing a network with FNDC5 were identified. Significant decrease was observed in both miR-129-5p and miR-140-5p in the HF-fed mice vs. ND-fed mice (p < 0.01). Significant increase of lncRNAs Meg3, Malat1, Neat1, and Kcnq1ot1 correlating in the network was also detected (p < 0.001 for all lncRNAs) in HF-fed mice and trained mice (p < 0.001 for Neat1, Meg3, and Kcnq1ot1). The present study suggests that an increase in the muscle FNDC5 of the high-fat diet mice is governed by an expression regulation of suggested ncRNAs, which were revealed by bioinformatics study to be involved in the insulin resistance and glucose homeostasis pathways.
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Affiliation(s)
- Fatemeh Kazeminasab
- Department of Physical Education and Sport Sciences, Faculty of Human Sciences, University of Kashan, Kashan, Iran , University of Kashan , Kashan , Iran.
| | - Sayed Mohammad Marandi
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran , University of Isfahan , Isfahan , Iran.
| | - Maryam Baharlooie
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Zahra Safaeinejad
- Department of Animal Biotechnology, Cell Sciences Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Mohammad Hossein Nasr-Esfahani
- Department of Animal Biotechnology, Cell Sciences Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
| | - Kamran Ghaedi
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
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Chen Y, Ding J, Zhao Y, Ju S, Mao H, Peng XG. Irisin induces white adipose tissue browning in mice as assessed by magnetic resonance imaging. Exp Biol Med (Maywood) 2021; 246:1597-1606. [PMID: 33882700 PMCID: PMC8326442 DOI: 10.1177/15353702211006049] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 03/09/2021] [Indexed: 11/16/2022] Open
Abstract
This study aimed to track and evaluate the effect of low-dose irisin on the browning of white adipose tissue (WAT) in mice using magnetic resonance imaging (MRI) noninvasively in vivo. Mature white adipocytes extracted from mice were cultured, induced and characterized before being treated by irisin. The volume and fat fraction of WAT were quantified using MRI in normal chow diet and high fat mice after injection of irisin. The browning of cultured white adipocytes and WAT in mice were validated by immunohistochemistry and western blotting for uncoupling protein 1 (UCP1) and deiodinase type II (DIO2). The serum indexes were examined with high fat diet after irisin intervention. UCP1 and DIO2 in adipocytes showed increases responding to the irisin treatment. The size of white adipocytes in mice receiving irisin intervention was reduced. MRI measured volumes and fat fraction of WAT were significantly lower after Irisin treatment. Blood glucose and cholesterol levels were reduced in high fat diet mice after irisin treatment. Irisin intervention exerted browning of WAT, resulting reduction of volume and fat fraction of WAT as measured by MRI. Furthermore, it improved the condition of mice with diet-induced obesity and related metabolic disorders.
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Affiliation(s)
- Yue Chen
- Jiangsu Key Laboratory of Molecular and Functional Imaging,
Department of Radiology, Zhongda Hospital, Medical School, Southeast University,
Nanjing 210009, P. R. China
| | - Jie Ding
- Jiangsu Key Laboratory of Molecular and Functional Imaging,
Department of Radiology, Zhongda Hospital, Medical School, Southeast University,
Nanjing 210009, P. R. China
| | - Yufei Zhao
- Jiangsu Key Laboratory of Molecular and Functional Imaging,
Department of Radiology, Zhongda Hospital, Medical School, Southeast University,
Nanjing 210009, P. R. China
| | - Shenghong Ju
- Jiangsu Key Laboratory of Molecular and Functional Imaging,
Department of Radiology, Zhongda Hospital, Medical School, Southeast University,
Nanjing 210009, P. R. China
| | - Hui Mao
- Department of Radiology and Imaging Sciences, Emory University,
Atlanta, GA 30322-1007, USA
| | - Xin-Gui Peng
- Jiangsu Key Laboratory of Molecular and Functional Imaging,
Department of Radiology, Zhongda Hospital, Medical School, Southeast University,
Nanjing 210009, P. R. China
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Li H, Qin S, Liang Q, Xi Y, Bo W, Cai M, Tian Z. Exercise Training Enhances Myocardial Mitophagy and Improves Cardiac Function via Irisin/FNDC5-PINK1/Parkin Pathway in MI Mice. Biomedicines 2021; 9:biomedicines9060701. [PMID: 34205641 PMCID: PMC8234442 DOI: 10.3390/biomedicines9060701] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 06/15/2021] [Accepted: 06/18/2021] [Indexed: 12/16/2022] Open
Abstract
Myocardial infarction is the major cause of death in cardiovascular disease. In vitro and in vivo models are used to find the exercise mode which has the most significant effect on myocardial irisin/FNDC5 expression and illuminate the cardioprotective role and mechanisms of exercise-activated myocardial irisin/FNDC5-PINK1/Parkin-mediated mitophagy in myocardial infarction. The results indicated that expression of irisin/FNDC5 in myocardium could be up-regulated by different types of exercise and skeletal muscle electrical stimulation, which then promotes mitophagy and improves cardiac function and the effect of resistance exercise. Resistance exercise can improve cardiac function by activating the irisin/FNDC5-PINK1/Parkin-LC3/P62 pathway, regulating mitophagy and inhibiting oxidative stress. OPA1 may play an important role in the improvement of cardiac function and mitophagy pathway in myocardial infarction mice by irisin-mediated resistance exercise. Resistance exercise is expected to become an effective therapeutic way to promote myocardial infarction rehabilitation.
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Leustean L, Preda C, Teodoriu L, Mihalache L, Arhire L, Ungureanu MC. Role of Irisin in Endocrine and Metabolic Disorders—Possible New Therapeutic Agent? APPLIED SCIENCES 2021; 11:5579. [DOI: 10.3390/app11125579] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Irisin is a novel hormone that provides a possible solution for the treatment of metabolic disorders. Discovered in 2012 by Boström et al., irisin very quickly became an interesting subject in medical research. Irisin has been found in cerebrospinal fluid, the cerebellum, thyroid, pineal gland, liver, pancreas, testis, spleen, adult stomach, and human fetuses. Regarding the actions of irisin, both in animals and humans, the results are contradictory but interesting. Its capability to influence adipose tissue and glycemic homeostasis may be utilized in order to treat hypothyroidism, polycystic ovary syndrome, Prader–Willi syndrome, and other endocrine and metabolic disorders. Considering its osteogenic potential, irisin might be a therapeutic choice in diseases caused by a sedentary lifestyle. New data indicate that irisin treatment may serve in the treatment of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection. Furthermore, several therapeutic agents, such as insulin, metformin, fenofibrate, exenatide, and melatonin, influence the concentrations of irisin in animal models or in humans. Nutritional factors including polyunsaturated fatty acids may also have an effect on irisin concentrations. While it may be “too good to be true,” irisin offers many opportunities for future research that would aim to find its optimal therapeutical role in endocrine and metabolic diseases.
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Affiliation(s)
- Letitia Leustean
- Endocrinology Department, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700111 Iasi, Romania
| | - Cristina Preda
- Endocrinology Department, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700111 Iasi, Romania
| | - Laura Teodoriu
- Endocrinology Department, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700111 Iasi, Romania
| | - Laura Mihalache
- Diabetes and Metabolic Disorders Department, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700111 Iasi, Romania
| | - Lidia Arhire
- Diabetes and Metabolic Disorders Department, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700111 Iasi, Romania
| | - Maria-Christina Ungureanu
- Endocrinology Department, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700111 Iasi, Romania
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ANGPTL3 Variants Associate with Lower Levels of Irisin and C-Peptide in a Cohort of Arab Individuals. Genes (Basel) 2021; 12:genes12050755. [PMID: 34067751 PMCID: PMC8170900 DOI: 10.3390/genes12050755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 05/11/2021] [Accepted: 05/12/2021] [Indexed: 11/16/2022] Open
Abstract
ANGPTL3 is an important regulator of lipid metabolism. Its inhibition in people with hypercholesteremia reduces plasma lipid levels dramatically. Genome-wide association studies have associated ANGPTL3 variants with lipid traits. Irisin, an exercise-modulated protein, has been associated with lipid metabolism. Intracellular accumulation of lipids impairs insulin action and contributes to metabolic disorders. In this study, we evaluate the impact of ANGPTL3 variants on levels of irisin and markers associated with lipid metabolism and insulin resistance. ANGPTL3 rs1748197 and rs12130333 variants were genotyped in a cohort of 278 Arab individuals from Kuwait. Levels of irisin and other metabolic markers were measured by ELISA. Significance of association signals was assessed using Bonferroni-corrected p-values and empirical p-values. The study variants were significantly associated with low levels of c-peptide and irisin. Levels of c-peptide and irisin were mediated by interaction between carrier genotypes (GA + AA) at rs1748197 and measures of IL13 and TG, respectively. While levels of c-peptide and IL13 were directly correlated in individuals with the reference genotype, they were inversely correlated in individuals with the carrier genotype. Irisin correlated positively with TG and was strong in individuals with carrier genotypes. These observations illustrate ANGPTL3 as a potential link connecting lipid metabolism, insulin resistance and cardioprotection.
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Zou T, Li S, Wang B, Wang Z, Liu Y, You J. Curcumin improves insulin sensitivity and increases energy expenditure in high-fat-diet-induced obese mice associated with activation of FNDC5/irisin. Nutrition 2021; 90:111263. [PMID: 33975064 DOI: 10.1016/j.nut.2021.111263] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 03/21/2021] [Accepted: 03/29/2021] [Indexed: 01/14/2023]
Abstract
OBJECTIVE Curcumin (Cur) has a beneficial role in preventing metabolic dysfunctions; however, the underlying mechanism are not yet fully understood. The aim of this study was to evaluate whether the beneficial metabolic effects of curcumin are associated with the regulation of energy metabolism and activation of fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin. METHODS We used cellular and molecular techniques to investigate the effects of Cur on C57 BL/6 mice that were fed either a control diet or a high-fat diet (HFD) with or without 0.2% Cur for 10 wk. Factors involved in energy metabolism, inflammatory responses, and insulin signaling, as well as the involvement of FNDC5/irisin pathway, were assessed. RESULTS Cur alleviated adiposity and suppressed inflammatory response in white adipose tissue (WAT) of HFD mice. Meanwhile, Cur administration increased plasma irisin concentration and improved insulin sensitivity of HFD mice. Cur increased the oxygen consumption and heat production and reduced respiratory exchange ratio (RES) in HFD mice, which were accompanied by the enhancement of metabolic activity in brown fat and inguinal WAT. Additionally, the improvement of basal metabolic rate by Cur may be partly regulated by the FNDC5/ p38 mitogen-activated protein kinase (p38 MAPK)/extracellular signal-related kinase (ERK) 1/2 pathway. CONCLUSIONS These findings demonstrated that dietary Cur alleviated diet-induced adiposity by improving insulin sensitivity and whole body energy metabolism via the FNDC5/p38 MAPK/ERK pathways.
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Affiliation(s)
- Tiande Zou
- Jiangxi Province Key Laboratory of Animal Nutrition, Jiangxi Agricultural University, Jiangxi, China
| | - Shuo Li
- Jiangxi Province Key Laboratory of Animal Nutrition, Jiangxi Agricultural University, Jiangxi, China
| | - Bo Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Zirui Wang
- Jiangxi Province Key Laboratory of Animal Nutrition, Jiangxi Agricultural University, Jiangxi, China
| | - Yue Liu
- Jiangxi Province Key Laboratory of Animal Nutrition, Jiangxi Agricultural University, Jiangxi, China
| | - Jinming You
- Jiangxi Province Key Laboratory of Animal Nutrition, Jiangxi Agricultural University, Jiangxi, China.
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Li H, Wang F, Yang M, Sun J, Zhao Y, Tang D. The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity. Int J Endocrinol 2021; 2021:6572342. [PMID: 33790964 PMCID: PMC7997758 DOI: 10.1155/2021/6572342] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 01/05/2021] [Accepted: 03/03/2021] [Indexed: 12/13/2022] Open
Abstract
Obesity is a worldwide health problem due to the imbalance of energy intake and energy expenditure. Irisin, a newly identified exercise-responsive myokine, which is produced by the proteolytic cleavage of fibronectin type III domain-containing protein 5 (FNDC5), has emerged as a promising therapeutic strategy to combat obesity and obesity-related complications. Various studies in mice have shown that irisin could respond to systematic exercise training and promote white-to-brown fat transdifferentiation, but the role and function of irisin in humans are controversial. In this review, we systematically introduced and analyzed the factors that may contribute to these inconsistent results. Furthermore, we also described the potential anti-inflammatory properties of irisin under a variety of inflammatory conditions. Finally, the review discussed the existing unresolved issues and controversies about irisin, including the transcription of the irisin precursor FNDC5 gene in humans, the cleavage site of the yet unknown proteolytic enzyme that cleaves irisin from FNDC5, and the reliability of irisin levels measured with available detection methods.
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Affiliation(s)
- Hui Li
- Center for Gene and Immunotherapy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
| | - Fang Wang
- Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
| | - Mu Yang
- Center for Gene and Immunotherapy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
| | - Jiao Sun
- Center for Gene and Immunotherapy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
| | - Yi Zhao
- Center for Gene and Immunotherapy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
| | - Dongqi Tang
- Center for Gene and Immunotherapy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
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Pignataro P, Dicarlo M, Zerlotin R, Zecca C, Dell’Abate MT, Buccoliero C, Logroscino G, Colucci S, Grano M. FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective. Int J Mol Sci 2021; 22:ijms22041605. [PMID: 33562601 PMCID: PMC7915567 DOI: 10.3390/ijms22041605] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/01/2021] [Accepted: 02/02/2021] [Indexed: 02/07/2023] Open
Abstract
Irisin, the circulating peptide originating from fibronectin type III domain-containing protein 5 (FNDC5), is mainly expressed by muscle fibers under peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) control during exercise. In addition to several beneficial effects on health, physical activity positively affects nervous system functioning, particularly the hippocampus, resulting in amelioration of cognition impairments. Recently, FNDC5/irisin detection in hippocampal neurons and the presence of irisin in the cerebrospinal fluid opened a new intriguing chapter in irisin history. Interestingly, in the hippocampus of mice, exercise increases FNDC5 levels and upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF, displaying neuroprotection and anti-inflammatory effects, is mainly produced by microglia and astrocytes. In this review, we discuss how these glial cells can morphologically and functionally switch during neuroinflammation by modulating the expression of a plethora of neuroprotective or neurotoxic factors. We also focus on studies investigating the irisin role in neurodegenerative diseases (ND). The emerging involvement of irisin as a mediator of the multiple positive effects of exercise on the brain needs further studies to better deepen this issue and the potential use in therapeutic approaches for neuroinflammation and ND.
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Affiliation(s)
- Patrizia Pignataro
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, 70124 Bari, Italy; (P.P.); (M.D.); (G.L.); (S.C.)
- Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy; (R.Z.); (C.B.)
| | - Manuela Dicarlo
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, 70124 Bari, Italy; (P.P.); (M.D.); (G.L.); (S.C.)
| | - Roberta Zerlotin
- Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy; (R.Z.); (C.B.)
| | - Chiara Zecca
- Center for Neurodegenerative Diseases and the Aging Brain, Department of Clinical Research in Neurology, University of Bari, “Pia Fondazione Card G. Panico” Hospital Tricase, 73039 Lecce, Italy; (C.Z.); (M.T.D.)
| | - Maria Teresa Dell’Abate
- Center for Neurodegenerative Diseases and the Aging Brain, Department of Clinical Research in Neurology, University of Bari, “Pia Fondazione Card G. Panico” Hospital Tricase, 73039 Lecce, Italy; (C.Z.); (M.T.D.)
| | - Cinzia Buccoliero
- Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy; (R.Z.); (C.B.)
| | - Giancarlo Logroscino
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, 70124 Bari, Italy; (P.P.); (M.D.); (G.L.); (S.C.)
- Center for Neurodegenerative Diseases and the Aging Brain, Department of Clinical Research in Neurology, University of Bari, “Pia Fondazione Card G. Panico” Hospital Tricase, 73039 Lecce, Italy; (C.Z.); (M.T.D.)
| | - Silvia Colucci
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, 70124 Bari, Italy; (P.P.); (M.D.); (G.L.); (S.C.)
| | - Maria Grano
- Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy; (R.Z.); (C.B.)
- Correspondence: ; Tel.: +39-080-5478-361
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Berezin AE, Berezin AA, Lichtenauer M. Myokines and Heart Failure: Challenging Role in Adverse Cardiac Remodeling, Myopathy, and Clinical Outcomes. DISEASE MARKERS 2021; 2021:6644631. [PMID: 33520013 PMCID: PMC7819753 DOI: 10.1155/2021/6644631] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/08/2020] [Accepted: 01/06/2021] [Indexed: 12/13/2022]
Abstract
Heart failure (HF) is a global medical problem that characterizes poor prognosis and high economic burden for the health system and family of the HF patients. Although modern treatment approaches have significantly decreased a risk of the occurrence of HF among patients having predominant coronary artery disease, hypertension, and myocarditis, the mortality of known HF continues to be unacceptably high. One of the most important symptoms of HF that negatively influences tolerance to physical exercise, well-being, social adaptation, and quality of life is deep fatigue due to HF-related myopathy. Myopathy in HF is associated with weakness of the skeletal muscles, loss of myofibers, and the development of fibrosis due to microvascular inflammation, metabolic disorders, and mitochondrial dysfunction. The pivotal role in the regulation of myocardial and skeletal muscle rejuvenation, attenuation of muscle metabolic homeostasis, and protection against ischemia injury and apoptosis belongs to myokines. Myokines are defined as a wide spectrum of active molecules that are directly synthesized and released by both cardiac and skeletal muscle myocytes and regulate energy homeostasis in autocrine/paracrine manner. In addition, myokines have a large spectrum of pleiotropic capabilities that are involved in the pathogenesis of HF including cardiac remodeling, muscle atrophy, and cardiac cachexia. The aim of the narrative review is to summarize the knowledge with respect to the role of myokines in adverse cardiac remodeling, myopathy, and clinical outcomes among HF patients. Some myokines, such as myostatin, irisin, brain-derived neurotrophic factor, interleukin-15, fibroblast growth factor-21, and growth differential factor-11, being engaged in the regulation of the pathogenesis of HF-related myopathy, can be detected in peripheral blood, and the evaluation of their circulating levels can provide new insights to the course of HF and stratify patients at higher risk of poor outcomes prior to sarcopenic stage.
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Affiliation(s)
- Alexander E. Berezin
- Internal Medicine Department, State Medical University, Ministry of Health of Ukraine, Zaporozhye 69035, Ukraine
| | - Alexander A. Berezin
- Internal Medicine Department, Medical Academy of Post-Graduate Education, Ministry of Health of Ukraine, Zaporozhye 69096, Ukraine
| | - Michael Lichtenauer
- Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
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Pervin S, Reddy ST, Singh R. Novel Roles of Follistatin/Myostatin in Transforming Growth Factor-β Signaling and Adipose Browning: Potential for Therapeutic Intervention in Obesity Related Metabolic Disorders. Front Endocrinol (Lausanne) 2021; 12:653179. [PMID: 33897620 PMCID: PMC8062757 DOI: 10.3389/fendo.2021.653179] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 03/19/2021] [Indexed: 12/12/2022] Open
Abstract
Obesity is a global health problem and a major risk factor for several metabolic conditions including dyslipidemia, diabetes, insulin resistance and cardiovascular diseases. Obesity develops from chronic imbalance between energy intake and energy expenditure. Stimulation of cellular energy burning process has the potential to dissipate excess calories in the form of heat via the activation of uncoupling protein-1 (UCP1) in white and brown adipose tissues. Recent studies have shown that activation of transforming growth factor-β (TGF-β) signaling pathway significantly contributes to the development of obesity, and blockade or inhibition is reported to protect from obesity by promoting white adipose browning and increasing mitochondrial biogenesis. Identification of novel compounds that activate beige/brown adipose characteristics to burn surplus calories and reduce excess storage of fat are actively sought in the fight against obesity. In this review, we present recent developments in our understanding of key modulators of TGF-β signaling pathways including follistatin (FST) and myostatin (MST) in regulating adipose browning and brown adipose mass and activity. While MST is a key ligand for TGF-β family, FST can bind and regulate biological activity of several TGF-β superfamily members including activins, bone morphogenic proteins (BMP) and inhibins. Here, we review the literature supporting the critical roles for FST, MST and other proteins in modulating TGF-β signaling to influence beige and brown adipose characteristics. We further review the potential therapeutic utility of FST for the treatment of obesity and related metabolic disorders.
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Affiliation(s)
- Shehla Pervin
- Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, United States
- Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Science, Los Angeles, CA, United States
| | - Srinivasa T. Reddy
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
- Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
| | - Rajan Singh
- Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, United States
- Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Science, Los Angeles, CA, United States
- Department of Endocrinology, Men’s Health: Aging and Metabolism, Brigham and Women’s Hospital, Boston, MA, United States
- *Correspondence: Rajan Singh,
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Zhu X, Li X, Wang X, Chen T, Tao F, Liu C, Tu Q, Shen G, Chen JJ. Irisin deficiency disturbs bone metabolism. J Cell Physiol 2021; 236:664-676. [PMID: 32572964 PMCID: PMC7722136 DOI: 10.1002/jcp.29894] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 05/26/2020] [Accepted: 06/12/2020] [Indexed: 12/20/2022]
Abstract
Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone-like peptide. Recent studies have reported the involvement of irisin in many physiological and pathological conditions with bone mineral density changes, including osteopenia and osteoporotic fractures. In this study, we generated the first line of Osx-Cre:FNDC5/irisin KO mice, in which FNDC5/irisin was specifically deleted in the osteoblast lineage. Gene and protein expressions of irisin were remarkably decreased in bones but no significant differences in other tissues were observed in knockout mice. FNDC5/irisin deficient mice showed a lower bone density and significantly delayed bone development and mineralization from early-stage to adulthood. Our phenotypical analysis exhibited decreased osteoblast-related gene expression and increased osteoclast-related gene expression in bone tissues, and reduced adipose tissue browning due to bone-born irisin deletion. By harvesting and culturing MSCs from the knockout mice, we found that osteoblastogenesis was inhibited and osteoclastogenesis was increased. By using irisin stimulated wildtype primary cells as a gain-of-function model, we further revealed the effects and mechanisms of irisin on promoting osteogenesis and inhibiting osteoclastogenesis in vitro. In addition, positive effects of exercise, including bone strength enhancement and body weight loss were remarkably weakened due to irisin deficiency. Interestingly, these changes can be rescued by supplemental administration of recombinant irisin during exercise. Our study indicates that irisin plays an important role in bone metabolism and the crosstalk between bone and adipose tissue. Irisin represents a potential molecule for the prevention and treatment of bone metabolic diseases.
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Affiliation(s)
- Xiaofang Zhu
- Department of Oral & Cranio‐Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
- Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts
| | - Xiangfen Li
- Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts
| | - Xiaoxuan Wang
- Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts
| | - Ting Chen
- Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts
| | - Fengjuan Tao
- Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts
| | - Chuanju Liu
- Department of Orthopedics Surgery and Department of Cell Biology, New York University School of Medicine, New York, New York
| | - Qisheng Tu
- Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts
| | - Guofang Shen
- Department of Oral & Cranio‐Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Jake J. Chen
- Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts
- Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts
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Miyamoto A, Asai K, Kadotani H, Maruyama N, Kubo H, Okamoto A, Sato K, Yamada K, Ijiri N, Watanabe T, Kawaguchi T. Ninjin'yoeito Ameliorates Skeletal Muscle Complications in COPD Model Mice by Upregulating Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Expression. Int J Chron Obstruct Pulmon Dis 2020; 15:3063-3077. [PMID: 33273811 PMCID: PMC7708308 DOI: 10.2147/copd.s280401] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 11/09/2020] [Indexed: 12/19/2022] Open
Abstract
Purpose Sarcopenia, the loss of skeletal muscle mass and strength, is a common systemic consequence of chronic obstructive pulmonary disease (COPD) and is correlated with higher mortality. Ninjin’yoeito (NYT) is a Japanese herbal medicine used to treat athrepsia and anorexia and is reported to ameliorate weight loss and muscular dysfunction. Recent studies have shown that its crude components upregulate the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-related pathway, which is involved in skeletal muscle functions. Here, we examined whether NYT improves skeletal muscle complications by upregulating PGC-1α in COPD model mice. Materials and Methods Mice were divided into four groups: control, NYT, smoking, and smoking + NYT. The smoking and smoking + NYT groups were exposed to cigarette smoke for 60 min once daily. The mice in the NYT and smoking + NYT groups were fed an NYT-containing diet (3% w/w). We performed cellular analysis of bronchoalveolar lavage fluid, assessed pulmonary morphological changes, examined the expression of PGC-1α mRNA and protein in the gastrocnemius and soleus muscle, measured the hindlimb muscle volume with micro-computed tomography, and determined the myofiber proportion in soleus muscle after 12 weeks. Results Cigarette smoke exposure resulted in reduced skeletal muscle volume and slow-twitch muscle fibers and development of pulmonary emphysema. NYT feeding induced partial recovery of the damaged alveolar wall; however, NYT did not ameliorate smoke-induced alveolar enlargement. These findings revealed that NYT did not have sufficient efficacy in suppressing pulmonary emphysema. On the other hand, PGC-1α expression in muscle tissue of the NYT-fed mice increased significantly, resulting in suppression of smoke-induced loss of muscle mass and alteration in the muscle fiber distribution. Conclusion NYT increases PGC-1α expression in the muscle of COPD model mice and is involved in suppressing cigarette smoke-induced muscle complications. NYT may be a novel preventive and therapeutic medication for muscular dysfunctions in COPD.
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Affiliation(s)
- Atsushi Miyamoto
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
| | - Kazuhisa Asai
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
| | - Hideaki Kadotani
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
| | - Naomi Maruyama
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
| | - Hiroaki Kubo
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
| | - Atsuko Okamoto
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
| | - Kanako Sato
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
| | - Kazuhiro Yamada
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
| | - Naoki Ijiri
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
| | - Tetsuya Watanabe
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
| | - Tomoya Kawaguchi
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka-City, Osaka, Japan
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Irandoost P, Mesri Alamdari N, Saidpour A, Shidfar F, Roshanravan N, Asghari Jafarabadi M, Farsi F, Asghari Hanjani N, Vafa M. The effects of royal jelly and tocotrienol-rich fraction on impaired glycemic control and inflammation through irisin in obese rats. J Food Biochem 2020; 44:e13493. [PMID: 33020956 DOI: 10.1111/jfbc.13493] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 08/15/2020] [Accepted: 09/03/2020] [Indexed: 12/16/2022]
Abstract
The effects of royal jelly (RJ) and tocotrienol-rich fraction (TRF) on obesity-induced glucose intolerance and inflammation were assessed in the current study. Regarding irisin as an important adipomyokine that attenuates obesity-induced disorders, we evaluated whether RJ and TRF could exert their metabolism regulatory effects through irisin. Obese rats were fed a high-fat diet (HFD) with or without supplementation of RJ, TRF, or both, for 8 weeks. At the end of the intervention, weight, irisin, glycemic, and inflammatory indices were measured. The weight of the rats did not remarkably reduce in any of the groups. Glucose homeostasis and inflammation were improved when we added RJ and TRF to HFD. RJ elevated irisin concentration, but the effect of TRF on irisin was not noticeable. Our results indicated that, despite the lack of significant weight loss, RJ and TRF promoted healthy obesity. This improvement was mediated by irisin in RJ consuming rats. PRACTICAL APPLICATIONS: Obesity is a public health concern associated with several chronic disorders. The beneficial effects of irisin on obesity-related disorders are well-established. It is the first study assessing the effect of RJ and TRF as functional foods, with pharmacological and nutritional activities on obesity complications, through irisin mediation. Our study demonstrated that RJ exerts its metabolic regulatory effects by irisin as a mediator. Our investigation makes a remarkable contribution to the literature, because it suggests a new mechanism for the anti-obesity properties of RJ and TRF.
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Affiliation(s)
- Pardis Irandoost
- Student Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Naimeh Mesri Alamdari
- Student Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Atoosa Saidpour
- National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzad Shidfar
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Neda Roshanravan
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Asghari Jafarabadi
- Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farnaz Farsi
- Student Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Nazanin Asghari Hanjani
- Student Research Committee, Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Vafa
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
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Kirat D, Hamada M, Moustafa A, Miyasho T. Irisin/FNDC5: A participant in camel metabolism. Saudi J Biol Sci 2020; 28:693-706. [PMID: 33424357 PMCID: PMC7783842 DOI: 10.1016/j.sjbs.2020.10.061] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 10/26/2020] [Accepted: 10/27/2020] [Indexed: 12/31/2022] Open
Abstract
The quantification, localization, production, function, and regulation of irisin/FNDC5 in camel species have not been previously studied. The objective of this study was to detect the irisin content in Arabian camel blood and tissues and study the gene expression of FNDC5 and PGC-1α in camel skeletal muscles and white adipose tissue depots under basal conditions. To monitor if exercise influences blood and tissue irisin protein levels as well as FNDC5 and PGC-1α gene expression levels, we analyzed irisin concentrations in the serum, skeletal muscles (soleus and gastrocnemius), and white adipose tissues (hump, subcutaneous, visceral, epididymal, and perirenal) in both control (n = 6) and exercised group (n = 6) using ELISA and determined the cellular localization of irisin/FNDC5 and the mRNA levels of FNDC5 and PGC-1α in skeletal muscles and adipose tissues via immunohistochemistry and real-time PCR, respectively. The possible regulatory roles of exercise on some hormones and metabolites as well as the detection of links between serum irisin and other circulating hormones (insulin, leptin, and cortisol) and metabolites (glucose, free fatty acids, triglycerides, and ATP) were explored for the first time in camels. Our results indicated that exercise induces tissue-specific regulation of the camel irisin, FNDC5, and PGC-1α levels, which subsequently regulates the circulating irisin level. Significant associations were detected between the levels of irisin/FNDC5/PGC-1α in camels and the metabolic and hormonal responses to exercise. Our study suggested that irisin regulates, or is regulated by, glucose, FFA, insulin, leptin, and cortisol in camels. The novel results of the present study will serve as baseline data for camels.
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Affiliation(s)
- Doaa Kirat
- Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Mohamed Hamada
- Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Amira Moustafa
- Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Taku Miyasho
- Laboratory of Animal Biological Responses, Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan
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Micielska K, Kortas JA, Gmiat A, Jaworska J, Kozlowska M, Lysak-Radomska A, Rodziewicz-Flis E, Zychowska M, Ziemann E. Habitually inactive physically - a proposed procedure of counteracting cognitive decline in women with diminished insulin sensitivity through a high-intensity circuit training program. Physiol Behav 2020; 229:113235. [PMID: 33130034 DOI: 10.1016/j.physbeh.2020.113235] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 10/02/2020] [Accepted: 10/20/2020] [Indexed: 12/30/2022]
Abstract
This study verified the impact of five weeks of high-intensity circuit training (HICT) on changes in concentration of exerkines in relation to cognitive functions. Sedentary women (n = 33; age=39±13 years) were randomly assigned into the HICT (n = 21) group or the control group (n = 12). The HICT group performed 15 training sessions; meanwhile, the control group performed the HICT twice, only at baseline and at the end of the experiment. Blood samples were collected before, 1 h and 24 h after the first and last HICT, to evaluate the concentration of exerkines: brain-derived neurotrophic factor (BDNF), irisin, fibroblast growth factor-21 (FGF-21), interleukin-6 (IL-6) and cathepsin B (CATB) using enzyme immunoassay method. Cognitive functions and quality of life were assessed using the Vienna Test System and the Short Form Health Survey. HICT induced improvement of cognitive function and quality of life, and these changes were accompanied by an increase of BDNF and shifts in CATB concentration. HICT program caused a decrease in FGF-21 concentration, which was modified by age and insulin sensitivity. The improvement of cognitive functions was more pronounced in females, who experienced a drop in FGF-21. In summary, HICT program, that can be performed during pandemic, enhanced cognitive functions and this response was related to changes in exerkines.
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Affiliation(s)
- Katarzyna Micielska
- Department of Physical Education and Lifelong Sports, Poznan University of Physical Education, Poznan 61-871, Poland; Department of Anatomy and Anthropology, Gdansk University of Physical Education and Sport, Gdansk 80-336, Poland
| | - Jakub Antoni Kortas
- Department of Sport, Gdansk University of Physical Education and Sport, Gdansk 80-336, Poland
| | - Anna Gmiat
- Department of Physiology, Gdansk University of Physical Education and Sport, Gdansk 80-336, Poland
| | - Joanna Jaworska
- Department of Physical Education and Lifelong Sports, Poznan University of Physical Education, Poznan 61-871, Poland
| | - Marta Kozlowska
- Department of Physiology, Gdansk University of Physical Education and Sport, Gdansk 80-336, Poland
| | - Anna Lysak-Radomska
- Department of Occupation Therapy, Gdansk University of Physical Education and Sport, Gdansk 80-336, Poland
| | - Ewa Rodziewicz-Flis
- Department of Physiotherapy, Gdansk University of Physical Education and Sport, Gdansk 80-336, Poland
| | - Malgorzata Zychowska
- Institute of Physical Education, Department of Sport, Kazimierz Wielki University in Bydgoszcz, Bydgoszcz 85-064, Poland
| | - Ewa Ziemann
- Department of Athletics, Strength and Conditioning, Poznan University of Physical Education, Poznan 61-871, Poland.
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Shan D, Zou L, Liu X, Cai Y, Dong R, Hu Y. Circulating Irisin Level and Thyroid Dysfunction: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2182735. [PMID: 33195690 PMCID: PMC7641689 DOI: 10.1155/2020/2182735] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 10/12/2020] [Accepted: 10/14/2020] [Indexed: 02/05/2023]
Abstract
Both thyroid hormones and irisin have profound influences on the metabolism of the human body. Based on their similarities, several studies have been conducted to explore changes in irisin levels in patients with hypothyroidism and hyperthyroidism. This study was conducted in accordance with the PRISMA statement and the MOOSE reporting guideline. Based on a preregistered protocol (PROSPERO-CRD42019138430), a comprehensive search of eight databases was performed from inception to April 2020. Studies with original data collected from patients with thyroid dysfunction were included. Subgroup analysis was performed based on the different types of clinical manifestations and patient characteristics. The quality of each study and the presence of publication bias were assessed by the Newcastle-Ottawa score (NOS) and funnel plot with Egger's test, respectively. A total of 11 studies with 1210 participants were included. Ten studies were identified as high-quality studies. Pooled analysis indicated decreased irisin levels in patients with hypothyroidism (MD -10.37, 95% CI -17.81 to -2.93). Subgroup analysis revealed an even lower level of irisin in patients with clinical-type hypothyroidism (MD -17.03, 95% CI -30.58 to -3.49) and hypothyroidism caused by autoimmune disease (MD -19.38, 95% CI -36.50 to -2.26). No differences were found after achieving euthyroid status from levothyroxine treatment in patients with hypothyroidism compared with controls. No differences were found between patients with hyperthyroidism and controls. Correlation analyses revealed a possible negative correlation between irisin and TSH and positive correlations between irisin and both fT3 and fT4. Irisin was correlated with TSH receptor antibodies.
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Affiliation(s)
- Dan Shan
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610041, China
| | - Li Zou
- Department of Paediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Xijiao Liu
- Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yitong Cai
- West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - Ruihong Dong
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610041, China
| | - Yayi Hu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610041, China
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50
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Zhao M, Zhou X, Yuan C, Li R, Ma Y, Tang X. Association between serum irisin concentrations and sarcopenia in patients with liver cirrhosis: a cross-sectional study. Sci Rep 2020; 10:16093. [PMID: 32999391 PMCID: PMC7527993 DOI: 10.1038/s41598-020-73176-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 09/10/2020] [Indexed: 02/07/2023] Open
Abstract
Sarcopenia is an independent predictor of mortality in patients with liver cirrhosis. However, evidence has emerged that skeletal muscles mediate their protective effect against sarcopenia by secreting myokines. Therefore, we investigated whether irisin was associated with sarcopenia in patients with liver cirrhosis. This was an observational cross-sectional study of data collected from 187 cirrhotic patients. Sarcopenia was defined by computed tomography (CT) scans using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L3 SMI). Morning irisin levels were obtained in all patients. Of the 187 patients, sarcopenia was noted in 73 (39%). Irisin concentrations were lower in sarcopenic patients (32.40 pg/ml [interquartile range (IQR): 18.70, 121.26], p < 0.001) than in nonsarcopenic patients. There was a weak correlation between L3 SMI and irisin levels (r = 0.516, p < 0.001). Multivariable regression analysis including L3 SMI, body mass index (BMI), very-low-density lipoprotein (VLDL)-cholesterol, aspartate aminotransferase (AST), adiponectin, and irisin levels showed that L3 SMI (odds ratio [OR] = 0.915, p = 0.023), adiponectin levels (OR = 1.074, p = 0.014), irisin levels (OR = 0.993, p < 0.001) and BMI (OR = 0.456, p = 0.004) were independently associated with sarcopenia. Irisin levels are associated with sarcopenia in patients with liver cirrhosis. This paper addresses a gap in the literature and facilitates the future transition into clinical treatment.
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Affiliation(s)
- Mingyuan Zhao
- Department of Internal Medicine, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, 030012, China
| | - Xiaoshuang Zhou
- Department of Internal Medicine, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, 030012, China
| | - Chengying Yuan
- Department of Internal Medicine, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, 030012, China.
| | - Rongshan Li
- Department of Internal Medicine, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, 030012, China
| | - Yuehong Ma
- Department of Internal Medicine, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, 030012, China
| | - Xiaoxian Tang
- Department of Radiology, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, 030012, China
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