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Heo JH, Jeong IK. Journal of Lipid and Atherosclerosis Update 2025. J Lipid Atheroscler 2025; 14:3-4. [PMID: 39911964 PMCID: PMC11791413 DOI: 10.12997/jla.2025.14.1.3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 01/13/2025] [Indexed: 02/07/2025] Open
Affiliation(s)
- Ji Hye Heo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - In-Kyung Jeong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
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Laurindo LF, Laurindo LF, Rodrigues VD, Catharin VMCS, Simili OAG, Barboza GO, Catharin VCS, Sloan KP, Barbalho SM. Unraveling the rationale and conducting a comprehensive assessment of AdipoRon (adiponectin receptor agonist) as a candidate drug for diabetic nephropathy and cardiomyopathy prevention and intervention-a systematic review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:165-177. [PMID: 39136737 DOI: 10.1007/s00210-024-03362-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 08/06/2024] [Indexed: 02/02/2025]
Abstract
Type 2 diabetes mellitus (T2DM) is a widespread chronic disease characterized by persistent hyperglycemia, leading to severe complications such as diabetic cardiomyopathy and nephropathy, significantly affecting patient health and quality of life. The complex mechanisms underlying these complications include chronic inflammation, oxidative stress, and metabolic dysregulation. Diabetic cardiomyopathy, marked by structural and functional heart abnormalities, and diabetic nephropathy, characterized by progressive kidney damage, are major contributors to the increased morbidity and mortality associated with T2DM. AdipoRon, a synthetic adiponectin receptor agonist, has shown potential in preclinical studies for mimicking the beneficial effects of endogenous adiponectin, reducing inflammation and oxidative stress, and improving lipid metabolism and mitochondrial function. This systematic review evaluates the therapeutic potential of AdipoRon, focusing on its impact on diabetic cardiomyopathy and nephropathy. Through a comprehensive literature search and analysis, we highlight AdipoRon's role in ameliorating cardiovascular and renal complications in various animal models and cellular systems. The findings underscore the urgent need for translational clinical studies to validate AdipoRon's efficacy and safety in human populations, aiming to advance this promising therapeutic approach from experimental models to clinical application, potentially offering new hope for improved management of diabetic complications.
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Affiliation(s)
- Lucas Fornari Laurindo
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, São Paulo, Brazil.
- Department of Administration, Associate Degree in Hospital Management, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil.
| | - Lívia Fornari Laurindo
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de São José Do Rio Preto (FAMERP), São José Do Rio Preto 15090-000, São Paulo, Brazil
| | - Victória Dogani Rodrigues
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, São Paulo, Brazil
| | - Virgínia Maria Cavallari Strozze Catharin
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
- School of Medicine, Postgraduate Program in Structural and Functional Interactions in Rehabilitation, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Otávio Augusto Garcia Simili
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Gabriella Oliveira Barboza
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Vitor Cavallari Strozze Catharin
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
- School of Medicine, Postgraduate Program in Structural and Functional Interactions in Rehabilitation, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | | | - Sandra Maria Barbalho
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
- School of Medicine, Postgraduate Program in Structural and Functional Interactions in Rehabilitation, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
- Department of Biochemistry and Nutrition, School of Food and Technology of Marília (FATEC), Marília 17500-000, São Paulo, Brazil
- UNIMAR Charity Hospital, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
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Hemat Jouy S, Mohan S, Scichilone G, Mostafa A, Mahmoud AM. Adipokines in the Crosstalk between Adipose Tissues and Other Organs: Implications in Cardiometabolic Diseases. Biomedicines 2024; 12:2129. [PMID: 39335642 PMCID: PMC11428859 DOI: 10.3390/biomedicines12092129] [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: 08/25/2024] [Revised: 09/14/2024] [Accepted: 09/16/2024] [Indexed: 09/30/2024] Open
Abstract
Adipose tissue was previously regarded as a dormant organ for lipid storage until the identification of adiponectin and leptin in the early 1990s. This revelation unveiled the dynamic endocrine function of adipose tissue, which has expanded further. Adipose tissue has emerged in recent decades as a multifunctional organ that plays a significant role in energy metabolism and homeostasis. Currently, it is evident that adipose tissue primarily performs its function by secreting a diverse array of signaling molecules known as adipokines. Apart from their pivotal function in energy expenditure and metabolism regulation, these adipokines exert significant influence over a multitude of biological processes, including but not limited to inflammation, thermoregulation, immune response, vascular function, and insulin sensitivity. Adipokines are pivotal in regulating numerous biological processes within adipose tissue and facilitating communication between adipose tissue and various organs, including the brain, gut, pancreas, endothelial cells, liver, muscle, and more. Dysregulated adipokines have been implicated in several metabolic diseases, like obesity and diabetes, as well as cardiovascular diseases. In this article, we attempted to describe the significance of adipokines in developing metabolic and cardiovascular diseases and highlight their role in the crosstalk between adipose tissues and other tissues and organs.
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Affiliation(s)
- Shaghayegh Hemat Jouy
- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Central Tehran Branch, Islamic Azad University, Tehran 14778-93855, Iran;
| | - Sukrutha Mohan
- Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA; (S.M.); (G.S.)
| | - Giorgia Scichilone
- Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA; (S.M.); (G.S.)
| | - Amro Mostafa
- Department of Pharmacology, College of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA;
| | - Abeer M. Mahmoud
- Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA; (S.M.); (G.S.)
- Department of Kinesiology and Nutrition, College of Applied Health Sciences, University of Illinois Chicago, Chicago, IL 60612, USA
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Dudakovic A, Limberg AK, Bothun CE, Dilger OB, Bayram B, Bettencourt JW, Salmons HI, Thaler R, Karczewski DC, Owen AR, Iyer VG, Payne AN, Carstens MF, van Wijnen AJ, Berry DJ, Sanchez-Sotelo J, Morrey ME, Abdel MP. AdipoRon reduces TGFβ1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo. J Cell Physiol 2024; 239:e31168. [PMID: 38149794 PMCID: PMC10922972 DOI: 10.1002/jcp.31168] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 11/10/2023] [Accepted: 11/28/2023] [Indexed: 12/28/2023]
Abstract
Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFβ1-mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFβ1-induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA-seq analysis corroborated the anti-myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle-treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.
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Affiliation(s)
- Amel Dudakovic
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
| | - Afton K. Limberg
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Cole E. Bothun
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Oliver B. Dilger
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Banu Bayram
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | | | | | - Roman Thaler
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
| | | | - Aaron R. Owen
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Varun G. Iyer
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Ashley N. Payne
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | | | - Andre J. van Wijnen
- Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT, USA
| | - Daniel J. Berry
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | | | - Mark E. Morrey
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Matthew P. Abdel
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
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Abdalla MMI, Mohanraj J, Somanath SD. Adiponectin as a therapeutic target for diabetic foot ulcer. World J Diabetes 2023; 14:758-782. [PMID: 37383591 PMCID: PMC10294063 DOI: 10.4239/wjd.v14.i6.758] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/25/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
The global burden of diabetic foot ulcers (DFUs) is a significant public health concern, affecting millions of people worldwide. These wounds cause considerable suffering and have a high economic cost. Therefore, there is a need for effective strategies to prevent and treat DFUs. One promising therapeutic approach is the use of adiponectin, a hormone primarily produced and secreted by adipose tissue. Adiponectin has demonstrated anti-inflammatory and anti-atherogenic properties, and researchers have suggested its potential therapeutic applications in the treatment of DFUs. Studies have indicated that adiponectin can inhibit the production of pro-inflammatory cytokines, increase the production of vascular endothelial growth factor, a key mediator of angiogenesis, and inhibit the activation of the intrinsic apoptotic pathway. Additionally, adiponectin has been found to possess antioxidant properties and impact glucose metabolism, the immune system, extracellular matrix remodeling, and nerve function. The objective of this review is to summarize the current state of research on the potential role of adiponectin in the treatment of DFUs and to identify areas where further research is needed in order to fully understand the effects of adiponectin on DFUs and to establish its safety and efficacy as a treatment for DFUs in the clinical setting. This will provide a deeper understanding of the underlying mechanisms of DFUs that can aid in the development of new and more effective treatment strategies.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Physiology, Human Biology Division, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Jaiprakash Mohanraj
- Department of Biochemistry, Human Biology Division, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Sushela Devi Somanath
- Department of Microbiology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
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Kwak S. Are Only p-Values Less Than 0.05 Significant? A p-Value Greater Than 0.05 Is Also Significant! J Lipid Atheroscler 2023; 12:89-95. [PMID: 37265851 PMCID: PMC10232224 DOI: 10.12997/jla.2023.12.2.89] [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: 02/07/2023] [Revised: 03/12/2023] [Accepted: 04/09/2023] [Indexed: 06/03/2023] Open
Abstract
Statistical hypothesis testing compares the significance probability value and the significance level value to determine whether or not to reject the null hypothesis. This concludes "significant or not significant." However, since this process is a process of statistical hypothesis testing, the conclusion of "statistically significant or not statistically significant" is more appropriate than the conclusion of "significant or not significant." Also, in many studies, the significance level is set to 0.05 to compare with the significance probability value, p-value. If the p-value is less than 0.05, it is judged as "significant," and if the p-value is greater than 0.05, it is judged as "not significant." However, since the significance probability is a value set by the researcher according to the circumstances of each study, it does not necessarily have to be 0.05. In a statistical hypothesis test, the conclusion depends on the setting of the significance level value, so the researcher must carefully set the significance level value. In this study, the stages of statistical hypothesis testing were examined in detail, and the exact conclusions accordingly and the contents that should be considered carefully when interpreting them were mentioned with emphasis on statistical hypothesis testing and significance level. In 11 original articles published in the Journal of Lipid and Atherosclerosis in 2022, the interpretation of hypothesis testing and the contents of the described conclusions were reviewed from the perspective of statistical hypothesis testing and significance level, and the content that I would like to be supplemented was mentioned.
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Affiliation(s)
- Sanggyu Kwak
- Department of Medical Statistics, Daegu Catholic University School of Medicine, Daegu, Korea
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Kim YK. Comparing the long non-coding RNA expression profiles of skeletal muscle and kidney tissues from patients with diabetes. PLoS One 2022; 17:e0274794. [PMID: 36155986 PMCID: PMC9512191 DOI: 10.1371/journal.pone.0274794] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 09/03/2022] [Indexed: 11/30/2022] Open
Abstract
Background Diabetes causes the dysregulation of several organs, and these effects are often closely associated with changes in the expression of long non-coding RNAs (lncRNAs), a group of non-coding RNAs, within these tissues. Previous studies have described a variety of changes in the expression profile of several lncRNAs from different organs in response to the pathogenesis of diabetes. However, none of these studies compared the expression profiles of these lncRNAs between these organs. This study was designed to identify common and specific lncRNAs involved in the progression of diabetes in the skeletal muscles and kidneys. Methods Publicly available RNA sequencing data of diabetic patients was obtained from the Gene Expression Omnibus database. By analyzing the expression of lncRNAs in these datasets, differentially expressed lncRNAs in each tissue between non-diabetic and diabetic patients were identified. To identify any lncRNAs changed in common in both kidney and muscle tissues, those lncRNAs that are significantly dysregulated in both datasets were selected. Results These evaluations identified a series of novel lncRNAs unique to each organ and several transcripts that were common to both skeletal muscle and kidney tissues in these patients. Interestingly, the genomic location of these lncRNAs suggests that they reside in close proximity to several protein-coding genes known to be related to diabetes suggesting that these lncRNAs may have a regulatory relationship with their neighboring genes. Conclusion These results offer valuable insights into the role of lncRNAs during the pathogenesis of diabetes.
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Affiliation(s)
- Young-Kook Kim
- Department of Biochemistry, Chonnam National University Medical School, Hwasun, Jeollanam-do, Republic of Korea
- * E-mail:
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