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Orioli L, Thissen JP. Myokines as potential mediators of changes in glucose homeostasis and muscle mass after bariatric surgery. Front Endocrinol (Lausanne) 2025; 16:1554617. [PMID: 40171198 PMCID: PMC11958187 DOI: 10.3389/fendo.2025.1554617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 02/28/2025] [Indexed: 04/03/2025] Open
Abstract
Myokines are bioactive peptides released by skeletal muscle. Myokines exert auto-, para-, or endocrine effects, enabling them to regulate many aspects of metabolism in various tissues. However, the contribution of myokines to the dramatic changes in glucose homeostasis and muscle mass induced by bariatric surgery has not been established. Our review highlights that myokines such as brain-derived neurotrophic factor (BDNF), meteorin-like protein (Metrnl), secreted protein acidic and rich in cysteine (SPARC), apelin (APLN) and myostatin (MSTN) may mediate changes in glucose homeostasis and muscle mass after bariatric surgery. Our review also identifies myonectin as an interesting candidate for future studies, as this myokine may regulate lipid metabolism and muscle mass after bariatric surgery. These myokines may provide novel therapeutic targets and biomarkers for obesity, type 2 diabetes and sarcopenia.
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Affiliation(s)
- Laura Orioli
- Research Laboratory of Endocrinology, Diabetes, and Nutrition, Institute of Experimental and Clinical Research, UCLouvain, Brussels, Belgium
- Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Jean-Paul Thissen
- Research Laboratory of Endocrinology, Diabetes, and Nutrition, Institute of Experimental and Clinical Research, UCLouvain, Brussels, Belgium
- Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Brussels, Belgium
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Zhang Y, Zhao J, Zhou J, Jiang Z, Cheng K, Lei C, Yu L. Apelin-13 attenuates optic nerve damage in glaucomatous mice by regulating glucose metabolism. J Transl Med 2025; 23:200. [PMID: 39966959 PMCID: PMC11837638 DOI: 10.1186/s12967-025-06212-z] [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: 07/17/2024] [Accepted: 02/06/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND In patients with advanced glaucoma, lesions frequently extend beyond the eye and affect other organs. However, early distal consequences of elevated intraocular pressure (IOP) remain unclear. This study aimed to observe glucose uptake in the optic cortex during the early stages of elevated IOP and to investigate the mechanism by which Apelin13 exerts neuroprotective effects. METHODS This study used a single anterior chamber injection of polystyrene microbeads and triblock copolymer hydrogel in 6- to 8-week-old male C57BL/6J mice and observed glucose uptake in the optic cortex during the initial phase of IOP elevation using micro-positron emission tomography/magnetic resonance imaging (PET/MRI). Pathological changes in the optic nerve and optic cortex were assessed by immunofluorescence, reactive oxygen species (ROS) kit, and and nicotinamide adenine dinucleotide phosphate (NADPH) kit. Expression of glucose transporter proteins (GLUTs) and key enzymes of the pentose phosphate pathway (PPP) was evaluated using immunofluorescence and western blot. The activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B signaling pathway was analyzed via western blot. RESULTS On day 1 of elevated IOP, the modeled eye exhibited reduced glucose uptake in the corresponding visual cortex compared with the contralateral visual cortex. Over time, the condition gradually improved, with no discernible difference between the two sides by day 21. Concurrently, along with abnormal activation of microglia and progressive reduction of retinal ganglion cells, we noted abnormal expression of glucose transporter proteins in visual cortical neurons. Additionally, elevated levels of ROS and NADPH were observed in both the retinal and brain tissues following IOP elevation. In contrast, administration of the neuroprotectant Apelin-13 mitigated the pathology induced by IOP elevation. Conversely, treatment with a PI3K inhibitor significantly diminished the protective effects of Apelin-13. CONCLUSIONS These findings imply that altered glucose metabolism in the visual center may be an early sign of optic nerve damage in patients with glaucoma. Apelin-13 may rely on the PI3K/Akt signaling pathway to regulate the redistribution of energy metabolism in the retina and visual centers, thereby mitigating oxidative stress and safeguarding neuronal cells.
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Affiliation(s)
- Ya Zhang
- Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, 400042, China
- Department of Ophthalmology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Jia Zhao
- Department of Otolaryngology-Head and Neck Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Jian Zhou
- Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Zhen Jiang
- Department of Ophthalmology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Kaihui Cheng
- Department of Ophthalmology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Caifeng Lei
- Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, 400042, China
| | - Ling Yu
- Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, 400042, China.
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Zhang J, Lu E, Deng L, Zhu Y, Lu X, Li X, Li F, Yan Y, Han JY, Li Y, Zhang Y. Immunological roles for resistin and related adipokines in obesity-associated tumors. Int Immunopharmacol 2024; 142:112911. [PMID: 39232363 DOI: 10.1016/j.intimp.2024.112911] [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: 05/24/2024] [Revised: 08/01/2024] [Accepted: 08/05/2024] [Indexed: 09/06/2024]
Abstract
Rationale Obesity is an independent risk factor for the occurrence and development of tumors. Obesity is influenced by signaling of adipokines, which are secreted factors from adipocytes and resident immune cells within adipose tissues that mediate lipid metabolism. More recently, adipokines have been implicated in chronic inflammation as well as in tumor formation and growth. Among them, resistin has received increasing attention in research related to the growth and expansion of solid tumors and hematological cancers through various signaling pathways. Objective and findings We reviewed the physiological, biochemical, and immune functions of adipose tissue, with a focus on the structure and expression of resistin and adipokines within multiple adipose cell types, their signaling pathways and putative effects on tumor cells, as well as their in vivo regulation. Current evidence indicates that adipokines such as resistin act as pro-inflammatory factors to stimulate immune cells which, in turn, promotes tumor angiogenesis, connective tissue proliferation, and matrix fibrosis. Concurrently, in states of metabolic dysfunction and lipotoxicity in obese individuals, the numbers and functions of immune cells are compromised, leading to an immunosuppressive environment that fosters tumor cell survival and weak cancer immune monitoring. Conclusion Adipokines such as resistin are important to the development of obesity-related tumors. Clarifying the roles for obesity-related factors in immune regulation and tumor progression may lead to the discovery of novel anti-tumor strategies for targeting obesity factors such as resistin to limit tumor growth and manage obesity, or both.
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Affiliation(s)
- Jingxin Zhang
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Enting Lu
- Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Lei Deng
- Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Yaoxuan Zhu
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Xiaoqing Lu
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Xinyuan Li
- School of Nursing, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Fangmei Li
- Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Yan Yan
- Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Jing-Yan Han
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Yin Li
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
| | - Yi Zhang
- Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
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Rathor R, Suryakumar G. Myokines: A central point in managing redox homeostasis and quality of life. Biofactors 2024; 50:885-909. [PMID: 38572958 DOI: 10.1002/biof.2054] [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] [Received: 05/09/2023] [Accepted: 03/15/2024] [Indexed: 04/05/2024]
Abstract
Redox homeostasis is a crucial phenomenon that is obligatory for maintaining the healthy status of cells. However, the loss of redox homeostasis may lead to numerous diseases that ultimately result in a compromised quality of life. Skeletal muscle is an endocrine organ that secretes hundreds of myokines. Myokines are peptides and cytokines produced and released by muscle fibers. Skeletal muscle secreted myokines act as a robust modulator for regulating cellular metabolism and redox homeostasis which play a prime role in managing and improving metabolic function in multiple organs. Further, the secretory myokines maintain redox homeostasis not only in muscles but also in other organs of the body via stabilizing oxidants and antioxidant levels. Myokines are also engaged in maintaining mitochondrial dynamics as mitochondria is a central point for the generation of reactive oxygen species (ROS). Ergo, myokines also act as a central player in communicating signals to other organs, including the pancreas, gut, liver, bone, adipose tissue, brain, and skin via their autocrine, paracrine, or endocrine effects. The present review provides a comprehensive overview of skeletal muscle-secreted myokines in managing redox homeostasis and quality of life. Additionally, probable strategies will be discussed that provide a solution for a better quality of life.
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Affiliation(s)
- Richa Rathor
- Defence Institute of Physiology & Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Ministry of Defence, Delhi, India
| | - Geetha Suryakumar
- Defence Institute of Physiology & Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Ministry of Defence, Delhi, India
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Ziskoven PC, Nogueira AVB, Yoldaş O, Buduneli N, Wild PS, Koeck T, Deschner J. Apelin - A New Kid on the Block in Periodontology. ORAL HEALTH & PREVENTIVE DENTISTRY 2024; 22:417-424. [PMID: 39189510 PMCID: PMC11619819 DOI: 10.3290/j.ohpd.b5695264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 07/08/2024] [Indexed: 08/28/2024]
Abstract
Periodontitis is associated with numerous systemic diseases, and it has been shown that these associations are partly causal in nature. It is assumed that such interactions between periodontal and systemic diseases are also medi- ated via adipokines. Apelin, an adipokine about which there is little research in the dental field, is also produced together with its receptor in periodontal cells. The aim of this review was to summarize the currently available literature on the apelin-APJ system to better understand the pathomechanistic relationship between periodontitis and obesity and to de- termine the potential clinical relevance of apelin for diagnostics and therapy. In vitro studies suggest that apelin can en- hance bacterial-induced synthesis of proinflammatory and proteolytic molecules, indicating a significant etiopathogenic role of this adipokine. Since serum levels of apelin are elevated in diabetes and/or obesity, it is possible that such sys- temic diseases promote the development and progression of periodontitis via apelin. On the other hand, it is also conceivable that apelin from the periodontium influences such systemic diseases. Further research is needed to better understand the role of apelin in the periodontium and the entire oral cavity, but also in the interactions between periodontal and sys- temic diseases. In particular, clinical intervention studies are needed to further decipher the etiopathogenic role of apelin in periodontitis.
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Affiliation(s)
- Pablo Cores Ziskoven
- Dentist, Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. Study conception and design, literature search, data analysis and interpretation, prepared the original draft, edited the manuscript, visualisation, reviewed and approved the final version of the manuscript
| | - Andressa V. B. Nogueira
- Dentist, Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. Study conception and design, literature search, data analysis and interpretation, prepared the original draft, edited the manuscript, visualisation, supervision, reviewed and approved the final version of the manuscript
| | - Onur Yoldaş
- Dentist, Department of Periodontology, School of Dentistry, Ege University, İzmir, Turkey. Study conception and design, literature search, prepared the original draft, edited and reviewed the manuscript, reviewed and approved the final version of the manuscript
| | - Nurcan Buduneli
- Professor, Department of Periodontology, School of Dentistry, Ege University, İzmir, Turkey. Study conception and design, literature search, prepared the original draft, edited and reviewed the manuscript, reviewed and approved the final version of the manuscript
| | - Philipp S. Wild
- Professor, Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Molecular Biology (IMB), Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany. Study conception and design, literature search, prepared the original draft, edited and reviewed the manuscript, supervision, reviewed and approved the final version of the manuscript
| | - Thomas Koeck
- Head of Targeted Proteomic Biomarker Laboratory, Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. Study conception and design, literature search, prepared the original draft, edited and reviewed the manuscript, visualisation, supervision, reviewed and approved the final version of the manuscript
| | - James Deschner
- Professor, Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.Study conception and design, literature search, data analysis and interpretation, prepared the original draft, edited and reviewed the manuscript, visualisation, supervision, reviewed and approved the final version of the manuscript
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Chen ZT, Weng ZX, Lin JD, Meng ZX. Myokines: metabolic regulation in obesity and type 2 diabetes. LIFE METABOLISM 2024; 3:loae006. [PMID: 39872377 PMCID: PMC11749576 DOI: 10.1093/lifemeta/loae006] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 02/23/2024] [Accepted: 02/29/2024] [Indexed: 01/30/2025]
Abstract
Skeletal muscle plays a vital role in the regulation of systemic metabolism, partly through its secretion of endocrine factors which are collectively known as myokines. Altered myokine levels are associated with metabolic diseases, such as type 2 diabetes (T2D). The significance of interorgan crosstalk, particularly through myokines, has emerged as a fundamental aspect of nutrient and energy homeostasis. However, a comprehensive understanding of myokine biology in the setting of obesity and T2D remains a major challenge. In this review, we discuss the regulation and biological functions of key myokines that have been extensively studied during the past two decades, namely interleukin 6 (IL-6), irisin, myostatin (MSTN), growth differentiation factor 11 (GDF11), fibroblast growth factor 21 (FGF21), apelin, brain-derived neurotrophic factor (BDNF), meteorin-like (Metrnl), secreted protein acidic and rich in cysteine (SPARC), β-aminoisobutyric acid (BAIBA), Musclin, and Dickkopf 3 (Dkk3). Related to these, we detail the role of exercise in myokine expression and secretion together with their contributions to metabolic physiology and disease. Despite significant advancements in myokine research, many myokines remain challenging to measure accurately and investigate thoroughly. Hence, new research techniques and detection methods should be developed and rigorously tested. Therefore, developing a comprehensive perspective on myokine biology is crucial, as this will likely offer new insights into the pathophysiological mechanisms underlying obesity and T2D and may reveal novel targets for therapeutic interventions.
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Affiliation(s)
- Zhi-Tian Chen
- Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
- Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
- Zhejiang University-University of Edinburgh Institute (ZJE), School of Medicine, Zhejiang University, Haining, Zhejiang 314400, China
| | - Zhi-Xuan Weng
- Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
- Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Jiandie D Lin
- Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, United States
| | - Zhuo-Xian Meng
- Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
- Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China
- Department of Geriatrics, Affiliated Hangzhou First People’s Hospital, Hangzhou, Zhejiang 310006, China
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Kilpiö T, Skarp S, Perjés Á, Swan J, Kaikkonen L, Saarimäki S, Szokodi I, Penninger JM, Szabó Z, Magga J, Kerkelä R. Apelin regulates skeletal muscle adaptation to exercise in a high-intensity interval training model. Am J Physiol Cell Physiol 2024; 326:C1437-C1450. [PMID: 38525542 DOI: 10.1152/ajpcell.00427.2023] [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: 09/05/2023] [Revised: 03/18/2024] [Accepted: 03/18/2024] [Indexed: 03/26/2024]
Abstract
Plasma apelin levels are reduced in aging and muscle wasting conditions. We aimed to investigate the significance of apelin signaling in cardiac and skeletal muscle responses to physiological stress. Apelin knockout (KO) and wild-type (WT) mice were subjected to high-intensity interval training (HIIT) by treadmill running. The effects of apelin on energy metabolism were studied in primary mouse skeletal muscle myotubes and cardiomyocytes. Apelin increased mitochondrial ATP production and mitochondrial coupling efficiency in myotubes and promoted the expression of mitochondrial genes both in primary myotubes and cardiomyocytes. HIIT induced mild concentric cardiac hypertrophy in WT mice, whereas eccentric growth was observed in the left ventricles of apelin KO mice. HIIT did not affect myofiber size in skeletal muscles of WT mice but decreased the myofiber size in apelin KO mice. The decrease in myofiber size resulted from a fiber type switch toward smaller slow-twitch type I fibers. The increased proportion of slow-twitch type I fibers in apelin KO mice was associated with upregulation of myosin heavy chain slow isoform expression, accompanied with upregulated expression of genes related to fatty acid transport and downregulated expression of genes related to glucose metabolism. Mechanistically, skeletal muscles of apelin KO mice showed defective induction of insulin-like growth factor-1 signaling in response to HIIT. In conclusion, apelin is required for proper skeletal and cardiac muscle adaptation to high-intensity exercise. Promoting apelinergic signaling may have benefits in aging- or disease-related muscle wasting conditions.NEW & NOTEWORTHY Apelin levels decline with age. This study demonstrates that in trained mice, apelin deficiency results in a switch from fast type II myofibers to slow oxidative type I myofibers. This is associated with a concomitant change in gene expression profile toward fatty acid utilization, indicating an aged-muscle phenotype in exercised apelin-deficient mice. These data are of importance in the design of exercise programs for aging individuals and could offer therapeutic target to maintain muscle mass.
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Affiliation(s)
- Teemu Kilpiö
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Sini Skarp
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Ábel Perjés
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Julia Swan
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Leena Kaikkonen
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Samu Saarimäki
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - István Szokodi
- Heart Institute, Medical School, and Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Josef M Penninger
- IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria
- Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - Zoltán Szabó
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Johanna Magga
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
- Biocenter Oulu, University of Oulu, Oulu, Finland
| | - Risto Kerkelä
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
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Park S, Shimokawa I. Influence of Adipokines on Metabolic Dysfunction and Aging. Biomedicines 2024; 12:873. [PMID: 38672227 PMCID: PMC11048512 DOI: 10.3390/biomedicines12040873] [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: 03/19/2024] [Revised: 04/12/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024] Open
Abstract
Currently, 30% of the global population is overweight or obese, with projections from the World Obesity Federation suggesting that this figure will surpass 50% by 2035. Adipose tissue dysfunction, a primary characteristic of obesity, is closely associated with an increased risk of metabolic abnormalities, such as hypertension, hyperglycemia, and dyslipidemia, collectively termed metabolic syndrome. In particular, visceral fat accretion is considered as a hallmark of aging and is strongly linked to higher mortality rates in humans. Adipokines, bioactive peptides secreted by adipose tissue, play crucial roles in regulating appetite, satiety, adiposity, and metabolic balance, thereby rendering them key players in alleviating metabolic diseases and potentially extending health span. In this review, we elucidated the role of adipokines in the development of obesity and related metabolic disorders while also exploring the potential of certain adipokines as candidates for longevity interventions.
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Affiliation(s)
- Seongjoon Park
- Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan;
| | - Isao Shimokawa
- Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan;
- SAGL, Limited Liability Company, 1-4-34, Kusagae, Chuo-ku, Fukuoka 810-0045, Japan
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Devère M, Takhlidjt S, Prévost G, Chartrel N, Leprince J, Picot M. The 26RFa (QRFP)/GPR103 Neuropeptidergic System: A Key Regulator of Energy and Glucose Metabolism. Neuroendocrinology 2024; 115:111-127. [PMID: 38599200 DOI: 10.1159/000538629] [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] [Received: 11/30/2023] [Accepted: 03/28/2024] [Indexed: 04/12/2024]
Abstract
BACKGROUND Obesity and type 2 diabetes are strongly associated pathologies, currently considered as a worldwide epidemic problem. Understanding the mechanisms that drive the development of these diseases would enable to develop new therapeutic strategies for their prevention and treatment. Particularly, the role of the brain in energy and glucose homeostasis has been studied for 2 decades. In specific, the hypothalamus contains well-identified neural networks that regulate appetite and potentially also glucose homeostasis. A new concept has thus emerged, suggesting that obesity and diabetes could be due to a dysfunction of the same, still poorly understood, neural networks. SUMMARY The neuropeptide 26RFa (also termed QRFP) belongs to the family of RFamide regulatory peptides and has been identified as the endogenous ligand of the human G protein-coupled receptor GPR103 (QRFPR). The primary structure of 26RFa is strongly conserved during vertebrate evolution, suggesting its crucial roles in the control of vital functions. Indeed, the 26RFa/GPR103 peptidergic system is reported to be involved in the control of various neuroendocrine functions, notably the control of energy metabolism in which it plays an important role, both centrally and peripherally, since 26RFa regulates feeding behavior, thermogenesis and lipogenesis. Moreover, 26RFa is reported to control glucose homeostasis both peripherally, where it acts as an incretin, and centrally, where the 26RFa/GPR103 system relays insulin signaling in the brain to control glucose metabolism. KEY MESSAGES This review gives a comprehensive overview of the role of the 26RFa/GPR103 system as a key player in the control of energy and glucose metabolism. In a pathophysiological context, this neuropeptidergic system represents a prime therapeutic target whose mechanisms are highly relevant to decipher.
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Affiliation(s)
- Mélodie Devère
- University Rouen Normandie, Inserm, NorDiC UMR 1239, Normandie University, Rouen, France
| | - Saloua Takhlidjt
- University Rouen Normandie, Inserm, NorDiC UMR 1239, Normandie University, Rouen, France
| | - Gaëtan Prévost
- University Rouen Normandie, Inserm, NorDiC UMR 1239, Normandie University, Rouen, France
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Rouen Normandie, Inserm, Normandie University, NorDiC UMR 1239, CHU Rouen, Rouen, France
| | - Nicolas Chartrel
- University Rouen Normandie, Inserm, NorDiC UMR 1239, Normandie University, Rouen, France
| | - Jérôme Leprince
- University Rouen Normandie, Inserm, NorDiC UMR 1239, Normandie University, Rouen, France
- University Rouen Normandie, Normandie University, INSERM US 51, CNRS UAR 2026, HeRacLeS, Rouen, France
| | - Marie Picot
- University Rouen Normandie, Inserm, NorDiC UMR 1239, Normandie University, Rouen, France
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Chapman FA, Maguire JJ, Newby DE, Davenport AP, Dhaun N. Targeting the apelin system for the treatment of cardiovascular diseases. Cardiovasc Res 2023; 119:2683-2696. [PMID: 37956047 PMCID: PMC10757586 DOI: 10.1093/cvr/cvad171] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 06/12/2023] [Accepted: 06/15/2023] [Indexed: 11/15/2023] Open
Abstract
Cardiovascular disease is the leading cause of death worldwide. Its prevalence is rising due to ageing populations and the increasing incidence of diseases such as chronic kidney disease, obesity, and diabetes that are associated with elevated cardiovascular risk. Despite currently available treatments, there remains a huge burden of cardiovascular disease-associated morbidity for patients and healthcare systems, and newer treatments are needed. The apelin system, comprising the apelin receptor and its two endogenous ligands apelin and elabela, is a broad regulator of physiology that opposes the actions of the renin-angiotensin and vasopressin systems. Activation of the apelin receptor promotes endothelium-dependent vasodilatation and inotropy, lowers blood pressure, and promotes angiogenesis. The apelin system appears to protect against arrhythmias, inhibits thrombosis, and has broad anti-inflammatory and anti-fibrotic actions. It also promotes aqueous diuresis through direct and indirect (central) effects in the kidney. Thus, the apelin system offers therapeutic promise for a range of cardiovascular, kidney, and metabolic diseases. This review will discuss current cardiovascular disease targets of the apelin system and future clinical utility of apelin receptor agonism.
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Affiliation(s)
- Fiona A Chapman
- BHF/University of Edinburgh Centre for Cardiovascular Science, Queen's Medical Research Institute, Edinburgh, UK
- Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Janet J Maguire
- Division of Experimental Medicine and Immunotherapeutics, Addenbrooke's Centre for Clinical Investigation, University of Cambridge, Cambridge, UK
| | - David E Newby
- BHF/University of Edinburgh Centre for Cardiovascular Science, Queen's Medical Research Institute, Edinburgh, UK
| | | | - Neeraj Dhaun
- BHF/University of Edinburgh Centre for Cardiovascular Science, Queen's Medical Research Institute, Edinburgh, UK
- Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK
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11
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Pahlavani HA, Laher I, Weiss K, Knechtle B, Zouhal H. Physical exercise for a healthy pregnancy: the role of placentokines and exerkines. J Physiol Sci 2023; 73:30. [PMID: 37964253 PMCID: PMC10718036 DOI: 10.1186/s12576-023-00885-1] [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: 08/14/2023] [Accepted: 10/20/2023] [Indexed: 11/16/2023]
Abstract
Complications such as diabetes and preeclampsia can occur during pregnancy. Moderate-intensity exercise can prevent such complications by releasing placentokines and exerkines, such as apelin, adiponectin, leptin, irisin, and chemerin. Exercise and apelin increase thermogenesis and glucose uptake in pregnancy by activating AMPK, PI3K, PGC-1α, AKT1, UCP3, and sarcolipin. Exercise increases apelin levels to reduce preeclampsia symptoms by increasing eNOS, NO, placental growth factor (PlGF), and VEGF and decreasing levels of fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), and oxidative stress. A negative relationship has been reported between plasma leptin and VO2peak/kg and VO2peak in women with gestational diabetes. In active women, decreases in leptin levels reduce the risk of preeclampsia by ~ 40%. Higher adiponectin levels are associated with greater physical activity and lead to increased insulin sensitivity. Increased adiponectin levels in preeclampsia and exercise counteract inflammatory and atherogenic activities while also having vascular protective effects. Exercise increases irisin levels that correlate negatively with fasting glucose, insulin concentration, and glycosylated hemoglobin levels. Irisin augments mRNA expression levels of UCP1 and cell death-inducing DNA fragmentation factor-like effector A (cidea) to cause browning of adipose tissue, increased thermogenesis, and increased energy consumption. Irisin concentrations in mothers with preeclampsia in the third trimester negatively correlate with systolic and diastolic blood pressure. Expression levels of chemerin, IL-6, and TNF-α are increased in gestational diabetes, and the increases in chemerin in late pregnancy positively correlate with the ratio of sFlt-1 to PlGF as a marker of preeclampsia. The effects of physical exercise on placentokines and exerkines in women at various stages of pregnancy remain poorly understood.
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Affiliation(s)
| | - Ismail Laher
- Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Katja Weiss
- Institute of Primary Care, University of Zurich, Zurich, Switzerland
| | - Beat Knechtle
- Institute of Primary Care, University of Zurich, Zurich, Switzerland.
- Medbase St Gallen Am Vadianplatz, Vadianstrasse 26, 9001, St. Gallen, Switzerland.
| | - Hassane Zouhal
- Movement Sport, Health and Sciences Laboratory (M2S) UFR-STAPS, University of Rennes 2-ENS Cachan, Charles Tillon, France.
- Institut International Des Sciences Du Sport (2IS), Irodouer, France.
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12
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Pisarenko OI, Studneva IM. Apelin C-Terminal Fragments: Biological Properties and Therapeutic Potential. BIOCHEMISTRY. BIOKHIMIIA 2023; 88:1874-1889. [PMID: 38105205 DOI: 10.1134/s0006297923110160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 09/10/2023] [Accepted: 09/11/2023] [Indexed: 12/19/2023]
Abstract
Creation of bioactive molecules for treatment of cardiovascular diseases based on natural peptides is the focus of intensive experimental research. In the recent years, it has been established that C-terminal fragments of apelin, an endogenous ligand of the APJ receptor, reduce metabolic and functional disorders in experimental heart damage. The review presents literature data and generalized results of our own experiments on the effect of apelin-13, [Pyr]apelin-13, apelin-12, and their chemically modified analogues on the heart under normal and pathophysiological conditions in vitro and in vivo. It has been shown that the spectrum of action of apelin peptides on the damaged myocardium includes decrease in the death of cardiomyocytes from necrosis, reduction of damage to cardiomyocyte membranes, improvement in myocardial metabolic state, and decrease in formation of reactive oxygen species and lipid peroxidation products. The mechanisms of protective action of these peptides associated with activation of the APJ receptor and manifestation of antioxidant properties are discussed. The data presented in the review show promise of the molecular design of APJ receptor peptide agonists, which can serve as the basis for the development of cardioprotectors that affect the processes of free radical oxidation and metabolic adaptation.
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Affiliation(s)
- Oleg I Pisarenko
- Chazov National Medical Research Center of Cardiology, Moscow, 121552, Russia.
| | - Irina M Studneva
- Chazov National Medical Research Center of Cardiology, Moscow, 121552, Russia
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13
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Shokrollahi B, Zheng HY, Ma XY, Shang JH. The effects of apelin on IGF1/FSH-induced steroidogenesis, proliferation, Bax expression, and total antioxidant capacity in granulosa cells of buffalo ovarian follicles. Vet Res Commun 2023; 47:1523-1533. [PMID: 37036601 DOI: 10.1007/s11259-023-10107-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: 12/30/2022] [Accepted: 03/15/2023] [Indexed: 04/11/2023]
Abstract
Apelin (APLN) was believed to be an adipokine secreted from adipose tissue. However, studies demonstrate that it is a pleiotropic peptide and has several effects on the female reproductive system. In this study, We examined the effects of different doses of IGF1 and FSH in the presence of APLN-13 on the production of progesterone in buffalo ovary granulosa cells. Furthermore, different doses of APLN isoforms (APLN-13 and APLN-17) were tested on proliferation, Bax protein expression, and antioxidant capacity in the same cells. Granulosa cells of buffalo ovaries were cultured in the presence of different doses of IGF1 and FSH with or without APLN-13 (10-9 M) to evaluate its effect on the secretion of progesterone tested by ELISA assay. The WST-1 method was used to survey the effect of APLN on granulosa cell proliferation and cytotoxicity. In addition, the antioxidant capacity of the cells in the presence of APLN was assessed using the FRAP method. mRNA and Bax protein levels were measured in granulosa cells treated with APLN using real-time PCR and western blot techniques. APLN-13 (10-9) stimulated the effect of IGF1 on the production of progesterone, and its levels were affected by APLN-13 dose-dependently. However, it did not significantly stimulate the effect of FSH on the secretion of progesterone. APLN-13 (all doses) and APLN-17 (10-8 and 10-9 M) improved the proliferation of granulosa cells. Moreover, preincubation of the cells for an hour by APLN receptor antagonist (ML221, 10 µM) did not significantly affect the proliferation of cells induced by APLN. Neither APLN-13 nor APLN-17 were not cytotoxic for the cells compared to the control treatment. APLN-13 at the doses of 10-6 and 10-8 M substantially up and down-regulated Bax protein expression; however, such effects were not observed when the cells were preincubated with ML221. In addition, APLN-17 did not influence the expression amount of Bax. Furthermore, both APLN-13 and -17 improved the total antioxidant capacity of the ovarian granulosa cells, but such effects were not seen when the cells were preincubated with ML221. According to these results, APLN enhanced the steroidogenesis induced by IGF1 but did not affect the steroidogenesis induced by FSH. APLN also enhanced the cell proliferation and antioxidant capacity of buffalo ovaries follicular granulosa cells; however, its effect on Bax expression was different.
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Affiliation(s)
- Borhan Shokrollahi
- Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, 530001, China
- Department of Animal Science, Sanandaj Branch, Islamic Azad University, Sanandaj, Kurdistan, Iran
| | - Hai-Ying Zheng
- Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, 530001, China
| | - Xiao-Ya Ma
- Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, 530001, China
| | - Jiang-Hua Shang
- Key Laboratory of Buffalo Genetics, Breeding and Reproduction Technology, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Sciences, Nanning, 530001, China.
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14
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Nishii K, Aizu N, Yamada K. Review of the health-promoting effects of exercise and the involvement of myokines. FUJITA MEDICAL JOURNAL 2023; 9:171-178. [PMID: 37554940 PMCID: PMC10405897 DOI: 10.20407/fmj.2022-020] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/17/2022] [Indexed: 08/10/2023]
Abstract
Exercise reduces the risk of obesity-based, lifestyle-related diseases, such as metabolic abnormalities and cardiovascular diseases. The present review covers the health-promoting effects of exercise from the point of view of the physiologically active factor myokine, which is secreted by skeletal muscle, and focuses on the skeletal muscle as a new endocrine organ. Myokines have various effects, such as preventing metabolic syndrome by breaking down fat, preventing diabetes by improving glucose metabolism, and preventing progression of arteriosclerosis, dementia, and osteoporosis by enhancing bone metabolism. These substances also stabilize blood pressure, prevent cancer, increase immunity against infections, and prevent the development of age-associated diseases. Myokines are secreted by skeletal muscle into blood vessels, allowing them to exert systemic endocrine effects in organs throughout the body. Myokines are involved in bodily homeostasis and adaptation to the environment, and function by a mechanism similar to that of the skeletal muscle mass regulatory mechanism. Determining the relationships between multiple organs and their biological significance is important for exercise and health research. Progress in this field is expected to result in the identification of pathological mechanisms of action, development of new drugs, evaluation of the effectiveness of biomarkers over a wide range, and future improvement in healthcare.
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Affiliation(s)
- Kazuhiro Nishii
- Major in Health Sciences, Graduate School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan
- Faculty of Rehabilitation, School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan
| | - Naoki Aizu
- Major in Health Sciences, Graduate School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan
| | - Kouji Yamada
- Major in Health Sciences, Graduate School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan
- Faculty of Rehabilitation, School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan
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15
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Mehri K, Hamidian G, Zavvari Oskuye Z, Nayebirad S, Farajdokht F. The role of apelinergic system in metabolism and reproductive system in normal and pathological conditions: an overview. Front Endocrinol (Lausanne) 2023; 14:1193150. [PMID: 37424869 PMCID: PMC10324965 DOI: 10.3389/fendo.2023.1193150] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 06/06/2023] [Indexed: 07/11/2023] Open
Abstract
Lifestyle changes have made metabolic disorders as one of the major threats to life. Growing evidence demonstrates that obesity and diabetes disrupt the reproductive system by affecting the gonads and the hypothalamus-pituitary-gonadal (HPG) axis. Apelin, an adipocytokine, and its receptor (APJ) are broadly expressed in the hypothalamus nuclei, such as paraventricular and supraoptic, where gonadotropin-releasing hormone (GnRH) is released, and all three lobes of the pituitary, indicating that apelin is involved in the control of reproductive function. Moreover, apelin affects food intake, insulin sensitivity, fluid homeostasis, and glucose and lipid metabolisms. This review outlined the physiological effects of the apelinergic system, the relationship between apelin and metabolic disorders such as diabetes and obesity, as well as the effect of apelin on the reproductive system in both gender. The apelin-APJ system can be considered a potential therapeutic target in the management of obesity-associated metabolic dysfunction and reproductive disorders.
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Affiliation(s)
- Keyvan Mehri
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Gholamreza Hamidian
- Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | | | - Sepehr Nayebirad
- Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Fereshteh Farajdokht
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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16
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An C, Pipia I, Ruiz AS, Argüelles I, An M, Wase S, Peng G. The molecular link between obesity and genomic instability in cancer development. Cancer Lett 2023; 555:216035. [PMID: 36502927 DOI: 10.1016/j.canlet.2022.216035] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 11/10/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022]
Abstract
Obesity has been known to be a major risk factor for various types of cancers for several decades. More recently, the relationship between dysregulated adipokines and cancer development has been the focus of much research. Adipose tissue is an important endocrine organ that secretes adipokines that affect both autocrine and paracrine signaling. These adipokines modulate inflammation, induce insulin resistance, and regulate their own behavior and production. Adipokine-production dysregulation is due to physiological changes in adipose tissue that prompt molecular modifications, including low-grade inflammation and the stimulatory production of reactive oxygen species. Additionally, studies have linked DNA damage response, genomic instability, and the innate immune response to tumorigenesis. Further investigation of adipokines and their role in the promotion of genomic instability may clarify the link between obesity and cancer, as well as elucidate potential pharmaceutical targets. In this review, we discuss the progress of recent literature, focusing on the impact of adipokines, genomic instability, and the innate immune response on increasing the risk of cancer.
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Affiliation(s)
- Clemens An
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The Robert Larner, M.D. College of Medicine at The University of Vermont, Burlington, VT, USA.
| | - Ilissa Pipia
- Department of Biological Sciences, Cornell University, Ithaca, NY, USA
| | - Ana-Sofia Ruiz
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ivonne Argüelles
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Martino An
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Saima Wase
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Otolaryngology - Head & Neck Surgery, University of North Carolina Medical Center, Chapel Hill, NC, USA
| | - Guang Peng
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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17
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Epidemiological, mechanistic, and practical bases for assessment of cardiorespiratory fitness and muscle status in adults in healthcare settings. Eur J Appl Physiol 2023; 123:945-964. [PMID: 36683091 PMCID: PMC10119074 DOI: 10.1007/s00421-022-05114-y] [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: 07/26/2022] [Accepted: 12/08/2022] [Indexed: 01/24/2023]
Abstract
Given their importance in predicting clinical outcomes, cardiorespiratory fitness (CRF) and muscle status can be considered new vital signs. However, they are not routinely evaluated in healthcare settings. Here, we present a comprehensive review of the epidemiological, mechanistic, and practical bases of the evaluation of CRF and muscle status in adults in primary healthcare settings. We highlight the importance of CRF and muscle status as predictors of morbidity and mortality, focusing on their association with cardiovascular and metabolic outcomes. Notably, adults in the best quartile of CRF and muscle status have as low as one-fourth the risk of developing some of the most common chronic metabolic and cardiovascular diseases than those in the poorest quartile. The physiological mechanisms that underlie these epidemiological associations are addressed. These mechanisms include the fact that both CRF and muscle status reflect an integrative response to the body function. Indeed, muscle plays an active role in the development of many diseases by regulating the body's metabolic rate and releasing myokines, which modulate metabolic and cardiovascular functions. We also go over the most relevant techniques for assessing peak oxygen uptake as a surrogate of CRF and muscle strength, mass, and quality as surrogates of muscle status in adults. Finally, a clinical case of a middle-aged adult is discussed to integrate and summarize the practical aspects of the information presented throughout. Their clinical importance, the ease with which we can assess CRF and muscle status using affordable techniques, and the availability of reference values, justify their routine evaluation in adults across primary healthcare settings.
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18
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Effect of eight weeks of vitamin D supplementation and water-based exercise on cardiometabolic profile in women with type 2 diabetes. Sci Sports 2023. [DOI: 10.1016/j.scispo.2022.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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19
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Llanos P, Palomero J. Reactive Oxygen and Nitrogen Species (RONS) and Cytokines-Myokines Involved in Glucose Uptake and Insulin Resistance in Skeletal Muscle. Cells 2022; 11:cells11244008. [PMID: 36552772 PMCID: PMC9776436 DOI: 10.3390/cells11244008] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/05/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
Insulin resistance onset in skeletal muscle is characterized by the impairment of insulin signaling, which reduces the internalization of glucose, known as glucose uptake, into the cell. Therefore, there is a deficit of intracellular glucose, which is the main source for energy production in the cell. This may compromise cellular viability and functions, leading to pathological dysfunction. Skeletal muscle fibers continuously generate reactive oxygen and nitrogen species (RONS). An excess of RONS produces oxidative distress, which may evoke cellular damage and dysfunction. However, a moderate level of RONS, which is called oxidative eustress, is critical to maintain, modulate and regulate cellular functions through reversible interactions between RONS and the components of cellular signaling pathways that control those functions, such as the facilitation of glucose uptake. The skeletal muscle releases peptides called myokines that may have endocrine and paracrine effects. Some myokines bind to specific receptors in skeletal muscle fibers and might interact with cellular signaling pathways, such as PI3K/Akt and AMPK, and facilitate glucose uptake. In addition, there are cytokines, which are peptides produced by non-skeletal muscle cells, that bind to receptors at the plasma membrane of skeletal muscle cells and interact with the cellular signaling pathways, facilitating glucose uptake. RONS, myokines and cytokines might be acting on the same signaling pathways that facilitate glucose uptake in skeletal muscle. However, the experimental studies are limited and scarce. The aim of this review is to highlight the current knowledge regarding the role of RONS, myokines and cytokines as potential signals that facilitate glucose uptake in skeletal muscle. In addition, we encourage researchers in the field to lead and undertake investigations to uncover the fundamentals of glucose uptake evoked by RONS, myokines, and cytokines.
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Affiliation(s)
- Paola Llanos
- Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago 8380544, Chile
- Centro de Estudios en Ejercicio, Metabolismo y Cáncer, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
| | - Jesus Palomero
- Department of Physiology and Pharmacology, Faculty of Medicine, Campus Miguel de Unamuno, Universidad de Salamanca, Av. Alfonso X El Sabio, 37007 Salamanca, Spain
- Institute of Neurosciences of Castilla y León (INCyL), 37007 Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
- Correspondence: ; Tel.: +34-666-589-153
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20
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Janssens P, Decuypere JP, Bammens B, Llorens-Cortes C, Vennekens R, Mekahli D. The emerging role of the apelinergic system in kidney physiology and disease. Nephrol Dial Transplant 2022; 37:2314-2326. [PMID: 33744967 DOI: 10.1093/ndt/gfab070] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Indexed: 12/31/2022] Open
Abstract
The apelinergic system (AS) is a novel pleiotropic system with an essential role in renal and cardiovascular physiology and disease, including water homeostasis and blood pressure regulation. It consists of two highly conserved peptide ligands, apelin and apela, and a G-protein-coupled apelin receptor. The two ligands have many isoforms and a short half-life and exert both similar and divergent effects. Vasopressin, apelin and their receptors colocalize in hypothalamic regions essential for body fluid homeostasis and interact at the central and renal levels to regulate water homeostasis and diuresis in inverse directions. In addition, the AS and renin-angiotensin system interact both systemically and in the kidney, with implications for the cardiovascular system. A role for the AS in diverse pathological states, including disorders of sodium and water balance, hypertension, heart failure, pre-eclampsia, acute kidney injury, sepsis and diabetic nephropathy, has recently been reported. Furthermore, several metabolically stable apelin analogues have been developed, with potential applications in diverse diseases. We review here what is currently known about the physiological functions of the AS, focusing on renal, cardiovascular and metabolic homeostasis, and the role of the AS in associated diseases. We also describe several hurdles and research opportunities worthy of the attention of the nephrology community.
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Affiliation(s)
- Peter Janssens
- PKD Research Group, Laboratory of Pediatrics, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.,Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussell), Department of Nephrology, Laarbeeklaan 101, 1090 Brussels, Belgium
| | - Jean-Paul Decuypere
- PKD Research Group, Laboratory of Pediatrics, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
| | - Bert Bammens
- Department of Nephrology, Dialysis and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.,Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Catherine Llorens-Cortes
- Laboratory of Central Neuropeptides in the Regulation of Body Fluid Homeostasis and Cardiovascular Functions, Center for Interdisciplinary Research in Biology, Collège de France, INSERM U1050, CNRS UMR 7241, Paris, France
| | - Rudi Vennekens
- Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, VIB-KU Leuven Center for Brain and Disease, KU Leuven, Leuven, Belgium and
| | - Djalila Mekahli
- PKD Research Group, Laboratory of Pediatrics, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.,Department of Pediatric Nephrology and Organ Transplantation, University Hospitals Leuven, Leuven, Belgium
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21
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Zamboni M, Mazzali G, Brunelli A, Saatchi T, Urbani S, Giani A, Rossi AP, Zoico E, Fantin F. The Role of Crosstalk between Adipose Cells and Myocytes in the Pathogenesis of Sarcopenic Obesity in the Elderly. Cells 2022; 11:3361. [PMID: 36359757 PMCID: PMC9655977 DOI: 10.3390/cells11213361] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/08/2022] [Accepted: 10/14/2022] [Indexed: 11/15/2023] Open
Abstract
As a result of aging, body composition changes, with a decline in muscle mass and an increase in adipose tissue (AT), which reallocates from subcutaneous to visceral depots and stores ectopically in the liver, heart and muscles. Furthermore, with aging, muscle and AT, both of which have recognized endocrine activity, become dysfunctional and contribute, in the case of positive energy balance, to the development of sarcopenic obesity (SO). SO is defined as the co-existence of excess adiposity and low muscle mass and function, and its prevalence increases with age. SO is strongly associated with greater morbidity and mortality. The pathogenesis of SO is complex and multifactorial. This review focuses mainly on the role of crosstalk between age-related dysfunctional adipose and muscle cells as one of the mechanisms leading to SO. A better understanding of this mechanisms may be useful for development of prevention strategies and treatments aimed at reducing the occurrence of SO.
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Affiliation(s)
- Mauro Zamboni
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Gloria Mazzali
- Geriatrics Division, Department of Medicine, University of Verona, 37126 Verona, Italy
| | - Anna Brunelli
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Tanaz Saatchi
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Silvia Urbani
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Anna Giani
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Andrea P. Rossi
- Geriatrics Division, Department of Medicine, AULSS2, Ospedale Ca’Foncello, 31100 Treviso, Italy
| | - Elena Zoico
- Geriatrics Division, Department of Medicine, University of Verona, 37126 Verona, Italy
| | - Francesco Fantin
- Geriatrics Division, Department of Medicine, University of Verona, 37126 Verona, Italy
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22
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Pérez-López FR, Wu JN, Yao L, López-Baena MT, Pérez-Roncero GR, Varikasuvu SR. Apelin levels in pregnant women with and without gestational diabetes mellitus: a collaborative systematic review and meta-analysis. Gynecol Endocrinol 2022; 38:803-812. [PMID: 36002980 DOI: 10.1080/09513590.2022.2114450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 08/05/2022] [Accepted: 08/12/2022] [Indexed: 12/13/2022] Open
Abstract
Aims: This systematic review and meta-analysis investigated maternal apelin levels in pregnant women with and without GDM. Secondary outcomes were glucose- and lipid-related results.Methods: Databases including PubMed, Embase, Cochrane Library, LILACS, CNKI, and Wang Fang were searched. The methodological quality of included studies was evaluated with the Newcastle-Ottawa Scale. Mean differences (MDs) or standardized MDs (SMDs) with their 95% confidence intervals (CIs) were evaluated. Random effect model analyses were carried out and heterogeneity with the I2 and Tau2 statistics.Results: Fourteen observational studies (sample size: 1033 women with GDM and 1053 for control women) with a low or moderate risk of bias were included in the analysis. During the second half of pregnancy, maternal apelin estimate was significantly higher in women with GDM (SMD = 0.64; 95% CI: 0.03 to 1.25), as well as insulin (SMD = 1.41% CI: 0.84 to 1.99), glucose (SMD = 1.56; 95% CI 1.20 to 1.91), glycated hemoglobin (SMD = 1.11, 95% CI: 0.69 to 1.54), HOMA-IR (MD = 2.25; 95%CI: 1.51 to 2.98), BMI (MD = 0.80 kg/m2, 95%CI: 0.52 to 1.08), total cholesterol (SMD = 0.42, 0.12 to 0.73), LDL-cholesterol (SMD = 0.63, 95%CI: 0.23 to 1.02), and triglycerides (SMD = 0.40, 95%CI: 0.19 to 0.61) as compared to control women. There was heterogeneity between studies as evidence by high I2 values. Meta-regression analysis indicated statistically significant regression coefficients for age of women, glucose and total cholesterol.Conclusions: GDM was associated with increased circulating apelin, insulin, glucose, glycated hemoglobin, total cholesterol, LDL-cholesterol levels, and HOMA-IR index.
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Affiliation(s)
- Faustino R Pérez-López
- Health Outcomes and Systematic Analyses, Aragón Health Research Institute, Zaragoza, Spain
- Faculty of Medicine, University of Zaragoza, Zaragoza, Spain
| | - Jiang-Nan Wu
- Research Institute, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Li Yao
- Research Institute, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - María T López-Baena
- Health Outcomes and Systematic Analyses, Aragón Health Research Institute, Zaragoza, Spain
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Kon M, Tanimura Y, Yoshizato H. Effects of acute endurance exercise on follistatin-like 1 and apelin in the circulation and metabolic organs in rats. Arch Physiol Biochem 2022; 128:1254-1258. [PMID: 32412800 DOI: 10.1080/13813455.2020.1764050] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Context: Follistatin-like 1 (FSTL1) and apelin exert a favourable effect on energy metabolism.Objective: We examined the effects of acute endurance exercise on the levels of FSTL1 and apelin in the serum and metabolic organs of rats.Methods: Rats were divided into two groups: a sedentary control (CON, n = 8) group and exercise (EX, n = 8) group. The EX group was made to run on a treadmill at 15-30 m/min for 35 min. Immediately after exercise, the blood, skeletal muscles, adipose, heart, and liver were collected; the levels of FSTL1 and apelin were measured.Results: Serum FSTL1 and apelin were significantly increased following acute exercise; in contrast, the levels of FSTL1 and apelin in the tissues were not affected.Conclusions: Acute endurance exercise may stimulate the secretion of FSTL1 and apelin into the circulation, however, the origin of their increased secreted levels may not be the metabolic organs.
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Affiliation(s)
- Michihiro Kon
- School of International Liberal Studies, Chukyo University, Nagoya, Japan
| | - Yuko Tanimura
- Faculty of Human Health, Aichi Toho University, Nagoya, Japan
| | - Hideo Yoshizato
- Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Nagoya, Japan
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Portilla-Martínez A, Ortiz-Flores MÁ, Meaney E, Villarreal F, Nájera N, Ceballos G. (-)-Epicatechin Is a Biased Ligand of Apelin Receptor. Int J Mol Sci 2022; 23:8962. [PMID: 36012227 PMCID: PMC9409145 DOI: 10.3390/ijms23168962] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 07/29/2022] [Accepted: 08/02/2022] [Indexed: 11/24/2022] Open
Abstract
(-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids and is widely distributed in the plant kingdom. Several studies have shown the beneficial effects of EC consumption. Many of these reported effects are exerted by activating the signaling pathways associated with the activation of two specific receptors: the G protein-coupled estrogen receptor (GPER), a transmembrane receptor, and the pregnane X receptor (PXR), which is a nuclear receptor. However, the effects of EC are so diverse that these two receptors cannot describe the complete phenomenon. The apelin receptor or APLNR is classified within the G protein-coupled receptor (GPCR) family, and is capable of activating the G protein canonical pathways and the β-arrestin transducer, which participates in the phenomenon of receptor desensitization and internalization. β-arrestin gained interest in selective pharmacology and mediators of the so-called "biased agonism". With molecular dynamics (MD) and in vitro assays, we demonstrate how EC can recruit the β-arrestin in the active conformation of the APLN receptor acting as a biased agonist.
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Affiliation(s)
- Andrés Portilla-Martínez
- Laboratorio de Investigación Integral Cardiometabólica, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico
| | - Miguel Ángel Ortiz-Flores
- Laboratorio de Investigación Integral Cardiometabólica, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico
| | - Eduardo Meaney
- Laboratorio de Investigación Integral Cardiometabólica, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico
| | | | - Nayelli Nájera
- Laboratorio de Investigación Integral Cardiometabólica, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico
| | - Guillermo Ceballos
- Laboratorio de Investigación Integral Cardiometabólica, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico
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Reiterer M, Gilani A, Lo JC. Pancreatic Islets as a Target of Adipokines. Compr Physiol 2022; 12:4039-4065. [PMID: 35950650 DOI: 10.1002/cphy.c210044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Rising rates of obesity are intricately tied to the type 2 diabetes epidemic. The adipose tissues can play a central role in protection against or triggering metabolic diseases through the secretion of adipokines. Many adipokines may improve peripheral insulin sensitivity through a variety of mechanisms, thereby indirectly reducing the strain on beta cells and thus improving their viability and functionality. Such effects will not be the focus of this article. Rather, we will focus on adipocyte-secreted molecules that have a direct effect on pancreatic islets. By their nature, adipokines represent potential druggable targets that can reach the islets and improve beta-cell function or preserve beta cells in the face of metabolic stress. © 2022 American Physiological Society. Compr Physiol 12:1-27, 2022.
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Affiliation(s)
- Moritz Reiterer
- Division of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Cardiovascular Research Institute, Weill Cornell Medicine, New York, New York, USA
| | - Ankit Gilani
- Division of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Cardiovascular Research Institute, Weill Cornell Medicine, New York, New York, USA
| | - James C Lo
- Division of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Cardiovascular Research Institute, Weill Cornell Medicine, New York, New York, USA
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Çalişkan P, Çağlar TR, Seyit H, Çağlar HG, Vural M, Kural A. Effect of Laparoscopic Sleeve Gastrectomy on Serum Levels of Resistin, Visfatin, and Apelin. Bariatr Surg Pract Patient Care 2022. [DOI: 10.1089/bari.2021.0130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Pınar Çalişkan
- Department of Medical Biochemistry, Faculty of Medicine, University of Health Sciences, Istanbul, Turkey
| | - Tuba Rana Çağlar
- Department of Medical Biochemistry, Faculty of Medicine, University of Health Sciences, Istanbul, Turkey
| | - Hakan Seyit
- Department of General Surgery, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Hifa Gülru Çağlar
- Department of Medical Biochemistry, Faculty of Medicine, University of Health Sciences, Istanbul, Turkey
| | - Meltem Vural
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, University of Health Sciences, Istanbul, Turkey
| | - Alev Kural
- Department of Medical Biochemistry, Faculty of Medicine, University of Health Sciences, Istanbul, Turkey
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Li M, Chi X, Wang Y, Setrerrahmane S, Xie W, Xu H. Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther 2022; 7:216. [PMID: 35794109 PMCID: PMC9259665 DOI: 10.1038/s41392-022-01073-0] [Citation(s) in RCA: 315] [Impact Index Per Article: 105.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 06/15/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
The centenary of insulin discovery represents an important opportunity to transform diabetes from a fatal diagnosis into a medically manageable chronic condition. Insulin is a key peptide hormone and mediates the systemic glucose metabolism in different tissues. Insulin resistance (IR) is a disordered biological response for insulin stimulation through the disruption of different molecular pathways in target tissues. Acquired conditions and genetic factors have been implicated in IR. Recent genetic and biochemical studies suggest that the dysregulated metabolic mediators released by adipose tissue including adipokines, cytokines, chemokines, excess lipids and toxic lipid metabolites promote IR in other tissues. IR is associated with several groups of abnormal syndromes that include obesity, diabetes, metabolic dysfunction-associated fatty liver disease (MAFLD), cardiovascular disease, polycystic ovary syndrome (PCOS), and other abnormalities. Although no medication is specifically approved to treat IR, we summarized the lifestyle changes and pharmacological medications that have been used as efficient intervention to improve insulin sensitivity. Ultimately, the systematic discussion of complex mechanism will help to identify potential new targets and treat the closely associated metabolic syndrome of IR.
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Affiliation(s)
- Mengwei Li
- The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, China
- State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China
| | - Xiaowei Chi
- Development Center for Medical Science & Technology National Health Commission of the People's Republic of China, 100044, Beijing, China
| | - Ying Wang
- The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, China
- State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China
| | | | - Wenwei Xie
- The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, China
- State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China
| | - Hanmei Xu
- The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, China.
- State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China.
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Mohammad M, Karim D, Mehdi M, Marziyeh S, Hadi S, Shila N. The Combinatory Effect of Spirulina Supplementation and Resistance Exercise on Plasma Contents of Adipolin, Apelin, Ghrelin, and Glucose in Overweight and Obese Men. Mediators Inflamm 2022; 2022:9539286. [PMID: 35733519 PMCID: PMC9208992 DOI: 10.1155/2022/9539286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 02/16/2022] [Accepted: 03/26/2022] [Indexed: 11/18/2022] Open
Abstract
Methods The current investigation was conducted in a single-blind and quasiexperimental fashion. Sixty overweight and obese men (BMI > 25) ranging in age from 30 to 55 years were purposefully selected and randomly assigned to one of four groups: training plus spirulina (T+S), training plus placebo (T+P), spirulina (S), or placebo (P). For eight weeks, the (S) and (P) groups consumed two 500 mg spirulina and placebo capsules daily, respectively. Resistance training was performed three sessions a week over eight weeks, consisting of 12 movements with 1-, 2-, 3-, and 4-minute rest intervals and 40-90 percent maximal repetition. Adipolin, apelin, and ghrelin indices were measured before and after exercise using special kits. Results All variables changed significantly between groups except for apelin. Within-group comparisons revealed a substantial increase in adipolin levels in the (T+S) and (T+P) groups (P < 0.05). Apelin levels were decreased in the (T+S) and (T+P) groups. Additionally, FBS levels reduced significantly in (T+S) (P = 0.01). Conclusion It seems that eight weeks of circuit resistance training and spirulina supplementation can lead to reduced weight and apelin and FBS levels as well as increased concentrations of adipolin and ghrelin contents in overweight and obese men.
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Affiliation(s)
- Malekaneh Mohammad
- Department of Clinical Biochemistry, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Dehghani Karim
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Birjand, Birjand, Iran
| | - Mogharnasi Mehdi
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Birjand, Birjand, Iran
| | - Saghebjoo Marziyeh
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Birjand, Birjand, Iran
| | - Sarir Hadi
- Department of Animal Sciences, University of Birjand, Birjand, Iran
| | - Nayebifar Shila
- Department of Sport Sciences, Faculty of Educational Sciences and Psychology, University of Sistan and Baluchestan, Zahedan, Iran
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Luo J, Zhao Q, Li Z, Chen L. Multiple roles of apelin/APJ system in eye diseases. Peptides 2022; 152:170767. [PMID: 35181348 DOI: 10.1016/j.peptides.2022.170767] [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] [Received: 10/29/2021] [Revised: 02/11/2022] [Accepted: 02/12/2022] [Indexed: 10/19/2022]
Abstract
Apelin is an endogenous ligand of G protein-coupled receptor (APJ), and they compose apelin/APJ system. Apelin/APJ system is widely distributed in tissues and plays pleiotropic roles. Attractively, more emphasis has recently been placed on the effects of apelin/APJ system in eye diseases, such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and diabetic macular edema (DME). In this review, we elaborated the roles of apelin/APJ system in the pathophysiological processes of eye. Concretely, apelin/APJ system induces retinal gliosis and angiogenesis. Hypoxia-inducible factors (HIFs) are involved in apelin/APJ system-triggered ROP progress. Apelin/APJ system mediates DR-induced retinopathy. Apelin/APJ system maintains retinal functions and health by protecting Müller cells from apoptosis. Apelin/APJ system suppresses the NMDA-induced retinal ganglion cell (RGC) loss to protect optic nerve damage. Overall, apelin/APJ system is a potential therapeutic target for eye disease.
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Affiliation(s)
- Jingshun Luo
- Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
| | - Qun Zhao
- Health Management Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhiyue Li
- Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
| | - Linxi Chen
- Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.
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Re Cecconi AD, Barone M, Forti M, Lunardi M, Cagnotto A, Salmona M, Olivari D, Zentilin L, Resovi A, Persichitti P, Belotti D, Palo F, Takakura N, Kidoya H, Piccirillo R. Apelin Resistance Contributes to Muscle Loss during Cancer Cachexia in Mice. Cancers (Basel) 2022; 14:cancers14071814. [PMID: 35406586 PMCID: PMC8997437 DOI: 10.3390/cancers14071814] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/15/2022] [Accepted: 03/29/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Cancer cachexia is a highly debilitating syndrome involving severe body weight loss. Worldwide around 9–14.5 million cancer patients suffer from cachexia every year and many of them die because of cachexia. Our study aimed to assess the possible role of apelin against muscle loss during cancer growth given its beneficial effects against muscle atrophy during aging. We found apelin exhibiting advantageous effects against atrophy in in vitro models, but not in in vivo models, where we unraveled undesirable apelin resistance that may nullify apelin-based therapy for cancer cachexia. Abstract Cancer cachexia consists of dramatic body weight loss with rapid muscle depletion due to imbalanced protein homeostasis. We found that the mRNA levels of apelin decrease in muscles from cachectic hepatoma-bearing rats and three mouse models of cachexia. Furthermore, apelin expression inversely correlates with MuRF1 in muscle biopsies from cancer patients. To shed light on the possible role of apelin in cachexia in vivo, we generated apelin 13 carrying all the last 13 amino acids of apelin in D isomers, ultimately extending plasma stability. Notably, apelin D-peptides alter cAMP-based signaling in vitro as the L-peptides, supporting receptor binding. In vitro apelin 13 protects myotube diameter from dexamethasone-induced atrophy, restrains rates of degradation of long-lived proteins and MuRF1 expression, but fails to protect mice from atrophy. D-apelin 13 given intraperitoneally for 13 days in colon adenocarcinoma C26-bearing mice does not reduce catabolic pathways in muscles, as it does in vitro. Puzzlingly, the levels of circulating apelin seemingly deriving from cachexia-inducing tumors, increase in murine plasma during cachexia. Muscle electroporation of a plasmid expressing its receptor APJ, unlike apelin, preserves myofiber area from C26-induced atrophy, supporting apelin resistance in vivo. Altogether, we believe that during cachexia apelin resistance occurs, contributing to muscle wasting and nullifying any possible peptide-based treatment.
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Affiliation(s)
- Andrea David Re Cecconi
- Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy; (A.D.R.C.); (M.B.); (M.F.); (M.L.); (D.O.); (F.P.)
| | - Mara Barone
- Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy; (A.D.R.C.); (M.B.); (M.F.); (M.L.); (D.O.); (F.P.)
| | - Mara Forti
- Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy; (A.D.R.C.); (M.B.); (M.F.); (M.L.); (D.O.); (F.P.)
| | - Martina Lunardi
- Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy; (A.D.R.C.); (M.B.); (M.F.); (M.L.); (D.O.); (F.P.)
| | - Alfredo Cagnotto
- Molecular Biochemistry and Pharmacology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy; (A.C.); (M.S.)
| | - Mario Salmona
- Molecular Biochemistry and Pharmacology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy; (A.C.); (M.S.)
| | - Davide Olivari
- Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy; (A.D.R.C.); (M.B.); (M.F.); (M.L.); (D.O.); (F.P.)
| | - Lorena Zentilin
- Molecular Medicine, International Centre for Genetic Engineering and Biotechnology, Via Padriciano 99, 34149 Trieste, Italy;
| | - Andrea Resovi
- Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Stezzano 87, 24126 Bergamo, Italy; (A.R.); (P.P.); (D.B.)
| | - Perla Persichitti
- Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Stezzano 87, 24126 Bergamo, Italy; (A.R.); (P.P.); (D.B.)
| | - Dorina Belotti
- Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Stezzano 87, 24126 Bergamo, Italy; (A.R.); (P.P.); (D.B.)
| | - Federica Palo
- Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy; (A.D.R.C.); (M.B.); (M.F.); (M.L.); (D.O.); (F.P.)
| | - Nobuyuki Takakura
- Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka 565-0871, Japan;
| | - Hiroyasu Kidoya
- Department of Integrative Vascular Biology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui 910-1193, Japan;
| | - Rosanna Piccirillo
- Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy; (A.D.R.C.); (M.B.); (M.F.); (M.L.); (D.O.); (F.P.)
- Correspondence: ; Tel.: +39-02-39014371
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Yasir M, Senthilkumar GP, Jayashree K, Ramesh Babu K, Vadivelan M, Palanivel C. Association of serum omentin-1, apelin and chemerin concentrations with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients. Arch Physiol Biochem 2022; 128:313-320. [PMID: 31686535 DOI: 10.1080/13813455.2019.1680698] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Omentin-1 is a novel adipokine with anti-inflammatory functions. Apelin is associated with hyperinsulinemia and pathological angiogenesis. Chemerin has both pro- and anti-inflammatory actions and implicated in insulin resistance and metabolic syndrome. The aim of this study was to assess serum omentin-1, apelin and chemerin concentrations and to investigate their association with the presence and severity of DR in T2DM patients. Serum omentin-1, apelin and chemerin were measured in 112 patients with DR and 56 patients without DR. Bivariate analysis showed omentin-1 correlated negatively with hsCRP and TyG index; while apelin correlated positively with chemerin. Linear regression data showed that apelin and chemerin were independent predictors of DR severity. ROC curve revealed that omentin-1 was the best discriminant for DR while apelin was the best discriminant for vision threatening retinopathy. Serum omentin-1 concentration correlates negatively, while serum apelin and chemerin concentrations correlate positively with DR presence and severity in T2DM patients.
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Affiliation(s)
- Md Yasir
- Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
- Department of Biochemistry, North Eastern Indira Gandhi Regional Institute of Health & Medical Sciences (NEIGRIHMS), Shillong, India
| | | | - Kuppuswami Jayashree
- Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
| | - K Ramesh Babu
- Department of Ophthalmology, JIPMER, Puducherry, India
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Wang L, Zhu L. Exercise during pregnancy may have more benefits than we thought. EBioMedicine 2022; 77:103889. [PMID: 35193059 PMCID: PMC8866666 DOI: 10.1016/j.ebiom.2022.103889] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 02/06/2022] [Indexed: 11/25/2022] Open
Affiliation(s)
- Lingdi Wang
- Department of Physiology and Pathophysiology, Tianjin Key Laboratory of Cell Homeostasis and Major Diseases, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Lu Zhu
- Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
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Palmer ES, Irwin N, O’Harte FPM. Potential Therapeutic Role for Apelin and Related Peptides in Diabetes: An Update. Clin Med Insights Endocrinol Diabetes 2022; 15:11795514221074679. [PMID: 35177945 PMCID: PMC8844737 DOI: 10.1177/11795514221074679] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 01/04/2022] [Indexed: 01/10/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is an epidemic with an ever-increasing global prevalence. Current treatment strategies, although plentiful and somewhat effective, often fail to achieve desired glycaemic goals in many people, leading ultimately to disease complications. The lack of sustained efficacy of clinically-approved drugs has led to a heightened interest in the development of novel alternative efficacious antidiabetic therapies. One potential option in this regard is the peptide apelin, an adipokine that acts as an endogenous ligand of the APJ receptor. Apelin exists in various molecular isoforms and was initially studied for its cardiovascular benefits, however recent research suggests that it also plays a key role in glycaemic control. As such, apelin peptides have been shown to improve insulin sensitivity, glucose tolerance and lower circulating blood glucose. Nevertheless, native apelin has a short biological half-life that limits its therapeutic potential. More recently, analogues of apelin, particularly apelin-13, have been developed that possess a significantly extended biological half-life. These analogues may represent a promising target for future development of therapies for metabolic disease including diabetes and obesity.
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Affiliation(s)
- Ethan S Palmer
- Ethan S Palmer, Diabetes Research Group, Ulster University, Coleraine, Northern Ireland BT52 1SA, UK.
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Maternal exercise intergenerationally drives muscle-based thermogenesis via activation of apelin-AMPK signaling. EBioMedicine 2022; 76:103842. [PMID: 35081489 PMCID: PMC8790600 DOI: 10.1016/j.ebiom.2022.103842] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 01/11/2022] [Accepted: 01/12/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Sarcolipin and uncoupling protein 3 (UCP3) mediate muscle-based non-shivering thermogenesis (NST) to improve metabolic homeostasis. The impacts of maternal obesity (MO) and maternal exercise (ME) on NST in offspring muscle remain unexamined. METHODS Female mice were fed with a control diet or high fat diet to induce obesity. Then, obese mice were further separated into two groups: obesity only (OB) and OB plus daily exercise (OB/Ex). Fetal muscle was collected at embryonic day 18.5 and offspring mice at 3-month-old. Apelin administration during pregnancy and apelin receptor (APJ) knockout mouse were further used for investigating the mediatory role of APJ on muscle-based thermogenesis. To explore the direct effects of exercise on AMP-activated protein kinase (AMPK) downstream targets, AMPK knockout mouse was used. FINDINGS MO inhibited while ME activated AMPK and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in fetal muscle. AMPK activation increased sarcolipin expression, which inhibited the uptake of calcium ions into sarcoplasmic reticulum, thereby activating CaMKK2. Consistently, the expression of UCP3 and sarcolipin was suppressed due to MO but activated in ME fetal muscle. Importantly, changes of UCP3 and sarcolipin maintained in offspring muscle, showing the transgenerational effects. Furthermore, apelin administration during pregnancy mimicked the effects of ME on AMPK and CaMKK2 activation, and UCP3 and sarcolipin expression, underscoring the mediatory roles of apelin-AMPK signaling in improving fetal muscle development. INTERPRETATION ME, via activation of apelin signaling-AMPK axis, enhances NST gene expression in fetal and offspring muscle impaired due to MO, which intergenerationally protects offspring from diet-induced obesity and metabolic disorders. FUNDING This work was supported by National Institutes of Health Grant R01-HD067449.
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Abstract
CONTEXT Resistance exercise training has recently been considered as an effective type of training to increase energy metabolism and insulin sensitivity. However, mechanisms of the resistance training-induced improvements in energy metabolism and insulin sensitivity have not been fully understood. Zinc-α2-glycoprotein (ZAG), which is a novel adipokine, has beneficial effects on energy metabolism and insulin sensitivity. OBJECTIVE We investigated the effect of a single bout of resistance exercise on the ZAG concentration. METHODS Nine healthy men were enrolled. They performed a single bout of resistance exercise (bench press and leg press) consisting of 10 repetitions of five sets at 70% of maximum strength with 90-s rests in between sets. Blood samples were obtained before and after acute resistance exercise to measure the ZAG concentration. RESULTS The serum ZAG concentration significantly increased following acute resistance exercise. CONCLUSION This result suggests that a single bout of resistance exercise may enhance the ZAG concentration.
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Affiliation(s)
- Michihiro Kon
- School of International Liberal Studies, Chukyo University, Nagoya, Japan
- Department of Sports Sciences, Japan Institute of Sports Sciences, Tokyo, Japan
| | - Yasuhiro Suzuki
- Department of Sports Research, Japan Institute of Sports Sciences, Tokyo, Japan
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Shipl W, El Wakeel MS, Ahmad I, Mohammed M, Ali SO, El Wahab MA. Correlation of serum apelin level with carotid intima–media thickness and insulin resistance in a sample of Egyptian patients with type 2 diabetes mellitus. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2022; 27:13. [PMID: 35342448 PMCID: PMC8943574 DOI: 10.4103/jrms.jrms_675_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 05/22/2021] [Accepted: 09/01/2021] [Indexed: 11/19/2022]
Abstract
Background: Type 2 diabetes mellitus (T2DM) is a growing health problem in Egypt, with a significant impact on morbidity and mortality. Measurement of the carotid Intima-media thickness (CIMT) allows early detection of atherosclerotic blood vessel diseases. Apelin is an adipose tissue-derived hormone that may be associated with insulin resistance (IR). This study aimed to assess the level of serum apelin in patients with T2DM and its relation to IR and CIMT. Materials and Methods: A case-control study was conducted on 60 patients with T2DM and 30 healthy controls. T2DM was diagnosed based on American Diabetes Association criteria. The study was carried out at Al-Zahraa University Hospital, Cairo, Egypt, through the period from June to December 2019. The laboratory investigations included serum apelin and blood glucose hemostasis markers. CIMT was assessed using B-mode ultrasonography. Results: Patients’ group had a statistically significant higher apelin level than healthy controls (407.96 ± 291.07 versus 83.32 ± 10.55 ng/dL, P < 0.001). The correlation analysis showed that the serum apelin level correlated positively with glycemic indices, body weight, and waist circumference (P < 0.05). At cutoff value of >96 ng/dL, the serum apelin exhibited a sensitivity of 98.3% and specificity of 96.7%, positive predictive value of 98.1%, and negative predictive value of 96.5%, with a diagnostic accuracy of 95.1%. Serum apelin correlated positively with CIMT (r = 0.296, P = 0.022). Logistic regression analysis showed that systolic and diastolic blood pressures, Homeostasis Model Assessment of IR, and CIMT were independent predictors of serum apelin. Conclusion: Serum apelin may be correlated with the degree of carotid atherosclerosis and hence can be used as a prognostic biomarker.
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de Oliveira AA, Vergara A, Wang X, Vederas JC, Oudit GY. Apelin pathway in cardiovascular, kidney, and metabolic diseases: Therapeutic role of apelin analogs and apelin receptor agonists. Peptides 2022; 147:170697. [PMID: 34801627 DOI: 10.1016/j.peptides.2021.170697] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 11/12/2021] [Accepted: 11/15/2021] [Indexed: 02/07/2023]
Abstract
The apelin/apelin receptor (ApelinR) signal transduction pathway exerts essential biological roles, particularly in the cardiovascular system. Disturbances in the apelin/ApelinR axis are linked to vascular, heart, kidney, and metabolic disorders. Therefore, the apelinergic system has surfaced as a critical therapeutic strategy for cardiovascular diseases (including pulmonary arterial hypertension), kidney disease, insulin resistance, hyponatremia, preeclampsia, and erectile dysfunction. However, apelin peptides are susceptible to rapid degradation through endogenous peptidases, limiting their use as therapeutic tools and translational potential. These proteases include angiotensin converting enzyme 2, neutral endopeptidase, and kallikrein thereby linking the apelin pathway with other peptide systems. In this context, apelin analogs with enhanced proteolytic stability and synthetic ApelinR agonists emerged as promising pharmacological alternatives. In this review, we focus on discussing the putative roles of the apelin pathway in various physiological systems from function to dysfunction, and emphasizing the therapeutic potential of newly generated metabolically stable apelin analogs and non-peptide ApelinR agonists.
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Affiliation(s)
- Amanda A de Oliveira
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
| | - Ander Vergara
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
| | - Xiaopu Wang
- Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Physiology, University of Alberta, Edmonton, Alberta, Canada
| | - John C Vederas
- Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada
| | - Gavin Y Oudit
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
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Hao L, Bello NT. Reduced Body Fat and Epididymal Adipose Apelin Expression Associated With Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Weight Gain Prevention in High-Fat-Diet Fed Mice. Front Physiol 2021; 12:771816. [PMID: 34887778 PMCID: PMC8650585 DOI: 10.3389/fphys.2021.771816] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/19/2021] [Indexed: 11/18/2022] Open
Abstract
Raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] is a natural aromatic compound found in raspberries and other fruits. Raspberry ketone (RK) is synthetically produced for use as a commercial flavoring agent. In the United States and other markets, it is sold as a dietary supplement for weight control. The potential of RK to reduce or prevent excessive weight gain is unclear and could be a convergence of several different actions. This study sought to determine whether acute RK can immediately delay carbohydrate hyperglycemia and reduce gastrointestinal emptying. In addition, we explored the metabolic signature of chronic RK to prevent or remedy the metabolic effects of diet-induced weight gain. In high-fat diet (HFD; 45% fat)-fed male mice, acute oral gavage of RK (200 mg/kg) reduced hyperglycemia from oral sucrose load (4 g/kg) at 15 min. In HFD-fed female mice, acute oral RK resulted in an increase in blood glucose at 30 min. Chronic daily oral gavage of RK (200 mg/kg) commencing with HFD access (HFD_RK) for 11 weeks resulted in less body weight gain and reduced fat mass compared with vehicle treated (HFD_Veh) and chronic RK starting 4 weeks after HFD access (HFD_RKw4) groups. Compared with a control group fed a low-fat diet (LFD; 10% fat) and dosed with vehicle (LFD_Veh), glucose AUC of an oral glucose tolerance test was increased with HFD_Veh, but not in HFD_RK or HFD_RKw4. Apelin (Apln) gene expression in epididymal white adipose tissue was increased in HFD_Veh, but reduced to LFD_Veh levels in the HFD_RK group. Peroxisome proliferator activated receptor alpha (Ppara) gene expression was increased in the hepatic tissue of HFD_RK and HFD_RKw4 groups. Overall, our findings suggest that long term daily use of RK prevents diet-induced weight gain, normalizes high-fat diet-induced adipose Apln, and increases hepatic Ppara expression.
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Affiliation(s)
- Lihong Hao
- Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
| | - Nicholas T Bello
- Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
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Muroya S, Zhang Y, Kinoshita A, Otomaru K, Oshima K, Gotoh Y, Oshima I, Sano M, Roh S, Oe M, Ojima K, Gotoh T. Maternal Undernutrition during Pregnancy Alters Amino Acid Metabolism and Gene Expression Associated with Energy Metabolism and Angiogenesis in Fetal Calf Muscle. Metabolites 2021; 11:metabo11090582. [PMID: 34564398 PMCID: PMC8465837 DOI: 10.3390/metabo11090582] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/26/2021] [Accepted: 08/27/2021] [Indexed: 12/25/2022] Open
Abstract
To elucidate the mechanisms underlying maternal undernutrition (MUN)-induced fetal skeletal muscle growth impairment in cattle, the longissimus thoracis muscle of Japanese Black fetal calves at 8.5 months in utero was analyzed by an integrative approach with metabolomics and transcriptomics. The pregnant cows were fed on 60% (low-nutrition, LN) or 120% (high-nutrition, HN) of their overall nutritional requirement during gestation. MUN markedly decreased the bodyweight and muscle weight of the fetus. The levels of amino acids (AAs) and arginine-related metabolites including glutamine, gamma-aminobutyric acid (GABA), and putrescine were higher in the LN group than those in the HN group. Metabolite set enrichment analysis revealed that the highly different metabolites were associated with the metabolic pathways of pyrimidine, glutathione, and AAs such as arginine and glutamate, suggesting that MUN resulted in AA accumulation rather than protein accumulation. The mRNA expression levels of energy metabolism-associated genes, such as PRKAA1, ANGPTL4, APLNR, CPT1B, NOS2, NOS3, UCP2, and glycolytic genes were lower in the LN group than in the HN group. The gene ontology/pathway analysis revealed that the downregulated genes in the LN group were associated with glucose metabolism, angiogenesis, HIF-1 signaling, PI3K-Akt signaling, pentose phosphate, and insulin signaling pathways. Thus, MUN altered the levels of AAs and expression of genes associated with energy expenditure, glucose homeostasis, and angiogenesis in the fetal muscle.
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Affiliation(s)
- Susumu Muroya
- Division of Animal Products Research, NARO Institute of Livestock and Grassland Science (NILGS), Tsukuba 305-0901, Ibaraki, Japan; (M.O.); (K.O.)
- Correspondence: (S.M.); (T.G.)
| | - Yi Zhang
- Department of Agricultural Sciences and Natural Resources, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-8580, Japan; (Y.Z.); (A.K.); (I.O.)
| | - Aoi Kinoshita
- Department of Agricultural Sciences and Natural Resources, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-8580, Japan; (Y.Z.); (A.K.); (I.O.)
| | - Kounosuke Otomaru
- Joint Faculty of Veterinary Medicine, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-8580, Japan;
| | - Kazunaga Oshima
- Division of Year-Round Grazing Research, NARO Western Region Agricultural Research Center, 60 Yoshinaga, Ohda 694-0013, Shimane, Japan; (K.O.); (Y.G.)
| | - Yuji Gotoh
- Division of Year-Round Grazing Research, NARO Western Region Agricultural Research Center, 60 Yoshinaga, Ohda 694-0013, Shimane, Japan; (K.O.); (Y.G.)
| | - Ichiro Oshima
- Department of Agricultural Sciences and Natural Resources, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-8580, Japan; (Y.Z.); (A.K.); (I.O.)
| | - Mitsue Sano
- Faculty of Human Culture, University of Shiga Prefecture, 2500 Hassaka-cho, Hikone 522-8533, Shiga, Japan;
| | - Sanggun Roh
- Graduate School of Agricultural Science, Tohoku University, 468-1 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Miyagi, Japan;
| | - Mika Oe
- Division of Animal Products Research, NARO Institute of Livestock and Grassland Science (NILGS), Tsukuba 305-0901, Ibaraki, Japan; (M.O.); (K.O.)
| | - Koichi Ojima
- Division of Animal Products Research, NARO Institute of Livestock and Grassland Science (NILGS), Tsukuba 305-0901, Ibaraki, Japan; (M.O.); (K.O.)
| | - Takafumi Gotoh
- Department of Agricultural Sciences and Natural Resources, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-8580, Japan; (Y.Z.); (A.K.); (I.O.)
- Correspondence: (S.M.); (T.G.)
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Strutt B, Szlapinski S, Gnaneswaran T, Donegan S, Hill J, Bennett J, Hill DJ. Ontology of the apelinergic system in mouse pancreas during pregnancy and relationship with β-cell mass. Sci Rep 2021; 11:15475. [PMID: 34326390 PMCID: PMC8322410 DOI: 10.1038/s41598-021-94725-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Accepted: 07/15/2021] [Indexed: 02/07/2023] Open
Abstract
The apelin receptor (Aplnr) and its ligands, Apelin and Apela, contribute to metabolic control. The insulin resistance associated with pregnancy is accommodated by an expansion of pancreatic β-cell mass (BCM) and increased insulin secretion, involving the proliferation of insulin-expressing, glucose transporter 2-low (Ins+Glut2LO) progenitor cells. We examined changes in the apelinergic system during normal mouse pregnancy and in pregnancies complicated by glucose intolerance with reduced BCM. Expression of Aplnr, Apelin and Apela was quantified in Ins+Glut2LO cells isolated from mouse pancreata and found to be significantly higher than in mature β-cells by DNA microarray and qPCR. Apelin was localized to most β-cells by immunohistochemistry although Aplnr was predominantly associated with Ins+Glut2LO cells. Aplnr-staining cells increased three- to four-fold during pregnancy being maximal at gestational days (GD) 9-12 but were significantly reduced in glucose intolerant mice. Apelin-13 increased β-cell proliferation in isolated mouse islets and INS1E cells, but not glucose-stimulated insulin secretion. Glucose intolerant pregnant mice had significantly elevated serum Apelin levels at GD 9 associated with an increased presence of placental IL-6. Placental expression of the apelinergic axis remained unaltered, however. Results show that the apelinergic system is highly expressed in pancreatic β-cell progenitors and may contribute to β-cell proliferation in pregnancy.
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Affiliation(s)
- Brenda Strutt
- Lawson Health Research Institute, St Joseph Health Care, 268 Grosvenor St, London, ON, N6A 4V2, Canada
| | - Sandra Szlapinski
- Lawson Health Research Institute, St Joseph Health Care, 268 Grosvenor St, London, ON, N6A 4V2, Canada
- Department of Physiology and Pharmacology, Western University, London, ON, N6A 3K7, Canada
| | - Thineesha Gnaneswaran
- Department of Physiology and Pharmacology, Western University, London, ON, N6A 3K7, Canada
| | - Sarah Donegan
- Department of Physiology and Pharmacology, Western University, London, ON, N6A 3K7, Canada
| | - Jessica Hill
- Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW, UK
| | - Jamie Bennett
- Lawson Health Research Institute, St Joseph Health Care, 268 Grosvenor St, London, ON, N6A 4V2, Canada
- Life Sciences Program, School of Interdisciplinary Science, McMaster University, Hamilton, ON, L8S 4LD, Canada
| | - David J Hill
- Lawson Health Research Institute, St Joseph Health Care, 268 Grosvenor St, London, ON, N6A 4V2, Canada.
- Department of Physiology and Pharmacology, Western University, London, ON, N6A 3K7, Canada.
- Departments of Medicine and Paediatrics, Western University, London, ON, N6A 3K7, Canada.
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Luo J, Liu W, Feng F, Chen L. Apelin/APJ system: A novel therapeutic target for locomotor system diseases. Eur J Pharmacol 2021; 906:174286. [PMID: 34174264 DOI: 10.1016/j.ejphar.2021.174286] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 06/03/2021] [Accepted: 06/22/2021] [Indexed: 12/19/2022]
Abstract
Apelin is an endogenous ligand of G protein-coupled receptor APJ. Apelin/APJ system is widely expressed in abundant tissues, especially bone, joint and muscle tissue. This review focus on the effects of apelin/APJ system on locomotor system. An increasing number of evidence suggests that apelin/APJ system plays a crucial role in many physiological and pathological processes of locomotor system. Physiologically, apelin/APJ system promotes bone formation, muscle metabolism and skeletal muscle production. Pathologically, apelin/APJ system exacerbates osteoarthritis pathogenesis, whereas it alleviates osteoporosis. Besides, the level of apelin expression is regulated by different training modes, including continuous aerobic exercise, high-intensity interval training and resistance exercises. More importantly, exercise-induced apelin may be a potent pharmacological agent for the treatment of diseases and the regulation of physiological processes. Considering the pleiotropic effects of apelin on locomotor system, apelin/APJ system may be an important therapeutic target for locomotor system diseases.
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Affiliation(s)
- Jingshun Luo
- Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China
| | - Wei Liu
- Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Fen Feng
- School of Medicine, Shaoyang University, Shaoyang, 422000, China.
| | - Linxi Chen
- Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China.
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Castan-Laurell I, Dray C, Valet P. The therapeutic potentials of apelin in obesity-associated diseases. Mol Cell Endocrinol 2021; 529:111278. [PMID: 33838166 DOI: 10.1016/j.mce.2021.111278] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/26/2021] [Accepted: 04/02/2021] [Indexed: 01/23/2023]
Abstract
Apelin, a peptide with several active isoforms ranging from 36 to 12 amino acids and its receptor APJ, a G-protein-coupled receptor, are widely distributed. However, apelin has emerged as an adipokine more than fifteen years ago, integrating the field of inter-organs interactions. The apelin/APJ system plays important roles in several physiological functions both in rodent and humans such as fluid homeostasis, cardiovascular physiology, angiogenesis, energy metabolism. Thus the apelin/APJ system has generated great interest as a potential therapeutic target in different pathologies. The present review will consider the effects of apelin in metabolic diseases such as obesity and diabetes with a focus on diabetic cardiomyopathy among the complications associated with diabetes and APJ agonists or antagonists of interest in these diseases.
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Affiliation(s)
- I Castan-Laurell
- Restore UMR1301 Inserm, 5070 CNRS, Université Paul Sabatier, France.
| | - C Dray
- Restore UMR1301 Inserm, 5070 CNRS, Université Paul Sabatier, France
| | - P Valet
- Restore UMR1301 Inserm, 5070 CNRS, Université Paul Sabatier, France
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Abstract
CONTEXT Insulin resistance is the main triggering factor for type 2 diabetes. Recently, it has been reported that high-intensity sprint interval training (SIT) was effective for improving glucose metabolism and insulin sensitivity despite lower training volume. However, the mechanisms underlying the SIT-induced increases in glucose metabolism and insulin sensitivity have not been well-understood. Follistatin-like 1 (FSTL1) and apelin, which are novel myokines, have a favourable effect on glucose metabolism. OBJECTIVE We examined the impact of acute SIT on FSTL1 and apelin secretions. METHODS Eight healthy men were enrolled in this study. The subjects performed acute SIT consisting of four 30-s all-out cycling efforts with 4-min rest periods. Blood samples were obtained before and after the acute SIT to measure FSTL1 and apelin concentrations. RESULTS FSTL1 and apelin both significantly increased following acute SIT. CONCLUSION Acute SIT may be an effective stimulus for increasing of FSTL1 and apelin secretions.
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Affiliation(s)
- Michihiro Kon
- School of International Liberal Studies, Chukyo University, Nagoya, Japan
- Department of Sports Sciences, Japan Institute of Sports Sciences, Tokyo, Japan
| | - Yoshiko Ebi
- Department of Sports Sciences, Japan Institute of Sports Sciences, Tokyo, Japan
| | - Kohei Nakagaki
- Department of Sports Sciences, Japan Institute of Sports Sciences, Tokyo, Japan
- Department of Sports Sciences, Yamanashi Gakuin University, Kofu, Yamanashi, Japan
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Xu H, Wang Q, Wang Q, Che XQ, Liu X, Zhao S, Wang S. Clinical significance of apelin in the treatment of type 2 diabetic peripheral neuropathy. Medicine (Baltimore) 2021; 100:e25710. [PMID: 33907154 PMCID: PMC8084081 DOI: 10.1097/md.0000000000025710] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 03/16/2021] [Accepted: 04/08/2021] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. As apelin is an adipocytokine closely associated with diabetes, this study explored the clinical significance of serum apelin levels in patients with type 2 DPN before and after treatment. METHODS In total, 44 patients with T2DM without DPN (non-DPN group), 41 patients with DPN who received antihyperglycemic treatment (DPN-A group), 44 patients with DPN who received antihyperglycemic treatment combined with nutritional neurotherapy (DPN-B group), and 40 healthy control individuals (NC group) were selected continuously enrolled in the present study. Enzyme-linked immunosorbent assays (ELISA) were performed to determine serum levels of apelin and tumor necrosis factor-α (TNF-α). Related apelin, fasting blood glucose (FBG), glycosylated hemoglobin A1c, TNF-α, body mass index, fasting C peptide, and nerve conduction velocity (NCV) were recorded in each group before and after treatment. RESULTS Serum levels of apelin and TNF-α were higher in patients with diabetes than those in the NC group, as well as in the DPN group as compared to the non-DPN group; furthermore, some NCV values were significantly reduced in the DPN group. After treatment, the serum levels of apelin, TNF-α, and FBG reduced in patients with diabetes; moreover, apelin levels were found significantly lower in the DPN-B group as compared to the DPN-A group, while some NCV values significantly increased in the DPN-B group. Apelin was negatively correlated with part of NCV values and positively correlated with TNF-α and FBG (P < .01). CONCLUSION Our results show that the increase in serum apelin levels is an important clinical reference index for DPN, while a decrease indicates that the DPN treatment is effective.
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Affiliation(s)
- Hua Xu
- Department of Endocrinology
| | - Qi Wang
- Department of Pharmacy, The Fifth People's Hospital of Jinan
| | - Qian Wang
- Department of Ultrasound, Shandong Provincial Hospital, Jinan, Shandong Province, China
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Narayanan S, Wang S, Vasukuttan V, Vyas Devambatla RK, Dai D, Jin C, Snyder R, Laudermilk L, Runyon SP, Maitra R. Pyrazole Agonist of the Apelin Receptor Improves Symptoms of Metabolic Syndrome in Mice. J Med Chem 2021; 64:3006-3025. [PMID: 33705126 DOI: 10.1021/acs.jmedchem.0c01448] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Apelin receptor agonism improves symptoms of metabolic syndrome. However, endogenous apelin peptides have short half-lives, making their utility as potential drugs limited. Previously, we had identified a novel pyrazole-based agonist scaffold. Systematic modification of this scaffold was performed to produce compounds with improved ADME properties. Compound 13 with favorable agonist potency (cAMPi EC50 = 162 nM), human liver microsome stability (T1/2 = 62 min), and pharmacokinetic profile in rodents was identified. The compound was tested in a mouse model of diet-induced obesity (DIO) and metabolic syndrome for efficacy. Treatment with 13 led to significant weight loss, hypophagia, improved glucose utilization, reduced liver steatosis, and improvement of disease-associated biomarkers. In conclusion, a small-molecule agonist of the apelin receptor has been identified that is suitable for in vivo investigation of the apelinergic system in DIO and perhaps other diseases where this receptor has been implicated to play a role.
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Affiliation(s)
- Sanju Narayanan
- Center for Drug Discovery, RTI International, Research Triangle Park, Durham, North Carolina 27709, United States
| | - Shaobin Wang
- Center for Drug Discovery, RTI International, Research Triangle Park, Durham, North Carolina 27709, United States
| | - Vineetha Vasukuttan
- Center for Drug Discovery, RTI International, Research Triangle Park, Durham, North Carolina 27709, United States
| | | | - Donghua Dai
- Sterling Pharma Solutions Limited, Sheldon Drive, Cary, North Carolina 27513, United States
| | - Chunyang Jin
- Center for Drug Discovery, RTI International, Research Triangle Park, Durham, North Carolina 27709, United States
| | - Rodney Snyder
- Center for Drug Discovery, RTI International, Research Triangle Park, Durham, North Carolina 27709, United States
| | - Lucas Laudermilk
- Center for Drug Discovery, RTI International, Research Triangle Park, Durham, North Carolina 27709, United States
| | - Scott P Runyon
- Center for Drug Discovery, RTI International, Research Triangle Park, Durham, North Carolina 27709, United States
| | - Rangan Maitra
- Center for Drug Discovery, RTI International, Research Triangle Park, Durham, North Carolina 27709, United States
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Li H, Zhu H, Ge T, Wang Z, Zhang C. Mesenchymal Stem Cell-Based Therapy for Diabetes Mellitus: Enhancement Strategies and Future Perspectives. Stem Cell Rev Rep 2021; 17:1552-1569. [PMID: 33675006 DOI: 10.1007/s12015-021-10139-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2021] [Indexed: 12/11/2022]
Abstract
Diabetes mellitus (DM), a chronic disorder of carbohydrate metabolism, is characterized by the unbridled hyperglycemia resulted from the impaired ability of the body to either produce or respond to insulin. As a cell-based regenerative therapy, mesenchymal stem cells (MSCs) hold immense potency for curing DM duo to their easy isolation, multi-differentiation potential, and immunomodulatory property. However, despite the promising efficacy in pre-clinical animal models, naive MSC administration fails to exhibit clinically satisfactory therapeutic outcomes, which varies greatly among individuals with DM. Recently, numbers of innovative strategies have been applied to improve MSC-based therapy. Preconditioning, genetic modification, combination therapy and exosome application are representative strategies to maximize the therapeutic benefits of MSCs. Therefore, in this review, we summarize recent advancements in mechanistic studies of MSCs-based treatment for DM, and mainly focus on the novel approaches aiming to improve the anti-diabetic potentials of naive MSCs. Additionally, the potential directions of MSCs-based therapy for DM are also proposed at a glance.
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Affiliation(s)
- Haisen Li
- Department of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China.,Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.,Sinoneural Cell Engineering Group Holdings Co., Ltd., Shanghai 201100, China
| | - Hao Zhu
- Sinoneural Cell Engineering Group Holdings Co., Ltd., Shanghai 201100, China
| | - Ting Ge
- Xinxiang First People's Hospital, Xinxiang 453000, China
| | - Zhifeng Wang
- Department of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China. .,Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. .,Sinoneural Cell Engineering Group Holdings Co., Ltd., Shanghai 201100, China.
| | - Chao Zhang
- Department of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China. .,Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
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Hu G, Wang Z, Zhang R, Sun W, Chen X. The Role of Apelin/Apelin Receptor in Energy Metabolism and Water Homeostasis: A Comprehensive Narrative Review. Front Physiol 2021; 12:632886. [PMID: 33679444 PMCID: PMC7928310 DOI: 10.3389/fphys.2021.632886] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 01/21/2021] [Indexed: 11/13/2022] Open
Abstract
The apelin receptor (APJ) is a member of the family A of G-protein-coupled receptors (GPCRs) and is involved in range of physiological and pathological functions, including fluid homeostasis, anxiety, and depression, as well as cardiovascular and metabolic disorders. APJ was classically described as a monomeric transmembrane receptor that forms a ternary complex together with its ligand and associated G proteins. More recently, increasing evidence indicates that APJ may interact with other GPCRs to form heterodimers, which may selectively modulate distinct intracellular signal transduction pathways. Besides, the apelin/APJ system plays important roles in the physiology and pathophysiology of several organs, including regulation of blood pressure, cardiac contractility, angiogenesis, metabolic balance, and cell proliferation, apoptosis, or inflammation. Additionally, the apelin/APJ system is widely expressed in the central nervous system, especially in neurons and oligodendrocytes. This article reviews the role of apelin/APJ in energy metabolism and water homeostasis. Compared with the traditional diuretics, apelin exerts a positive inotropic effect on the heart, while increases water excretion. Therefore, drugs targeting apelin/APJ system undoubtedly provide more therapeutic options for patients with congestive heart failure accompanied with hyponatremia. To provide more precise guidance for the development of clinical drugs, further in-depth studies are warranted on the metabolism and signaling pathways associated with apelin/APJ system.
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Affiliation(s)
- Gonghui Hu
- Department of Physiology, Shandong First Medical University (Shandong Academy of Medical Sciences), Taian, China
| | - Zhen Wang
- Neurobiology Institute, Jining Medical University, Jining, China
| | - Rumin Zhang
- Neurobiology Institute, Jining Medical University, Jining, China
| | - Wenping Sun
- Department of Pathology, Shandong First Medical University (Shandong Academy of Medical Sciences), Taian, China
| | - Xiaoyu Chen
- Department of Physiology, Shandong First Medical University (Shandong Academy of Medical Sciences), Taian, China
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Estienne A, Bongrani A, Froment P, Dupont J. Apelin and chemerin receptors are G protein-coupled receptors involved in metabolic as well as reproductive functions: Potential therapeutic implications? ACTA ACUST UNITED AC 2021. [DOI: 10.1016/j.coemr.2020.09.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Darvishi S, Rafraf M, Asghari-Jafarabadi M, Farzadi L. Synbiotic Supplementation Improves Metabolic Factors and Obesity Values in Women with Polycystic Ovary Syndrome Independent of Affecting Apelin Levels: A Randomized Double-Blind Placebo - Controlled Clinical Trial. INTERNATIONAL JOURNAL OF FERTILITY & STERILITY 2021; 15:51-59. [PMID: 33497048 PMCID: PMC7838763 DOI: 10.22074/ijfs.2021.6186] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Accepted: 09/25/2020] [Indexed: 12/13/2022]
Abstract
Background This research investigated the symbiotic supplement influences on serum glycemic indices and lipids as well as apelin rates and obesity values in polycystic ovary syndrome (PCOS) patients. Materials and Methods A total of 68 obese or overweight patients (20-44 years old) with PCOS were enrolled to conduct a randomized double-blinded placebo-controlled clinical trial. A total of 34 people in the synbiotic group received a synbiotic supplement and 34 people in the placebo group received placebo, daily for 8 weeks. Fasting blood specimens, anthropometric measurements and dietary intake data were gathered three times during the study. The information was analyzed by independent t test, paired t test, analysis of covariance and chi-square test. Results Synbiotic supplementation significantly decreased serum fasting glucose (P=0.02), insulin (P=0.001), homeostatic model assessment for insulin resistance (IR, P=0.001), weight (P=0.02), body mass index (BMI, P=0.02), waist circumference (WC, P=0.01), hip circumference (HC, P=0.02), and waist-to-height ratio (WHtR, P=0.02) but significantly increased high-density lipoprotein (HDL) cholesterol (P=0.02) compared to the placebo. At the end of the trial, no significant differences were seen in serum total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, or apelin levels as well as waist-to-hip ratio (WHR) between the two groups. Conclusion Synbiotic supplementation improved glycemic indices, lipid profile and obesity values in women with PCOS. These beneficial effects were not related with alterations in serum apelin levels (Registration number: IRCT20100408003664N19).
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Affiliation(s)
- Sima Darvishi
- Student's Research Committee, Department of Community Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Rafraf
- Nutrition Research Center, Department of Community Nutrition, Faculty of Nutrition and Food Science, 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
| | - Laya Farzadi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Saeidi A, Haghighi MM, Kolahdouzi S, Daraei A, Abderrahmane AB, Essop MF, Laher I, Hackney AC, Zouhal H. The effects of physical activity on adipokines in individuals with overweight/obesity across the lifespan: A narrative review. Obes Rev 2021; 22:e13090. [PMID: 32662238 DOI: 10.1111/obr.13090] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 06/05/2020] [Accepted: 06/12/2020] [Indexed: 12/14/2022]
Abstract
This narrative review summarizes current knowledge on the effects of physical activity (PA) on adipokine levels in individuals with overweight and obesity. Approximately 90 investigations including randomized control, cross-sectional and longitudinal studies that reported on the effects of a single session of PA (acute) or long-term PA (chronic) on adipokine levels in individuals with overweight/obesity were reviewed. The findings support the notion that there is consensus on the benefits of chronic exercise training-regardless of the mode (resistance vs. aerobic), intensity and cohort (healthy vs. diabetes)-on adipokine levels (such as tumour necrosis factor-alpha, interleukin-6, adiponectin, visfatin, omentin-1 and leptin). However, several confounding factors (frequency, intensity, time and type of exercise) can alter the magnitude of the effects of an acute exercise session. Available evidence suggests that PA, as a part of routine lifestyle behaviour, improves obesity complications by modulating adipokine levels. However, additional research is needed to help identify the most effective interventions to elicit the most beneficial changes in adipokine levels in individuals with overweight/obesity.
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Affiliation(s)
- Ayoub Saeidi
- Department of Physical Education, Damghan Branch, Islamic Azad University, Damghan, Iran
| | - Marjan Mosalman Haghighi
- Faculty of Medicine and Health, Cardiology Centre, The University of Sydney, The Children's Hospital at Westmead, Sydney, Australia
| | - Sarkawt Kolahdouzi
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Iran
| | - Ali Daraei
- Department of Biological Sciences in Sport, Faculty of Sports Sciences and Health, Shahid Beheshti University, Tehran, Iran
| | | | - M Faadiel Essop
- Centre for Cardio-metabolic Research in Africa (CARMA), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Ismail Laher
- Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, Canada
| | - Anthony C Hackney
- Department of Exercise and Sport Science, University of North Carolina, Chapel Hill, NC, USA
| | - Hassane Zouhal
- Movement, Sport and Health Sciences Laboratory (M2S), UFR-STAPS, University of Rennes 2-ENS Rennes, Rennes, France
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