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Almpanidou S, Vachliotis ID, Goulas A, Polyzos SA. The potential role of adipokines and hepatokines in age-related ocular diseases. Metabol Open 2025; 26:100365. [PMID: 40330313 PMCID: PMC12053655 DOI: 10.1016/j.metop.2025.100365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 04/02/2025] [Accepted: 04/14/2025] [Indexed: 05/08/2025] Open
Abstract
Age-related ocular diseases, including diabetic retinopathy (DR), age-related macular degeneration (AMD), cataract and glaucoma may lead to visual impairment and even to blindness. Metabolic diseases, such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as potential risk factors of age-related ocular diseases, especially DR. Visceral adiposity has been associated with increased risk of DR and AMD in most clinical studies, although body mass index has to-date provided conflicting association with DR and AMD. In addition, obesity is recognized as a risk factor of cataract and glaucoma. Similarly to obesity, MASLD appears to be associated with DR in patients with type 1 diabetes mellitus, but probably not in those with type 2 diabetes mellitus. A potential positive association between MASLD and AMD, glaucoma and cataract is supported by limited evidence to-date, thus needing further investigation. Altered secretion patterns of adipokines (adiponectin, leptin, lipocalin-2, resistin) and hepatokines [adropin, fetuin-A, fibroblast growth factor (FGF)-21, retinol binding protein (RBP)-4] seem to disrupt ocular homeostasis and contribute to the development of age-related ocular diseases in the context of obesity and MASLD. In this regard, novel adipokine-based and hepatokine-based therapies may be added to the treatment options for ocular diseases in the future. This narrative review aimed to summarize evidence on the interconnection of obesity and MASLD with age-related ocular diseases, with a specific focus on the roles of adipokines and hepatokines as mediators of these potential associations.
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Affiliation(s)
- Stavroula Almpanidou
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ilias D. Vachliotis
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Antonis Goulas
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stergios A. Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Luo YY, Ba XY, Wang L, Zhang YP, Xu H, Chen PQ, Zhang LB, Han J, Luo H. LEF1 influences diabetic retinopathy and retinal pigment epithelial cell ferroptosis via the miR-495-3p/GRP78 axis through lnc-MGC. World J Diabetes 2025; 16:92003. [PMID: 40093269 PMCID: PMC11885969 DOI: 10.4239/wjd.v16.i3.92003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 11/10/2024] [Accepted: 12/11/2024] [Indexed: 01/21/2025] Open
Abstract
BACKGROUND Diabetic retinopathy (DR) is one of the major eye diseases contributing to blindness worldwide. Endoplasmic reticulum (ER) stress in retinal cells is a key factor leading to retinal inflammation and vascular leakage in DR, but its mechanism is still unclear. AIM To investigate the potential mechanism of LEF1 and related RNAs in DR. METHODS ARPE-19 cells were exposed to high levels of glucose for 24 hours to simulate a diabetic environment. Intraperitoneally injected streptozotocin was used to induce the rat model of DR. The expression levels of genes and related proteins were measured by RT-qPCR and Western blotting; lnc-MGC and miR-495-3p were detected by fluorescent in situ hybridization; CCK-8 and TUNEL assays were used to detect cell viability and apoptosis; enzyme-linked immunosorbent assay was used to detect inflammatory factors; dual-luciferase gene assays were used to verify the targeting relationship; and the retina was observed by HE staining. RESULTS LEF1 and lnc-MGC have binding sites, and lnc-MGC can regulate the miR-495-3p/GRP78 molecular axis. In high glucose-treated cells, inflammation was aggravated, the intracellular reactive oxygen species concentration was increased, cell viability was reduced, apoptosis was increased, the ER response was intensified, and ferroptosis was increased. As an ER molecular chaperone, GRP78 regulates the ER and ferroptosis under the targeting of miR-495-3p, whereas inhibiting LEF1 can further downregulate the expression of lnc-MGC, increase the level of miR-495-3p, and sequentially regulate the level of GRP78 to alleviate the occurrence and development of DR. Animal experiments indicated that the knockdown of LEF1 can affect the lnc-MGC/miR-495-3p/GRP78 signaling axis to restrain the progression of DR. CONCLUSION LEF1 knockdown can regulate the miR-495-3p/GRP78 molecular axis through lnc-MGC, which affects ER stress and restrains the progression of DR and ferroptosis in retinal pigment epithelial cells.
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Affiliation(s)
- Yi-Yi Luo
- Precision Medicine Center of Chuxiong Yi Autonomous Prefecture, The People's Hospital of Chuxiong Yi Autonomous Prefecture & The Fourth Affiliated Hospital of DaLi University, Chuxiong 675000, Yunnan Province, China
| | - Xue-Ying Ba
- Precision Medicine Center of Chuxiong Yi Autonomous Prefecture, The People's Hospital of Chuxiong Yi Autonomous Prefecture & The Fourth Affiliated Hospital of DaLi University, Chuxiong 675000, Yunnan Province, China
| | - Ling Wang
- Department of Endocrinology, The People's Hospital of Chuxiong Yi Autonomous Prefecture & The Fourth Affiliated Hospital of DaLi University, Chuxiong 675000, Yunnan Province, China
| | - Ye-Pin Zhang
- Department of Pathology, The People's Hospital of Chuxiong Yi Autonomous Prefecture & The Fourth Affiliated Hospital of DaLi University, Chuxiong 675000, Yunnan Province, China
| | - Hong Xu
- Department of Ophthalmology, The People's Hospital of Chuxiong Yi Autonomous Prefecture & The Fourth Affiliated Hospital of DaLi University, Chuxiong 675000, Yunnan Province, China
| | - Pei-Qi Chen
- Department of Endocrinology, The People's Hospital of Chuxiong Yi Autonomous Prefecture & The Fourth Affiliated Hospital of DaLi University, Chuxiong 675000, Yunnan Province, China
| | - Li-Bo Zhang
- Department of Ophthalmology, The People's Hospital of Chuxiong Yi Autonomous Prefecture & The Fourth Affiliated Hospital of DaLi University, Chuxiong 675000, Yunnan Province, China
| | - Jian Han
- Precision Medicine Center of Chuxiong Yi Autonomous Prefecture, The People's Hospital of Chuxiong Yi Autonomous Prefecture & The Fourth Affiliated Hospital of DaLi University, Chuxiong 675000, Yunnan Province, China
| | - Heng Luo
- Precision Medicine Center of Chuxiong Yi Autonomous Prefecture, The People's Hospital of Chuxiong Yi Autonomous Prefecture & The Fourth Affiliated Hospital of DaLi University, Chuxiong 675000, Yunnan Province, China
- Department of Ophthalmology, The People's Hospital of Chuxiong Yi Autonomous Prefecture & The Fourth Affiliated Hospital of DaLi University, Chuxiong 675000, Yunnan Province, China
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Hasanpour-Segherlou Z, Butler AA, Candelario-Jalil E, Hoh BL. Role of the Unique Secreted Peptide Adropin in Various Physiological and Disease States. Biomolecules 2024; 14:1613. [PMID: 39766320 PMCID: PMC11674490 DOI: 10.3390/biom14121613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 12/09/2024] [Accepted: 12/13/2024] [Indexed: 01/11/2025] Open
Abstract
Adropin, a secreted peptide hormone identified in 2008, plays a significant role in regulating energy homeostasis, glucose metabolism, and lipid metabolism. Its expression is linked to dietary macronutrient intake and is influenced by metabolic syndrome, obesity, diabetes, and cardiovascular diseases. Emerging evidence suggests that adropin might be a biomarker for various conditions, including metabolic syndrome, coronary artery disease, and hypertensive disorders complicating pregnancy. In cerebrovascular diseases, adropin demonstrates protective effects by reducing blood-brain barrier permeability, brain edema, and infarct size while improving cognitive and sensorimotor functions in ischemic stroke models. The protective effects of adropin extend to preventing endothelial damage, promoting angiogenesis, and mitigating inflammation, making it a promising therapeutic target for cardiovascular and neurodegenerative diseases. This review provides a comprehensive overview of adropin's multifaceted roles in physiological and pathological conditions, as well as our recent work demonstrating adropin's role in subarachnoid hemorrhage-mediated neural injury and delayed cerebral infarction.
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Affiliation(s)
| | - Andrew A. Butler
- Department of Pharmacology and Physiological Sciences, Saint Louis University, Saint Louis, MO 63104, USA;
| | - Eduardo Candelario-Jalil
- Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA;
| | - Brian L. Hoh
- Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, FL 32610, USA;
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Aydin S, Kilinc F, Ugur K, Aydin MA, Yalcin MH, Kuloglu T, Kaya Tektemur N, Albayrak S, Emre E, Yardim M, Akkoc RF, Hancer S, Sahin İ, Cinar V, Akbulut T, Demircan S, Evren B, Gencer BT, Aksoy A, Yilmaz Bozoglan M, Aydemir İ, Aydin S. Effects of irisin and exercise on adropin and betatrophin in a new metabolic syndrome model. Biotech Histochem 2024; 99:21-32. [PMID: 37933453 DOI: 10.1080/10520295.2023.2276205] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2023] Open
Abstract
Metabolic syndrome (MetS) is a prevalent public health problem. Uric acid (UA) is increased by MetS. We investigated whether administration of UA and 10% fructose (F) would accelerate MetS formation and we also determined the effects of irisin and exercise. We used seven groups of rats. Group 1 (control); group 2 (sham); group 3 (10% F); group 4 (1% UA); group 5 (2% UA); group 6 (10% F + 1% UA); and Group 7, (10% F + 2% UA). After induction of MetS (groups 3 -7), Group 3 was divided into three subgroups: 3A, no further treatment; 3B, irisin treatment; 3C, irisin treatment + exercise. Group 4, 1% UA, which was divided into three subgroups: 4A, no further treatment; 4B, irisin treatment; 4C, Irisin treatment + exercise. Group 5, 2% UA, which was divided into three subgroups: 5A, no further treatment; 5B, irisin treatment; 5C, irisin treatment + exercise. Group 6, 10% F + 1% UA, which was divided into three subgroups: 6A, no further treatment; 6B, irisin treatment; 6C, irisin treatment + exercise. Group 7, 10% F + 2% UA, which was divided into three subgroups: 7A, no further treatment; 7B, irisin treatment; 7C, irisin treatment + exercise., İrisin was administered 10 ng/kg irisin intraperitoneally on Monday, Wednesday, Friday, Sunday each week for 1 month. The exercise animals (in addition to irisin treatment) also were run on a treadmill for 45 min on Monday, Wednesday, Friday, Sunday each week for 1 month. The rats were sacrificed and samples of liver, heart, kidney, pancreas, skeletal muscles and blood were obtained. The amounts of adropin (ADR) and betatrophin in the tissue supernatant and blood were measured using an ELISA method. Immunohistochemistry was used to detect ADR and betatrophin expression in situ in tissue samples. The duration of these experiments varied from 3 and 10 weeks. The order of development of MetS was: group 7, 3 weeks; group 6, 4 weeks; group 5, 6 weeks; group 4, 7 weeks; group 3, 10 weeks. Kidney, liver, heart, pancreas and skeletal muscle tissues are sources of adropin and betatrophin. In these tissues and in the circulation, adropin was decreased significantly, while betatrophin was increased significantly due to MetS; irisin + exercise reversed this situation. We found that the best method for creating a MetS model was F + UA2 supplementation. Our method is rapid and simple. Irisin + exercise was best for preventing MetS.
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Affiliation(s)
- Suna Aydin
- Department of Cardiovascular Surgery, Fethi Sekin City Hospital, Elazig, Turkiye
- Department of Anatomy, School of Medicine, Firat University, Elazig, Turkiye
- Department of Histology and Embryology, School of Veterinary Medicine, Firat University, Elazig, Turkiye
| | - Faruk Kilinc
- Department of Internal Medicine (Endocrinology and Metabolism Diseases), School of Medicine, Firat University, Elazig, Turkiye
| | - Kader Ugur
- Department of Internal Medicine (Endocrinology and Metabolism Diseases), School of Medicine, Firat University, Elazig, Turkiye
| | | | - Mehmet Hanifi Yalcin
- Department of Histology and Embryology, School of Veterinary Medicine, Firat University, Elazig, Turkiye
| | - Tuncay Kuloglu
- Department of Histology and Embryology, School of Medicine, Firat University, Elazig, Turkiye
| | - Nalan Kaya Tektemur
- Department of Histology and Embryology, School of Medicine, Firat University, Elazig, Turkiye
| | - Serdal Albayrak
- Department of Brain and Nerve Surgery, Elazig Fethi Sekin City Hospital, Elazig, Turkiye
| | - Elif Emre
- Department of Anatomy, School of Medicine, Firat University, Elazig, Turkiye
| | - Meltem Yardim
- Department of Medical Biochemistry, Faculty of Sport Sciences, Yerkoy State Hospital, Yozgat, Turkiye
| | - Ramazan Fazil Akkoc
- Department of Anatomy, School of Medicine, Firat University, Elazig, Turkiye
| | - Serhat Hancer
- Department of Histology and Embryology, School of Medicine, Firat University, Elazig, Turkiye
| | - İbrahim Sahin
- Department of Medical Biochemistry and Clinical Biochemistry, Firat Hormones Research Group, Medical School, Firat University, Elazig, Turkiye
- Department of Medical Biology, Medical School, Erzincan Binali Yildirim University, Erzincan, Turkiye
| | - Vedat Cinar
- Department of Physical Education and Sports Teaching, Faculty of Sport Sciences, Firat University, Elazig, Turkey
| | - Taner Akbulut
- Department of Sports and Health, Faculty of Sport Sciences, Firat University, Elazig, Turkiye
| | - Selcuk Demircan
- Department of Intensive Care, Inonu University Hospital, Malatya, Turkiye
| | - Bahri Evren
- Department of Internal Medicine, School of Medicine, Inonu University, Malatya, Turkiye
| | - Berrin Tarakci Gencer
- Department of Histology and Embryology, School of Veterinary Medicine, Firat University, Elazig, Turkiye
| | - Aziz Aksoy
- Nature and Engineering Faculty, Malatya Turgut Ozal University, Malatya, Turkiye
| | - Merve Yilmaz Bozoglan
- Department of Medical Pharmacology, Medical School, Firat University, Elazig, Turkiye
| | - İsa Aydemir
- Department of Physical Education and Sports Teaching, Faculty of Sport Sciences, Firat University, Elazig, Turkey
| | - Suleyman Aydin
- Department of Medical Biochemistry and Clinical Biochemistry, Firat Hormones Research Group, Medical School, Firat University, Elazig, Turkiye
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Ali II, D'Souza C, Tariq S, Adeghate EA. Adropin Is Expressed in Pancreatic Islet Cells and Reduces Glucagon Release in Diabetes Mellitus. Int J Mol Sci 2024; 25:9824. [PMID: 39337311 PMCID: PMC11432804 DOI: 10.3390/ijms25189824] [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: 07/22/2024] [Revised: 08/30/2024] [Accepted: 09/06/2024] [Indexed: 09/30/2024] Open
Abstract
Diabetes mellitus affects 537 million adults around the world. Adropin is expressed in different cell types. Our aim was to investigate the cellular localization in the endocrine pancreas and its effect on modulating pancreatic endocrine hormone release in streptozotocin (STZ)-induced diabetic rats. Adropin expression in the pancreas was investigated in normal and diabetic rats using immunohistochemistry and immunoelectron microscopy. Serum levels of insulin, glucagon pancreatic polypeptide (PP), and somatostatin were measured using a Luminex® χMAP (Magpix®) analyzer. Pancreatic endocrine hormone levels in INS-1 832/3 rat insulinoma cells, as well as pancreatic tissue fragments of normal and diabetic rats treated with different concentrations of adropin (10-6, 10-9, and 10-12 M), were measured using ELISA. Adropin was colocalized with cells producing either insulin, glucagon, or PP. Adropin treatment reduced the number of glucagon-secreting alpha cells and suppressed glucagon release from the pancreas. The serum levels of GLP-1 and amylin were significantly increased after treatment with adropin. Our study indicates a potential role of adropin in modulating glucagon secretion in animal models of diabetes mellitus.
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Affiliation(s)
- Ifrah I Ali
- Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - Crystal D'Souza
- Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - Saeed Tariq
- Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
| | - Ernest A Adeghate
- Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
- Zayed Foundation, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates
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Wang J, Song X, Xia Z, Feng S, Zhang H, Xu C, Zhang H. Serum biomarkers for predicting microvascular complications of diabetes mellitus. Expert Rev Mol Diagn 2024; 24:703-713. [PMID: 39158206 DOI: 10.1080/14737159.2024.2391021] [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: 02/27/2024] [Accepted: 08/06/2024] [Indexed: 08/20/2024]
Abstract
INTRODUCTION Diabetic microvascular complications such as retinopathy, nephropathy, and neuropathy are primary causes of blindness, terminal renal failure, and neuropathic disorders in type 2 diabetes mellitus patients. Identifying reliable biomarkers promptly is pivotal for early detection and intervention in these severe complications. AREAS COVERED This review offers a thorough examination of the latest research concerning serum biomarkers for the prediction and assessment of diabetic microvascular complications. It encompasses biomarkers associated with glycation, oxidative stress, inflammation, endothelial dysfunction, basement membrane thickening, angiogenesis, and thrombosis. The review also highlights the potential of emerging biomarkers, such as microRNAs and long non-coding RNAs. EXPERT OPINION Serum biomarkers are emerging as valuable tools for the early assessment and therapeutic guidance of diabetic microvascular complications. The biomarkers identified not only reflect the underlying pathophysiology but also align with the extent of the disease. However, further validation across diverse populations and improvement of the practicality of these biomarkers in routine clinical practice are necessary. Pursuing these objectives is essential to advance early diagnosis, risk assessment, and individualized treatment regimens for those affected by diabetes.
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Affiliation(s)
- Jiajia Wang
- Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Department of Laboratory Medicine, Sichuan Provincial People's Hospital Chuandong Hospital ＆ Dazhou First People's Hospital, Dazhou, China
| | - Xiaoyi Song
- School of medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ziqiao Xia
- Laboratory medicine, Qianwei People's Hospital, Leshan, Sichuan, China
| | - Shu Feng
- Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Hangfeng Zhang
- Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Chengjie Xu
- Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Hui Zhang
- Department of Ultrasound, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
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Wu J, Duan C, Yang Y, Wang Z, Tan C, Han C, Hou X. Insights into the liver-eyes connections, from epidemiological, mechanical studies to clinical translation. J Transl Med 2023; 21:712. [PMID: 37817192 PMCID: PMC10566185 DOI: 10.1186/s12967-023-04543-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 09/19/2023] [Indexed: 10/12/2023] Open
Abstract
Maintenance of internal homeostasis is a sophisticated process, during which almost all organs get involved. Liver plays a central role in metabolism and involves in endocrine, immunity, detoxification and storage, and therefore it communicates with distant organs through such mechanisms to regulate pathophysiological processes. Dysfunctional liver is often accompanied by pathological phenotypes of distant organs, including the eyes. Many reviews have focused on crosstalk between the liver and gut, the liver and brain, the liver and heart, the liver and kidney, but with no attention paid to the liver and eyes. In this review, we summarized intimate connections between the liver and the eyes from three aspects. Epidemiologically, we suggest liver-related, potential, protective and risk factors for typical eye disease as well as eye indicators connected with liver status. For molecular mechanism aspect, we elaborate their inter-organ crosstalk from metabolism (glucose, lipid, proteins, vitamin, and mineral), detoxification (ammonia and bilirubin), and immunity (complement and inflammation regulation) aspect. In clinical application part, we emphasize the latest advances in utilizing the liver-eye axis in disease diagnosis and therapy, involving artificial intelligence-deep learning-based novel diagnostic tools for detecting liver disease and adeno-associated viral vector-based gene therapy method for curing blinding eye disease. We aim to focus on and provide novel insights into liver and eyes communications and help resolve existed clinically significant issues.
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Affiliation(s)
- Junhao Wu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
| | - Caihan Duan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
| | - Yuanfan Yang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Zhe Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
| | - Chen Tan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
| | - Chaoqun Han
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei China
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Chang X, Jin F, Wang L, Jiang Y, Wang P, Liu J, Zhao L. Adropin - A new player in energy regulation predicts long-term prognosis of patients with acute myocardial infarction. Heliyon 2023; 9:e17803. [PMID: 37455994 PMCID: PMC10344749 DOI: 10.1016/j.heliyon.2023.e17803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 06/15/2023] [Accepted: 06/28/2023] [Indexed: 07/18/2023] Open
Abstract
Background As a novel energy homeostasis regulator, Adropin not only plays a vital part in meditating energy metabolism, but also has a certain correlation with atherosclerotic diseases. The purpose of this study was to evaluate the effect of Adropin on the long-term prognosis of patients with acute myocardial infarction (AMI). Methods 162 recruited patients with AMI were divided into low Adropin group (Adropin<166.3 pg/mL, n = 82) and high Adropin group (Adropin≥166.3 pg/mL, n = 80), according to the mean value of serum Adropin level. Patients were followed up and major adverse cardiac events (MACEs) were recorded. The Kaplan-Meier method and Cox regression model were used to evaluate the survival of patients and the related factors of cardiac events. Results Diabetes was more common in low Adropin group than that in high Adropin group (P < 0.05). Patients were followed up for an average of 50.3 ± 19.2 months. MACEs occurred in 37 patients (22.8%), including 6 cardiac deaths (3.7%), 14 recurrent myocardial infarction (8.6%) and 17 rehospitalization of heart failure (10.5%). The incidence of recurrent myocardial infarction in low Adropin group was higher than that in high Adropin group (13.4% vs 3.8%, P < 0.05). There was no significant difference in the overall incidence of MACE, cardiac death and rehospitalization of heart failure between the two groups. Kaplan-Meier method (log rank test) analysis results showed that patients with low Adropin had lower survival rate without recurrent myocardial infarction (log rank P = 0.035). Conclusion Low Adropin level was associated with an increased risk of long-term recurrent myocardial infarction in patients with AMI.
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Affiliation(s)
- Xiansong Chang
- Emergency Department of Xuguan District, The Second Affiliated Hospital of Soochow University, China
- Department of Cardiology, The Second Affiliated Hospital of Soochow University, China
| | - Fulu Jin
- Department of Cardiology, The Second Affiliated Hospital of Soochow University, China
| | - Li Wang
- Emergency Department of Xuguan District, The Second Affiliated Hospital of Soochow University, China
| | - Yufeng Jiang
- Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital, China
| | - Peiyu Wang
- Department of Cardiology, The Second Affiliated Hospital of Soochow University, China
| | - Junyan Liu
- High-tech Zone (Huqiu District) Hushuguan Town Community Health Service Center of Suzhou, China
| | - Liangping Zhao
- Department of Cardiology, The Second Affiliated Hospital of Soochow University, China
- Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital, China
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Violetta L, Kartasasmita AS, Supriyadi R, Rita C. Circulating Biomarkers to Predict Diabetic Retinopathy in Patients with Diabetic Kidney Disease. Vision (Basel) 2023; 7:vision7020034. [PMID: 37092467 PMCID: PMC10123608 DOI: 10.3390/vision7020034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 02/05/2023] [Accepted: 03/30/2023] [Indexed: 04/25/2023] Open
Abstract
The purpose of this review is to outline the currently available circulating biomarkers to predict diabetic retinopathy (DR) in patients with diabetic kidney disease (DKD). Studies have extensively reported the association between DR and DKD, suggesting the presence of common pathways of microangiopathy. The presence of other ocular complications including diabetic cataracts may hinder the detection of retinopathy, which may affect the visual outcome after surgery. Unlike DKD screening, the detection of DR requires complex, costly machines and trained technicians. Recognizing potential biological markers related to glycation and oxidative stress, inflammation and endothelial dysfunction, basement membrane thickening, angiogenesis, and thrombosis as well as novel molecular markers involved in the microangiopathy process may be useful as predictors of retinopathy and identify those at risk of DR progression, especially in cases where retinal visualization becomes a clinical challenge. Further investigations could assist in deciding which biomarkers possess the highest predictive power to predict retinopathy in clinical settings.
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Affiliation(s)
- Laurencia Violetta
- Nephrology Division, Department of Internal Medicine, Gatot Soebroto Indonesia Army Central Hospital, Jakarta 10410, Indonesia
| | | | - Rudi Supriyadi
- Faculty of Medicine, Universitas Padjajaran, Bandung 40132, Indonesia
| | - Coriejati Rita
- Faculty of Medicine, Universitas Padjajaran, Bandung 40132, Indonesia
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Soltani S, Beigrezaei S, Malekahmadi M, Clark CCT, Abdollahi S. Circulating levels of adropin and diabetes: a systematic review and meta-analysis of observational studies. BMC Endocr Disord 2023; 23:73. [PMID: 37029398 PMCID: PMC10080945 DOI: 10.1186/s12902-023-01327-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 03/21/2023] [Indexed: 04/09/2023] Open
Abstract
OBJECTIVE Adropin, a newly identified regulatory protein has garnered attention given its potential role in metabolism regulation, especially glucose metabolism and insulin resistance. However, studies on the association between adropin and type 2 diabetes mellitus (T2DM) are equivocal. The aim of this study is to assess the association between serum adropin levels and T2DM using a systematic review and meta-analysis of observational studies. METHODS PubMed, Scopus, ISI Web of science, and Google Scholar were searched, up to August 2022, for studies that reported the association between serum levels of adropin in adults with T2DM compared to a control group without diabetes. A random-effect model was used to compute the pooled weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS Meta-analysis of 15 studies (n = 2813 participants) revealed that the serum adropin concentrations were significantly lower in patients with T2DM compared with the control group (WMD= -0.60 ng/mL, 95% CI: -0.70 to -0.49; I2 = 99.5%). Subgroup analysis also found lower concentration of adropin in patients with T2DM who were otherwise healthy compared to a control group (n = 9; WMD=-0.04 ng/ml, 95% CI= -0.06 to -0.01, p = 0.002; I2 = 96.4). CONCLUSIONS Our study showed adropin levels are lower in patients with diabetes compared to a control group without diabetes. However, the limitations of observational studies challenge the validity of the results, and further investigations are needed to confirm the veracity of these findings and additionally explore possible mechanisms.
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Affiliation(s)
- Sepideh Soltani
- Yazd Cardiovascular Research Center, Non-communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Sara Beigrezaei
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mahsa Malekahmadi
- Research Center for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Cain C T Clark
- Centre for Intelligent Healthcare, Coventry University, Coventry, CV1 5FB, UK
| | - Shima Abdollahi
- Department of Nutrition, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran.
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11
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Chen RB, Wang QY, Wang YY, Wang YD, Liu JH, Liao ZZ, Xiao XH. Feeding-induced hepatokines and crosstalk with multi-organ: A novel therapeutic target for Type 2 diabetes. Front Endocrinol (Lausanne) 2023; 14:1094458. [PMID: 36936164 PMCID: PMC10020511 DOI: 10.3389/fendo.2023.1094458] [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: 11/10/2022] [Accepted: 02/15/2023] [Indexed: 03/06/2023] Open
Abstract
Hyperglycemia, which can be caused by either an insulin deficit and/or insulin resistance, is the main symptom of Type 2 diabetes, a significant endocrine metabolic illness. Conventional medications, including insulin and oral antidiabetic medicines, can alleviate the signs of diabetes but cannot restore insulin release in a physiologically normal amount. The liver detects and reacts to shifts in the nutritional condition that occur under a wide variety of metabolic situations, making it an essential organ for maintaining energy homeostasis. It also performs a crucial function in glucolipid metabolism through the secretion of hepatokines. Emerging research shows that feeding induces hepatokines release, which regulates glucose and lipid metabolism. Notably, these feeding-induced hepatokines act on multiple organs to regulate glucolipotoxicity and thus influence the development of T2DM. In this review, we focus on describing how feeding-induced cross-talk between hepatokines, including Adropin, Manf, Leap2 and Pcsk9, and metabolic organs (e.g.brain, heart, pancreas, and adipose tissue) affects metabolic disorders, thus revealing a novel approach for both controlling and managing of Type 2 diabetes as a promising medication.
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Affiliation(s)
- Rong-Bin Chen
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
- Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Qi-Yu Wang
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
- Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Yuan-Yuan Wang
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Ya-Di Wang
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Jiang-Hua Liu
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Zhe-Zhen Liao
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Xin-Hua Xiao
- Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
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12
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Che S, Wu S, Yu P. Downregulated HDAC3 or up-regulated microRNA-296-5p alleviates diabetic retinopathy in a mouse model. Regen Ther 2022; 21:1-8. [PMID: 35619945 PMCID: PMC9121075 DOI: 10.1016/j.reth.2022.04.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 04/02/2022] [Accepted: 04/14/2022] [Indexed: 11/28/2022] Open
Abstract
Objective It has been demonstrated the efficacy of histone deacetylase 3 (HDAC3) in diabetes. Nevertheless, the function of HDAC3 in diabetic retinopathy (DR) remained largely obscure. Here, we investigated the HDAC3 effects in DR mice through the microRNA (miR)-296-5p/G protein subunit alpha i2 (GNAI2) axis. Methods The mice diabetes model was established. HDAC3, GNAI2 and miR-296-5p levels in retina tissues of DR mice were evaluated. The weight, blood glucose, Evans blue leakage in DR mice, apoptosis of retinal ganglion cells, vascular endothelial growth factor (VEGF) and malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity in DR mice were detected after miR-296-5p elevation or HDAC3 depletion. The relations among HDAC3, miR-296-5p and GNAI2 were validated. Results HDAC3 and GNAI2 expressed at a high level while miR-296-5p expressed at a low level in retina tissues of DR mice. Restoring miR-296-5p or depleting HDAC3 reduced Evans blue leakage in DR mice, attenuated apoptosis of retinal ganglion cells, reduced VEGF and MDA, and enhanced SOD activity in serum and retinal tissues of DR mice. HDAC3 repressed miR-296-5p expression by binding to its promoter region, thereby enhancing GNAI2 expression. Conclusion Depleting HDAC3 or restoring miR-296-5p suppresses apoptosis of retinal ganglion cells of DR mice via down-regulating GNAI2.
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Affiliation(s)
- Songtian Che
- Department of Ocular Fundus Disease, the Second Hospital of Jilin University, No. 4026, Yatai Street, Changchun 130041, Jilin, People's Republic of China
| | - Shuai Wu
- Department Orbital Diseases & Ocular Plastic Surgery, the Second Hospital of Jilin University, No. 4026, Yatai Street, Changchun 130041, Jilin, People's Republic of China
| | - Peng Yu
- Department of Ocular Fundus Disease, the Second Hospital of Jilin University, No. 4026, Yatai Street, Changchun 130041, Jilin, People's Republic of China
- Corresponding author. Peng Yu Department of Ocular Fundus Disease, the Second Hospital of Jilin University, No. 4026, Yatai Street, Changchun 130041, Jilin, People's Republic of China. Tel: +0431-81136535
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13
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Zhang H, Chen N. Adropin as an indicator of T2DM and its complications. FOOD SCIENCE AND HUMAN WELLNESS 2022. [DOI: 10.1016/j.fshw.2022.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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14
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Yu M, Wang D, Zhong D, Xie W, Luo J. Adropin Carried by Reactive Oxygen Species-Responsive Nanocapsules Ameliorates Renal Lipid Toxicity in Diabetic Mice. ACS APPLIED MATERIALS & INTERFACES 2022; 14:37330-37344. [PMID: 35951354 DOI: 10.1021/acsami.2c06957] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Diabetic kidney disease (DKD) is a common diabetes complication mainly caused by lipid toxicity characterized by oxidative stress. Studies have shown that adropin (Ad) regulates energy metabolism and may be an effective target to improve DKD. This study investigated the effect of exogenous Ad encapsulated in reactive oxygen species (ROS)-responsive nanocapsules (Ad@Gel) on DKD. HK2 cells were induced with high glucose (HG) and intervened with Ad@Gel. A diabetes mouse model was established using HG and high-fat diet combined with streptozotocin and treated with Ad@Gel to observe its effects on renal function, pathological damage, lipid metabolism, and oxidative stress. Results showed that Ad@Gel could protect HK2 from HG stimulation in vitro. It also effectively controls blood glucose and lipid levels, improves renal function, inhibits excessive production of ROS, protects mitochondria from damage, improves lipid deposition in renal tissues, and downregulates the expression of lipogenic proteins SEBP-1 and ADRP in DKD mice. In HG-induced HK2 cells or the kidney of DKD patients, the low expression of neuronatin (Nnat) and high expression of translocator protein (TSPO) were observed. Knockdown Nnat or overexpression of TSPO significantly reversed the effect of Ad@Gel on improving mitochondrial damage. In addition, knockdown Nnat also significantly reversed the effect of Ad@Gel on lipid metabolism. The results suggest that the effect of Ad on DKD may be achieved by activating Nnat to improve lipid metabolism and inhibit TSPO activity, thereby enhancing mitochondrial function.
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Affiliation(s)
- Mingchuan Yu
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang 330006, Jiangxi, P. R. China
| | - Di Wang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang 330006, Jiangxi, P. R. China
| | - Da Zhong
- Nanchang University, Nanchang 330006, Jiangxi, P. R. China
| | - Weichang Xie
- Nanchang University, Nanchang 330006, Jiangxi, P. R. China
| | - Jun Luo
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang 330006, Jiangxi, P. R. China
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15
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Adropin’s Role in Energy Homeostasis and Metabolic Disorders. Int J Mol Sci 2022; 23:ijms23158318. [PMID: 35955453 PMCID: PMC9369016 DOI: 10.3390/ijms23158318] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 01/27/2023] Open
Abstract
Adropin is a novel 76-amino acid-peptide that is expressed in different tissues and cells including the liver, pancreas, heart and vascular tissues, kidney, milk, serum, plasma and many parts of the brain. Adropin, encoded by the Enho gene, plays a crucial role in energy homeostasis. The literature review indicates that adropin alleviates the degree of insulin resistance by reducing endogenous hepatic glucose production. Adropin improves glucose metabolism by enhancing glucose utilization in mice, including the sensitization of insulin signaling pathways such as Akt phosphorylation and the activation of the glucose transporter 4 receptor. Several studies have also demonstrated that adropin improves cardiac function, cardiac efficiency and coronary blood flow in mice. Adropin can also reduce the levels of serum triglycerides, total cholesterol and low-density lipoprotein cholesterol. In contrast, it increases the level of high-density lipoprotein cholesterol, often referred to as the beneficial cholesterol. Adropin inhibits inflammation by reducing the tissue level of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6. The protective effect of adropin on the vascular endothelium is through an increase in the expression of endothelial nitric oxide synthase. This article provides an overview of the existing literature about the role of adropin in different pathological conditions.
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16
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Midena E, Frizziero L, Midena G, Pilotto E. Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2021; 259:3549-3560. [PMID: 34216255 PMCID: PMC8589786 DOI: 10.1007/s00417-021-05285-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 06/05/2021] [Accepted: 06/11/2021] [Indexed: 02/07/2023] Open
Abstract
Purpose This article aims to review the impact of detecting and quantifying intraocular biomarkers (liquid biopsy) in both aqueous and vitreous humor in eyes of people affected by diabetes mellitus. Methods This is a detailed review about aqueous and/or vitreous humor sampling in human diabetic eyes for proteomic and/or metabolomic analysis contributing to the understanding of the pathophysiology and treatment effects of diabetic retinopathy. Results Aqueous and vitreous humor molecular biomarkers proved to be directly correlated to each other and valuable to study retinal conditions. Moreover, proteomic and metabolomic analysis showed that the biomarkers of neuroinflammation, neurodegeneration, and vasculopathy are detectable in intraocular fluids and that their concentration changes in different stages of disease, and in response to treatment of all diabetic retinopathy aspects, mainly diabetic macular edema and proliferative retinopathy. Conclusions Liquid biopsy offers the possibility to improve our knowledge of intraocular eye disease induced by diabetes mellitus. The exact quantification of intraocular biomarkers contributes to the precision medicine approach even in the diabetic retinopathy scenario. The diffusion of this approach should be encouraged to have quantifiable information directly from the human model, which may be coupled with imaging data.
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Affiliation(s)
- Edoardo Midena
- Department of Neuroscience-Ophthalmology, University of Padova, Padova, Italy. .,IRCCS-Fondazione Bietti, Rome, Italy.
| | - Luisa Frizziero
- Department of Neuroscience-Ophthalmology, University of Padova, Padova, Italy
| | | | - Elisabetta Pilotto
- Department of Neuroscience-Ophthalmology, University of Padova, Padova, Italy
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17
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Ziarniak K, Dudek M, Matuszewska J, Bijoch Ł, Skrzypski M, Celichowski J, Sliwowska JH. Two weeks of moderate intensity locomotor training increased corticosterone concentrations but did not alter the number of adropin-immunoreactive cells in the hippocampus of diabetic type 2 and control rats. Acta Histochem 2021; 123:151751. [PMID: 34229193 DOI: 10.1016/j.acthis.2021.151751] [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: 02/24/2021] [Revised: 06/18/2021] [Accepted: 06/29/2021] [Indexed: 10/20/2022]
Abstract
Adropin (ADR) plays a role in metabolism regulation and its alterations in obesity and diabetes have been found. Treatment with ADR was beneficial in metabolic diseases, and physical exercise increased ADR concentrations in obese patients. However, data on the distribution of ADR in the brain are sparse. The role of metabolic status and physical exercise on its expression in the brain is undiscovered. We hypothesized that diabetes type 2 (DM2) and/or exercise will alter number of ADR-immunoractive (-ir) cells in the rat brain. Animals were divided into groups: diabetes type 2 (receiving high-fat diet and injections of streptozotocin) and control (fed laboratory chow diet; C). Rats were further divided into: running group (2 weeks of forced exercise on a treadmill) and non-running group. Body mass, metabolic and hormonal profiles were assessed. Immunohistochemistry was run to study ADR-ir cells in the brain. We found that: 1) in DM2 animals, running decreased insulin and increased glucose concentrations; 2) in C rats, running decreased insulin concentrations and had no effect on glucose concentration in blood; 3) running increased corticosterone (CORT) concentrations in DM2 and C rats; 4) ADR-ir cells were detected in the hippocampus and ADR-ir fibers in the arcuate nucleus of the hypothalamus, which is a novel location; 5) metabolic status and running, however, did not change number of these cells. We concluded that 2 weeks of forced moderate intensity locomotor training induced stress response present as increased concentration of CORT and did not influence number of ADR-ir cells in the brain.
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18
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Kolben Y, Weksler-Zangen S, Ilan Y. Adropin as a potential mediator of the metabolic system-autonomic nervous system-chronobiology axis: Implementing a personalized signature-based platform for chronotherapy. Obes Rev 2021; 22:e13108. [PMID: 32720402 DOI: 10.1111/obr.13108] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/15/2020] [Accepted: 05/15/2020] [Indexed: 02/07/2023]
Abstract
Adropin is a peptide hormone, which plays a role in energy homeostasis and controls glucose and fatty acid metabolism. Its levels correlate with changes in carbohydrate-lipid metabolism, metabolic diseases, central nervous system function, endothelial function and cardiovascular disease. Both metabolic pathways and adropin are regulated by the circadian clocks. Here, we review the roles of the autonomic nervous system and circadian rhythms in regulating metabolic pathways and energy homeostasis. The beneficial effects of chronotherapy in various systems are discussed. We suggest a potential role for adropin as a mediator of the metabolic system-autonomic nervous system axis. We discuss the possibility of establishing an individualized adropin and circadian rhythm-based platform for implementing chronotherapy, and variability signatures for improving the efficacy of adropin-based therapies are discussed.
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Affiliation(s)
- Yotam Kolben
- Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel
| | - Sarah Weksler-Zangen
- Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel
| | - Yaron Ilan
- Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel
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19
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Mogulkoc R, Dasdelen D, Baltaci SB, Baltaci AK, Sivrikaya A. The effect of thyroid dysfunction and treatment on adropin, asprosin and preptin levels in rats. Horm Mol Biol Clin Investig 2020; 42:37-42. [PMID: 33781005 DOI: 10.1515/hmbci-2020-0058] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 11/14/2020] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Thyroid hormones have important roles in normal development and energy regulating mechanisms as well as signaling mechanisms that affect energy consumption through central and peripheral pathways. The aim of this study was to determine the effects of thyroid dysfunction on adropin, asprosin and preptin levels in rat. METHODS The study was performed on the 38 male Wistar-albino rats. Experiment groups were designed as follows. 1-Control, 2-Hypothyroidism; To induce hypothyroidism PTU was applied by intraperitoneal as 10 mg/kg/day for 2 weeks. 3-Hypothyroidism + Thyroxine; Previously animals were made with hypothyroidism by 1 week PTU application and then 1 week l-thyroxine was given by intraperitoneal as 1.5 mg/kg/day. 4-Hyperthyroidism; Rats were made with hyperthyroidism by 3 weeks l-thyroxine (0.3 mg/kg/day). 5-Hyperthyroidism + PTU; Animals were made hyperthyroisim by l-thyroxine as groups 4, then 1 week PTU was applied to treatment of hiperthyrodism. At the end of supplementation animals were sacrificed and blood samples were collected for FT3, FT4, adropin, asprosin, preptin analysis. RESULTS FT3 ve FT4 levels were reduced significantly in hypothyroidism while increased in hyperthyroidism (p<0.001). Hipothyrodism led to reduces adropin, asprosin and preptin levels. And also hyperthyroidism reduced adropin and preptin levels (p<0.001). CONCLUSIONS The results of study show that experimental hypothyroidism and hyperthyroidism lead to significantly change to adropin, asprosin and preptin levels. However, correction of thyroid function caused to normals levels in asprosin and preptin.
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Affiliation(s)
- Rasim Mogulkoc
- Medical School, Deparment of Physiology, Selcuk University, Konya, Turkey
| | - Dervis Dasdelen
- Medical School, Deparment of Physiology, Selcuk University, Konya, Turkey
| | | | | | - Abdullah Sivrikaya
- Medical School, Deparment of Biochemistry, Selcuk University, Konya, Turkey
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20
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Li B, Li N, Guo S, Zhang M, Li J, Zhai N, Wang H, Zhang Y. The changing features of serum adropin, copeptin, neprilysin and chitotriosidase which are associated with vascular endothelial function in type 2 diabetic retinopathy patients. J Diabetes Complications 2020; 34:107686. [PMID: 32768333 DOI: 10.1016/j.jdiacomp.2020.107686] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 07/14/2020] [Accepted: 07/19/2020] [Indexed: 12/21/2022]
Abstract
AIMS Adropin (AD), copeptin (CP), neprilysin (NEP) and chitotriosidase (CHIT1) have been associated with the regulation of vascular endothelial function. In this work, we analyzed the plasma concentrations of cytokines (AD, CP, NEP and CHIT1) in type 2 diabetic patients with or without retinopathy (DR) to predict the risk of DR for diabetic patients. METHOD A total of 392 patients diagnosed as type 2 diabetes mellitus (T2DM) and 120 healthy volunteers as a control group were enrolled in this study. T2DM patients were divided into three groups: diabetes without retinopathy (NDR, n = 174) group, non-proliferative diabetic retinopathy (NPDR, n = 118) group and proliferative diabetic retinopathy (PDR, n = 100) group. The serum AD, CP, NEP and CHIT1 levels of subjects were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS We reported a significant decrease in AD and a significant increase in CP, NEP and CHIT1 in NDR as well as DR patients when compared with controls (p < 0.05), the lower level of AD and significantly higher levels of CP, NEP and CHIT1 were seen in DR patients compared to NDR group (p < 0.05), at the same time, we observed the lowest level of AD and the highest levels of CP, NEP and CHIT1 in the PDR group. Logistic regression analysis showed that AD was a protective factor for DR, conversely, CP, NEP and CHIT1 were the independent risk factors (p < 0.05). Moreover, receiver operating characteristic curve analyses indicated that CP had greater diagnosis capacity with an AUC (the areas under the ROC curve) of 0.901 than AD, NEP, CHIT1 for DR patients. CONCLUSION The decreased AD level and the elevated CP, NEP and CHIT1 levels involved in vascular endothelial function may be evidence facilitating the presence of DR. Thereby they can be explored to use as promising non-invasive biomarkers for prediction of DR severity, distinguishing DR from diabetic patients.
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Affiliation(s)
- Baoxin Li
- Department of Endocrinology, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China; Hebei Provincial Center for Optical Sensing Innovations, Baoding 071000, Hebei, China
| | - Na Li
- Department of Endocrinology, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China; Hebei Provincial Center for Optical Sensing Innovations, Baoding 071000, Hebei, China
| | - Shuqin Guo
- Department of Endocrinology, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China; Hebei Provincial Center for Optical Sensing Innovations, Baoding 071000, Hebei, China
| | - Mali Zhang
- Department of Endocrinology, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China; Hebei Provincial Center for Optical Sensing Innovations, Baoding 071000, Hebei, China
| | - Jie Li
- Department of Endocrinology, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China; Hebei Provincial Center for Optical Sensing Innovations, Baoding 071000, Hebei, China
| | - Na Zhai
- Department of Endocrinology, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China; Hebei Provincial Center for Optical Sensing Innovations, Baoding 071000, Hebei, China
| | - He Wang
- Department of Endocrinology, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China; Hebei Provincial Center for Optical Sensing Innovations, Baoding 071000, Hebei, China
| | - Yunliang Zhang
- Department of Endocrinology, Baoding NO.1 Central Hospital, Baoding 071000, Hebei, China; Hebei Provincial Center for Optical Sensing Innovations, Baoding 071000, Hebei, China.
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21
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Pentraxin-3 and adropin as inflammatory markers of early renal damage in type 2 diabetes patients. Int Urol Nephrol 2020; 52:2145-2152. [DOI: 10.1007/s11255-020-02568-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 07/07/2020] [Indexed: 12/11/2022]
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