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Bashandy SAE, Elbaset MA, Ibrahim FAA, Abdelrahman SS, Moussa SAA, El-Seidy AMA. Management of cardiovascular disease by cerium oxide nanoparticles via alleviating oxidative stress and adipokine abnormalities. Sci Rep 2025; 15:5709. [PMID: 39962072 PMCID: PMC11833101 DOI: 10.1038/s41598-025-85794-6] [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: 01/25/2024] [Accepted: 01/06/2025] [Indexed: 02/20/2025] Open
Abstract
The current study aimed to evaluate the role of cerium oxide nanoparticles (C-1), a potent antioxidant, in the medication of cardiovascular disease in obese animal model. C-1 was prepared using a modified sonication sol-gel method. Thirty-two adult male rats were equally divided into 4 groups (n=8/each). The first (control) and second (obese) groups are not treated while the obese rats in the third and fourth groups were given 15 and 30 mg/kg C-1(IP), respectively, for 8 weeks. Parameters of insulin resistance, adipocyte hormones, inflammatory markers, lipid profile, cardiac enzymes and cardiac iron content (C-Fe) were estimated. Moreover, histological study and immunohistochemical stain for inducible nitric oxide synthase (INOS) for cardiac and aortic tissues were performed. The XRD patterns of C-1 showed narrow symmetric diffraction peaks. The particle diameters were calculated from the TEM histogram (21.09 nm) and the Debye-Scherrer Method (20.74 nm) which were very similar. Using the most intense peak ( 28 . 47 ∘ ), structural parameters were calculated including nano-crystallite size, Micro-strain, Lorentz factor, Thomson polarization parameter, and Lorentz polarization parameter. BET was used to calculate The total surface area (ST ), and specific surface area (SBET ). The XPS survey spectrum of C-1 showed peaks for C-1s, O-1s and Ce-3d. The treatment of obese rats with C-1 led to a significant decrease in body weight, C-Fe , plasma leptin, tumor necrosis factor-alpha (TNF α ), interleukin-6 (IL6), C-reactive protein (CRP), resistin, cholesterol, triglycerides, low-density lipoprotein (LDL), Troponin, Creatinine Kinase-MB (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA) in cardiac tissue or in plasma. Also, C-1 lowered plasma monocyte chemoattractant protein-1 (MCP-1), Epithelial Neutrophil-Activating Peptide (ENA-78), and insulin and glucose levels in obese rats. Furthermore, C-1 alleviated the increase of cardiac iNOS. Moreover, C-1 mitigated pathological changes of cardiac muscle and aorta observed in obese rats. On the other hand, C-1 enhanced adiponectin, cardiac glutathione (GSH) and superoxide dismutase (SOD) in obese rats. The effect of C-1 is dose-dependent ( 30 mg/kg of C-1 is more evident than 15 mg/kg). The modified synthesis method may lead to a smaller particle size than that reported in our previously reported work. The XRD patterns of C-1 indicate its cubic structure with space group F m -3 m (225) which was matched by code id 4343161 from COD. The Raman spectrum of C-1 indicates the absence of rearrangement oxygen atoms, the presence of oxygen in its fluorite lattice positions, and the oxygen vacancies in C-1 and the Ce vibration model (F2g). The presence of ten peaks in the high-resolution Ce-3d XP spectrum indicates the existence of both Ce3+ and Ce4+. C-1 showed therapeutic efficacy in atherosclerosis and cardiac muscle abnormalities associated with obese rats, probably because of their antioxidant and anti-inflammatory properties, which lead to lowering oxidative stress.
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Affiliation(s)
- Samir A E Bashandy
- Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, El-bohouth St., P.O. 12622, Dokki, Cairo, Egypt
| | - Marawan A Elbaset
- Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, El-bohouth St., P.O. 12622, Dokki, Cairo, Egypt.
| | - Fatma A A Ibrahim
- Department of Biochemistry, Biotechnology Research Institute, National Research Centre, El-bohouth St., P.O. 12622, Dokki, Cairo, Egypt
| | - Sahar S Abdelrahman
- Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Sherif A Abdelmottaleb Moussa
- Department of Biochemistry, Biotechnology Research Institute, National Research Centre, El-bohouth St., P.O. 12622, Dokki, Cairo, Egypt
| | - Ahmed M A El-Seidy
- Inorganic Chemistry Department, Advanced Materials Technology & Mineral Resources Research Institute, National Research Centre, El-bohouth St., P.O. 12622, Dokki, Cairo, Egypt.
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Yaqoob MU, Qi Y, Hou J, Zhe L, Zhu X, Wu P, Li Z, Wang M, Li Y, Yue M. Coated cysteamine and choline chloride could be potential feed additives to mitigate the harmful effects of fatty liver hemorrhagic syndrome in laying hens caused by high-energy low-protein diet. Poult Sci 2024; 103:104296. [PMID: 39305615 PMCID: PMC11437759 DOI: 10.1016/j.psj.2024.104296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/30/2024] [Accepted: 08/31/2024] [Indexed: 10/01/2024] Open
Abstract
The research aimed to examine the impact of coated cysteamine (CS) and choline chloride (CC) on relieving the pathological effects of fatty liver hemorrhagic syndrome (FLHS) in laying hens. FLHS was induced by a high-energy low-protein (HELP) diet. Ninety laying hens were equally divided into 5 treatments with 6 replicates per treatment (3 hens/replicate). The control treatment (Cont) was fed a basal diet, while the remaining treatments were fed a HELP diet. Under the HELP dietary plan, 4 treatments were set by a 2 × 2 factorial design. Two levels of CS (CS-: 0.00 mg/kg CS; CS+: 100 mg/kg diet) and 2 levels of choline (CC-: 1,182 mg/kg; CC+: 4,124 mg/kg) were set and named CS-CC- (HELP), CS+CC-, CS-CC+ and CS+CC+. The liver of the CS-CC- (HELP) group became yellowish-brown and greasy, with hemorrhages and bleeding spots. Elevated (P < 0.05) plasma and hepatic ALT and AST and hepatic MDA levels, combined with reduced (P < 0.05) plasma and hepatic SOD and GSH-Px activities in the CS-CC- (HELP) group proved that FLHS was successfully induced. Dietary supplementation of CS, CC, or both (CS+CC+) in HELP diets relieved the pathological changes, significantly (P < 0.05) reduced the AST and ALT levels, and strengthened the antioxidant potential in laying hens under FLHS. The highest (P < 0.001) plasma adiponectin concentration was observed in the CS+CC- and lowest in the CS-CC- (HELP) group. In addition, CS and CC supplementation lowers the elevated levels of hepatic T-CHO and TG by increasing the HDL-C and reducing LDL-C levels (P < 0.05) than CS-CC- (HELP) group. CS supplementation, either alone or with CC, helps laying hens restore their egg production. It could be stated that CS and CC supplements could ameliorate the adverse effects of FLHS by regulating antioxidant enzymes activities, modulating the hepatic lipid metabolism, and restoring the production performance in laying hens. Hence, adding CS and CC could be an effective way to reduce FLHS in laying hens.
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Affiliation(s)
- Muhammad Umar Yaqoob
- College of Animal Science, Zhejiang University, Hangzhou 310058, China; Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Yingying Qi
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Jia Hou
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Li Zhe
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Xiangde Zhu
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Peng Wu
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Zhefeng Li
- Provincial Key Agricultural Enterprise Research Institute of King Techina, Hangzhou King Techina Feed Co., Ltd. Zhejiang Hangzhou 311107, China
| | - Minqi Wang
- College of Animal Science, Zhejiang University, Hangzhou 310058, China
| | - Yan Li
- College of Animal Science, Zhejiang University, Hangzhou 310058, China
| | - Min Yue
- College of Animal Science, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
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Shi H, Sim YJ. Effects of weekend-focused exercise on obesity-related hormones and metabolic syndrome markers in male high school students. J Exerc Rehabil 2024; 20:227-234. [PMID: 39781501 PMCID: PMC11704708 DOI: 10.12965/jer.2448632.316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 11/21/2024] [Accepted: 11/24/2024] [Indexed: 01/12/2025] Open
Abstract
To examine the changes in obesity-related hormones and metabolic syndrome markers in male high school students with obesity following a weekend-focused moderate- or high-intensity exercise program at the recommended weekly physical activity level, or a program of regular exercise 3 times a week at moderate intensity, over a 10-week period. Forty-eight male high school students who were obese with a body fat percentage of ≥25% were randomly assigned to one of three groups: a regular moderate-intensity exercise group (n=17) that freely selected and performed moderate-intensity aerobic and resistance training exercises, every Monday, Wednesday, and Friday, for a total of 150-300 min/wk; a weekend-focused moderate-intensity exercise group (n=15) that freely selected and performed aerobic and resistance training exercises every Saturday for 150-300 min; and a week-end-focused high-intensity exercise group (n=16) that freely selected and performed aerobic and resistance training exercises every Sunday for 75-150 min. Insulin and leptin levels significantly decreased in all the groups, with the greatest reduction in the regular exercise group. Abdominal circumference and triglyceride levels significantly decreased in all the groups. Fasting glucose decreased only in the regular exercise group. High-density lipoprotein cholesterol significantly increased in both the regular and weekend-focused moderate-intensity exercise groups. No significant differences in adiponectin levels, and systolic and diastolic blood pressure were observed between the groups. A weekend-focused exercise program has health effects similar to those of regular exercise, highlighting the importance of meeting the recommended weekly physical activity levels.
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Affiliation(s)
- Haoyu Shi
- Department of Physical Education, Kunsan National University, Gunsan,
Korea
| | - Young-Je Sim
- Department of Physical Education, Kunsan National University, Gunsan,
Korea
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Zhao YQ, Ren YF, Li BB, Wei C, Yu B. The mysterious association between adiponectin and endometriosis. Front Pharmacol 2024; 15:1396616. [PMID: 38813109 PMCID: PMC11133721 DOI: 10.3389/fphar.2024.1396616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 04/29/2024] [Indexed: 05/31/2024] Open
Abstract
Adiponectin is a pleiotropic cytokine predominantly derived from adipose tissue. In addition to its role in regulating energy metabolism, adiponectin may also be related to estrogen-dependent diseases, and many studies have confirmed its involvement in mediating diverse biological processes, including apoptosis, autophagy, inflammation, angiogenesis, and fibrosis, all of which are related to the pathogenesis of endometriosis. Although many researchers have reported low levels of adiponectin in patients with endometriosis and suggested that it may serve as a protective factor against the development of the disease. Therefore, the purpose of this review was to provide an up-to-date summary of the roles of adiponectin and its downstream cytokines and signaling pathways in the aforementioned biological processes. Further systematic studies on the molecular and cellular mechanisms of action of adiponectin may provide novel insights into the pathophysiology of endometriosis as well as potential therapeutic targets.
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Affiliation(s)
| | | | - Bing-Bing Li
- College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, Shandong Province, China
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Han Y, Sun Q, Chen W, Gao Y, Ye J, Chen Y, Wang T, Gao L, Liu Y, Yang Y. New advances of adiponectin in regulating obesity and related metabolic syndromes. J Pharm Anal 2024; 14:100913. [PMID: 38799237 PMCID: PMC11127227 DOI: 10.1016/j.jpha.2023.12.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 11/18/2023] [Accepted: 12/07/2023] [Indexed: 05/29/2024] Open
Abstract
Obesity and related metabolic syndromes have been recognized as important disease risks, in which the role of adipokines cannot be ignored. Adiponectin (ADP) is one of the key adipokines with various beneficial effects, including improving glucose and lipid metabolism, enhancing insulin sensitivity, reducing oxidative stress and inflammation, promoting ceramides degradation, and stimulating adipose tissue vascularity. Based on those, it can serve as a positive regulator in many metabolic syndromes, such as type 2 diabetes (T2D), cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), sarcopenia, neurodegenerative diseases, and certain cancers. Therefore, a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors. The modulation of ADP genes, multimerization, and secretion covers the main processes of ADP generation, providing a comprehensive orientation for the development of more appropriate therapeutic strategies. In order to have a deeper understanding of ADP, this paper will provide an all-encompassing review of ADP.
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Affiliation(s)
- Yanqi Han
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Qianwen Sun
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Wei Chen
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Yue Gao
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Jun Ye
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Yanmin Chen
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Tingting Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Lili Gao
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Yuling Liu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Yanfang Yang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
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Alruhaimi RS, Mostafa-Hedeab G, Abduh MS, Bin-Ammar A, Hassanein EHM, Kamel EM, Mahmoud AM. A flavonoid-rich fraction of Euphorbia peplus attenuates hyperglycemia, insulin resistance, and oxidative stress in a type 2 diabetes rat model. Front Pharmacol 2023; 14:1204641. [PMID: 37397470 PMCID: PMC10311489 DOI: 10.3389/fphar.2023.1204641] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 06/01/2023] [Indexed: 07/04/2023] Open
Abstract
Background: Type 2 diabetes (T2D) is a metabolic disorder characterized by insulin resistance (IR) and hyperglycemia. Plants are valuable sources of therapeutic agents for the management of T2D. Euphorbia peplus has been widely used as a traditional medicine for the treatment of various diseases, but its beneficial role in T2D has not been fully explored. Methods: The anti-diabetic efficacy of E. peplus extract (EPE) was studied using rats with T2D induced by high-fat diet (HFD) and streptozotocin (STZ). The diabetic rats received 100, 200, and 400 mg/kg EPE for 4 weeks. Results: Phytochemical fractionation of the aerial parts of E. peplus led to the isolation of seven known flavonoids. Rats with T2D exhibited IR, impaired glucose tolerance, decreased liver hexokinase and glycogen, and upregulated glycogen phosphorylase, glucose-6-phosphatase (G-6-Pase), and fructose-1,6-bisphosphatase (F-1,6-BPase). Treatment with 100, 200, and 400 mg/kg EPE for 4 weeks ameliorated hyperglycemia, IR, liver glycogen, and the activities of carbohydrate-metabolizing enzymes. EPE attenuated dyslipidemia, serum transaminases, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and liver lipid accumulation, nuclear factor (NF)-κB p65, and lipid peroxidation, nitric oxide and enhanced antioxidants. All EPE doses upregulated serum adiponectin and liver peroxisome proliferator-activated receptor γ (PPARγ) in HFD/STZ-induced rats. The isolated flavonoids showed in silico binding affinity toward hexokinase, NF-κB, and PPARγ. Conclusion: E. peplus is rich in flavonoids, and its extract ameliorated IR, hyperglycemia, dyslipidemia, inflammation and redox imbalance, and upregulated adiponectin and PPARγ in rats with T2D.
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Affiliation(s)
- Reem S. Alruhaimi
- Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Gomaa Mostafa-Hedeab
- Pharmacology Department, Medical College, Jouf University, Sakaka, Saudi Arabia
- Pharmacology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Maisa Siddiq Abduh
- Immune Responses in Different Diseases Research Group, Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Albandari Bin-Ammar
- Department of Clinical Nutrition, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia
| | - Emad H. M. Hassanein
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
| | - Emadeldin M. Kamel
- Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
| | - Ayman M. Mahmoud
- Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, United Kingdom
- Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
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Hosseini SV, Hosseini SA, Khazraei H, Lankarani KB. Adiponectin and leptin levels of patients after sleeve gastrectomy, Roux-en-Y gastric bypass, and single anastomosis sleeve ileal bypass surgeries. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2023; 28:42. [PMID: 37405072 PMCID: PMC10315400 DOI: 10.4103/jrms.jrms_77_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/11/2023] [Accepted: 04/03/2023] [Indexed: 07/06/2023]
Abstract
Background Bariatric surgery is an appropriate treatment for obese patients with metabolic syndrome. Adipose tissue is an active endocrine tissue secreting leptin and adiponectin that affect body metabolism. Nowadays, a high incidence of metabolic syndrome with an increased risk of serious diseases has been detected in Shiraz. This study aimed to assess the levels of leptin and adiponectin as well as the adiponectin-to-leptin ratio in three different bariatric surgeries among obese patients in Shiraz. The results will play an important role in physicians' choice of surgery by distinguishing the effects of these three bariatric surgeries. Materials and Methods The serum adiponectin and leptin levels were measured using enzyme-linked immunosorbent assay. Blood glucose, lipid profile, weight, and liver enzyme level were measured before and 7 months after surgery. Results This clinical trial was conducted on 81 obese patients who underwent sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and single anastomosis sleeve ileal (SASI) bypass surgeries. The results revealed a decrease in fasting blood sugar and triglyceride (TG) levels 7 months after the surgeries. In addition, decrease of body mass index (BMI) was more significantly in the SASI group (12.8 ± 3 4.95) compared to the Roux-en-Y gastric group (8.56 ± 4.61) (P = 0.026). Besides, a more significant improvement in liver function was observed in SG (P < 0.05). Furthermore, the results revealed a significant difference among the three groups regarding the increase in the adiponectin level (P = 0.039). Decrease in the leptin level and increase in the adiponectin level were more significant after the RYGB surgery compared to the SG group (P < 0.05). Conclusion The three bariatric surgeries were effective in increasing the adiponectin level and decreasing the leptin levels. The surgeries also changed the metabolic risk factors including TGs, high-density lipoprotein, fasting blood glucose, and BMI.
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Affiliation(s)
| | - Seyed Ali Hosseini
- Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hajar Khazraei
- Colorectal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kamran B Lankarani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
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El-Hattab MY, Sinclair N, Liszewski JN, Schrodt MV, Herrmann J, Klingelhutz AJ, Sander EA, Ankrum JA. Native adiponectin plays a role in the adipocyte-mediated conversion of fibroblasts to myofibroblasts. J R Soc Interface 2023; 20:20230004. [PMID: 37132228 PMCID: PMC10154927 DOI: 10.1098/rsif.2023.0004] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 04/11/2023] [Indexed: 05/04/2023] Open
Abstract
Adipocytes regulate tissues through production of adipokines that can act both locally and systemically. Adipocytes also have been found to play a critical role in regulating the healing process. To better understand this role, we developed a three-dimensional human adipocyte spheroid system that has an adipokine profile similar to in vivo adipose tissues. Previously, we found that conditioned medium from these spheroids induces human dermal fibroblast conversion into highly contractile, collagen-producing myofibroblasts through a transforming growth factor beta-1 (TGF-β1) independent pathway. Here, we sought to identify how mature adipocytes signal to dermal fibroblasts through adipokines to induce myofibroblast conversion. By using molecular weight fractionation, heat inactivation and lipid depletion, we determined mature adipocytes secrete a factor that is 30-100 kDa, heat labile and lipid associated that induces myofibroblast conversion. We also show that the depletion of the adipokine adiponectin, which fits those physico-chemical parameters, eliminates the ability of adipocyte-conditioned media to induce fibroblast to myofibroblast conversion. Interestingly, native adiponectin secreted by cultured adipocytes consistently elicited a stronger level of α-smooth muscle actin expression than exogenously added adiponectin. Thus, adiponectin secreted by mature adipocytes induces fibroblast to myofibroblast conversion and may lead to a phenotype of myofibroblasts distinct from TGF-β1-induced myofibroblasts.
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Affiliation(s)
- Mariam Y. El-Hattab
- Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA
| | - Noah Sinclair
- Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA
| | - Jesse N. Liszewski
- Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA
| | - Michael V. Schrodt
- Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA
| | - Jacob Herrmann
- Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA
| | - Aloysius J. Klingelhutz
- Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
- Department of Orthopedics and Rehabilitation, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Edward A. Sander
- Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA
- Department of Orthopedics and Rehabilitation, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - James A. Ankrum
- Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA
- University of Iowa Fraternal Order of Eagles Diabetes Research Center, Iowa City 52242, IA, USA
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Kirichenko TV, Markina YV, Bogatyreva AI, Tolstik TV, Varaeva YR, Starodubova AV. The Role of Adipokines in Inflammatory Mechanisms of Obesity. Int J Mol Sci 2022; 23:ijms232314982. [PMID: 36499312 PMCID: PMC9740598 DOI: 10.3390/ijms232314982] [Citation(s) in RCA: 88] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 11/25/2022] [Accepted: 11/27/2022] [Indexed: 12/02/2022] Open
Abstract
Adipokines are currently widely studied cellular signaling proteins produced by adipose tissue and involved in various processes, including inflammation; energy and appetite modulation; lipid and glucose metabolism; insulin sensitivity; endothelial cell functioning; angiogenesis; the regulation of blood pressure; and hemostasis. The current review attempted to highlight the key functions of adipokines in the inflammatory mechanisms of obesity, its complications, and its associated diseases. An extensive search for materials on the role of adipokines in the pathogenesis of obesity was conducted online using the PubMed and Scopus databases until October 2022.
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Affiliation(s)
- Tatiana V. Kirichenko
- Petrovsky National Research Center of Surgery, 119991 Moscow, Russia
- Chazov National Medical Research Center of Cardiology, 121552 Moscow, Russia
| | - Yuliya V. Markina
- Petrovsky National Research Center of Surgery, 119991 Moscow, Russia
- Correspondence:
| | | | | | - Yurgita R. Varaeva
- Federal Research Centre for Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia
| | - Antonina V. Starodubova
- Federal Research Centre for Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia
- Medical Faculty, Pirogov Russian National Research Medical University, 117997 Moscow, Russia
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Marchi PH, Vendramini THA, Perini MP, Zafalon RVA, Amaral AR, Ochamotto VA, Da Silveira JC, Dagli MLZ, Brunetto MA. Obesity, inflammation, and cancer in dogs: Review and perspectives. Front Vet Sci 2022; 9:1004122. [PMID: 36262532 PMCID: PMC9573962 DOI: 10.3389/fvets.2022.1004122] [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: 07/26/2022] [Accepted: 08/31/2022] [Indexed: 11/13/2022] Open
Abstract
Obesity is the most common nutritional disease in dogs, and its prevalence has increased in recent decades. Several countries have demonstrated a prevalence of obesity in dogs similar to that observed in humans. Chronic low-grade inflammation is a prominent basis used to explain how obesity results in numerous negative health consequences. This is well known and understood, and recent studies have pointed to the association between obesity and predisposition to specific types of cancers and their complications. Such elucidations are important because, like obesity, the prevalence of cancer in dogs has increased in recent decades, establishing cancer as a significant cause of death for these animals. In the same way, intensive advances in technology in the field of human and veterinary medicine (which even proposes the use of animal models) have optimized existing therapeutic methods, led to the development of innovative treatments, and shortened the time to diagnosis of cancer. Despite the great challenges, this review aims to highlight the evidence obtained to date on the association between obesity, inflammation, and cancer in dogs, and the possible pathophysiological mechanisms that link obesity and carcinogenesis. The potential to control cancer in animals using existing knowledge is also presented.
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Affiliation(s)
- Pedro H. Marchi
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Thiago H. A. Vendramini
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Mariana P. Perini
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Rafael V. A. Zafalon
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Andressa R. Amaral
- Veterinary Nutrology Service, Veterinary Teaching Hospital of the School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
| | - Vanessa A. Ochamotto
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Juliano C. Da Silveira
- Laboratory of Molecular, Morphophysiology and Development (LMMD), Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, Brazil
| | - Maria L. Z. Dagli
- Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Science of the University of São Paulo, São Paulo, Brazil
| | - Marcio A. Brunetto
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil,Veterinary Nutrology Service, Veterinary Teaching Hospital of the School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil,*Correspondence: Marcio A. Brunetto
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11
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Renzini A, D’Onghia M, Coletti D, Moresi V. Histone Deacetylases as Modulators of the Crosstalk Between Skeletal Muscle and Other Organs. Front Physiol 2022; 13:706003. [PMID: 35250605 PMCID: PMC8895239 DOI: 10.3389/fphys.2022.706003] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 01/31/2022] [Indexed: 12/14/2022] Open
Abstract
Skeletal muscle plays a major role in controlling body mass and metabolism: it is the most abundant tissue of the body and a major source of humoral factors; in addition, it is primarily responsible for glucose uptake and storage, as well as for protein metabolism. Muscle acts as a metabolic hub, in a crosstalk with other organs and tissues, such as the liver, the brain, and fat tissue. Cytokines, adipokines, and myokines are pivotal mediators of such crosstalk. Many of these circulating factors modulate histone deacetylase (HDAC) expression and/or activity. HDACs form a numerous family of enzymes, divided into four classes based on their homology to their orthologs in yeast. Eleven family members are considered classic HDACs, with a highly conserved deacetylase domain, and fall into Classes I, II, and IV, while class III members are named Sirtuins and are structurally and mechanistically distinct from the members of the other classes. HDACs are key regulators of skeletal muscle metabolism, both in physiological conditions and following metabolic stress, participating in the highly dynamic adaptative responses of the muscle to external stimuli. In turn, HDAC expression and activity are closely regulated by the metabolic demands of the skeletal muscle. For instance, NAD+ levels link Class III (Sirtuin) enzymatic activity to the energy status of the cell, and starvation or exercise affect Class II HDAC stability and intracellular localization. SUMOylation or phosphorylation of Class II HDACs are modulated by circulating factors, thus establishing a bidirectional link between HDAC activity and endocrine, paracrine, and autocrine factors. Indeed, besides being targets of adipo-myokines, HDACs affect the synthesis of myokines by skeletal muscle, altering the composition of the humoral milieu and ultimately contributing to the muscle functioning as an endocrine organ. In this review, we discuss recent findings on the interplay between HDACs and circulating factors, in relation to skeletal muscle metabolism and its adaptative response to energy demand. We believe that enhancing knowledge on the specific functions of HDACs may have clinical implications leading to the use of improved HDAC inhibitors for the treatment of metabolic syndromes or aging.
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Affiliation(s)
- Alessandra Renzini
- Unit of Histology and Medical Embryology, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy
| | - Marco D’Onghia
- Unit of Histology and Medical Embryology, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy
| | - Dario Coletti
- Unit of Histology and Medical Embryology, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy
- Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Sorbonne Université, Paris, France
| | - Viviana Moresi
- Unit of Histology and Medical Embryology, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy
- Institute of Nanotechnology (Nanotec), National Research Council, Rome, Italy
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12
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It Is High Time Physicians Thought of Natural Products for Alleviating NAFLD. Is There Sufficient Evidence to Use Them? Int J Mol Sci 2021; 22:ijms222413424. [PMID: 34948230 PMCID: PMC8706322 DOI: 10.3390/ijms222413424] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/11/2021] [Accepted: 12/12/2021] [Indexed: 12/19/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease all over the world due to the obesity pandemic; currently, therapeutic options for NAFLD are scarce, except for diet recommendations and physical activity. NAFLD is characterized by excessive accumulation of fat deposits (>5%) in the liver with subsequent inflammation and fibrosis. Studies in the literature show that insulin resistance (IR) may be considered as the key mechanism in the onset and progression of NAFLD. Recently, using natural products as an alternative approach in the treatment of NAFLD has drawn growing attention among physicians. In this review, the authors present the most recent randomized controlled trials (RCTs) and lines of evidence from animal models about the efficacy of nutraceutics in alleviating NAFLD. Among the most studied substances in the literature, the following molecules were chosen because of their presence in the literature of both clinical and preclinical studies: spirulina, oleuropein, garlic, berberine, resveratrol, curcumin, ginseng, glycyrrhizin, coffee, cocoa powder, epigallocatechin-3-gallate, and bromelain.
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13
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Tang X, Cao Y, Arora G, Hwang J, Sajid A, Brown CL, Mehta S, Marín-López A, Chuang YM, Wu MJ, Ma H, Pal U, Narasimhan S, Fikrig E. The Lyme disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector. eLife 2021; 10:e72568. [PMID: 34783654 PMCID: PMC8639152 DOI: 10.7554/elife.72568] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 11/04/2021] [Indexed: 12/24/2022] Open
Abstract
Adiponectin-mediated pathways contribute to mammalian homeostasis; however, little is known about adiponectin and adiponectin receptor signaling in arthropods. In this study, we demonstrate that Ixodes scapularis ticks have an adiponectin receptor-like protein (ISARL) but lack adiponectin, suggesting activation by alternative pathways. ISARL expression is significantly upregulated in the tick gut after Borrelia burgdorferi infection, suggesting that ISARL signaling may be co-opted by the Lyme disease agent. Consistent with this, RNA interference (RNAi)-mediated silencing of ISARL significantly reduced the B. burgdorferi burden in the tick. RNA-seq-based transcriptomics and RNAi assays demonstrate that ISARL-mediated phospholipid metabolism by phosphatidylserine synthase I is associated with B. burgdorferi survival. Furthermore, the tick complement C1q-like protein 3 interacts with ISARL, and B. burgdorferi facilitates this process. This study identifies a new tick metabolic pathway that is connected to the life cycle of the Lyme disease spirochete.
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Affiliation(s)
- Xiaotian Tang
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
| | - Yongguo Cao
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
- Department of Clinical Veterinary Medicine, and Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin UniversityChangchunChina
| | - Gunjan Arora
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
| | - Jesse Hwang
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
| | - Andaleeb Sajid
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
| | - Courtney L Brown
- Yale Combined Program in the Biological and Biomedical Sciences, Yale UniversityNew HavenUnited States
| | - Sameet Mehta
- Yale Center for Genome Analysis, Yale UniversityNew HavenUnited States
| | - Alejandro Marín-López
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
| | - Yu-Min Chuang
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
| | - Ming-Jie Wu
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
| | - Hongwei Ma
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
- Department of Microbiology, School of Basic Medicine, Fourth Military Medical UniversityShaanxiChina
| | - Utpal Pal
- Department of Veterinary Medicine, University of Maryland, College ParkCollege ParkUnited States
| | - Sukanya Narasimhan
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
| | - Erol Fikrig
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale UniversityNew HavenUnited States
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14
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Shklyaev SS, Melnichenko GA, Volevodz NN, Falaleeva NA, Ivanov SA, Kaprin AD, Mokrysheva NG. Adiponectin: a pleiotropic hormone with multifaceted roles. PROBLEMY ENDOKRINOLOGII 2021; 67:98-112. [PMID: 35018766 PMCID: PMC9753852 DOI: 10.14341/probl12827] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 10/22/2021] [Indexed: 05/28/2023]
Abstract
Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to energy storage, metabolic homeostasis, generation of heat, participation in immune functions and secretion of a number of biologically active factors known as adipokines. The most abundant of them is adiponectin. This adipocite-derived hormone exerts pleiotropic actions and exhibits insulin-sensitizing, antidiabetic, anti-obesogenic, anti-inflammatory, antiatherogenic, cardio- and neuroprotective properties. Contrariwise to its protective effects against various pathological events in different cell types, adiponectin may have links to several systemic diseases and malignances. Reduction in adiponectin levels has an implication in COVID-19-associated respiratory failure, which is attributed mainly to a phenomenon called 'adiponectin paradox'. Ample evidence about multiple functions of adiponectin in the body was obtained from animal, mostly rodent studies. Our succinct review is entirely about multifaceted roles of adiponectin and mechanisms of its action in different physiological and pathological states.
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Affiliation(s)
- S. S. Shklyaev
- National Research Center for Endocrinology of the Ministry of Health of the Russian Federation;
A. Tsyb Medical Radiological Research Center — Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
| | - G. A. Melnichenko
- National Research Center for Endocrinology of the Ministry of Health of the Russian Federatio
| | - N. N. Volevodz
- National Research Center for Endocrinology of the Ministry of Health of the Russian Federatio
| | - N. A. Falaleeva
- A. Tsyb Medical Radiological Research Center — Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
| | - S. A. Ivanov
- A. Tsyb Medical Radiological Research Center — Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
| | - A. D. Kaprin
- A. Tsyb Medical Radiological Research Center — Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
| | - N. G. Mokrysheva
- National Research Center for Endocrinology of the Ministry of Health of the Russian Federation
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15
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Ohn J, Been KW, Kim JY, Kim EJ, Park T, Yoon H, Ji JS, Okada‐Iwabu M, Iwabu M, Yamauchi T, Kim YK, Seok C, Kwon O, Kim KH, Lee HH, Chung JH. Discovery of a transdermally deliverable pentapeptide for activating AdipoR1 to promote hair growth. EMBO Mol Med 2021; 13:e13790. [PMID: 34486824 PMCID: PMC8495455 DOI: 10.15252/emmm.202013790] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 07/30/2021] [Accepted: 08/20/2021] [Indexed: 11/09/2022] Open
Abstract
Alopecia induced by aging or side effects of medications affects millions of people worldwide and impairs the quality of life; however, there is a limit to the current medications. Here, we identify a small transdermally deliverable 5-mer peptide (GLYYF; P5) that activates adiponectin receptor 1 (AdipoR1) and promotes hair growth. P5 sufficiently reproduces the biological effect of adiponectin protein via AMPK signaling pathway, increasing the expression of hair growth factors in the dermal papilla cells of human hair follicle. P5 accelerates hair growth ex vivo and induces anagen hair cycle in mice in vivo. Furthermore, we elucidate a key spot for the binding between AdipoR1 and adiponectin protein using docking simulation and mutagenesis studies. This study suggests that P5 could be used as a topical peptide drug for alleviating pathological conditions, which can be improved by adiponectin protein, such as alopecia.
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Affiliation(s)
- Jungyoon Ohn
- Department of Translational MedicineSeoul National University College of MedicineSeoulKorea
- Department of DermatologySeoul National University College of MedicineSeoulKorea
- Department of DermatologySeoul National University HospitalSeoulKorea
- Institute of Human‐Environment Interface BiologySeoul National UniversitySeoulKorea
| | - Kyung Wook Been
- Department of ChemistryCollege of Natural SciencesSeoul National UniversitySeoulKorea
| | - Jin Yong Kim
- Department of DermatologySeoul National University College of MedicineSeoulKorea
- Department of DermatologySeoul National University HospitalSeoulKorea
- Institute of Human‐Environment Interface BiologySeoul National UniversitySeoulKorea
| | - Eun Ju Kim
- Department of DermatologySeoul National University College of MedicineSeoulKorea
- Department of DermatologySeoul National University HospitalSeoulKorea
- Institute of Human‐Environment Interface BiologySeoul National UniversitySeoulKorea
| | - Taeyong Park
- Department of ChemistryCollege of Natural SciencesSeoul National UniversitySeoulKorea
| | - Hye‐Jin Yoon
- Department of ChemistryCollege of Natural SciencesSeoul National UniversitySeoulKorea
| | - Jeong Seok Ji
- Department of ChemistryCollege of Natural SciencesSeoul National UniversitySeoulKorea
| | - Miki Okada‐Iwabu
- Department of Diabetes and Metabolic DiseasesGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Masato Iwabu
- Department of Diabetes and Metabolic DiseasesGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Toshimasa Yamauchi
- Department of Diabetes and Metabolic DiseasesGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Yeon Kyung Kim
- Department of DermatologySeoul National University College of MedicineSeoulKorea
- Department of DermatologySeoul National University HospitalSeoulKorea
- Institute of Human‐Environment Interface BiologySeoul National UniversitySeoulKorea
| | - Chaok Seok
- Department of ChemistryCollege of Natural SciencesSeoul National UniversitySeoulKorea
| | - Ohsang Kwon
- Department of DermatologySeoul National University College of MedicineSeoulKorea
- Department of DermatologySeoul National University HospitalSeoulKorea
- Institute of Human‐Environment Interface BiologySeoul National UniversitySeoulKorea
| | - Kyu Han Kim
- Department of Translational MedicineSeoul National University College of MedicineSeoulKorea
- Department of DermatologySeoul National University College of MedicineSeoulKorea
- Department of DermatologySeoul National University HospitalSeoulKorea
- Institute of Human‐Environment Interface BiologySeoul National UniversitySeoulKorea
| | - Hyung Ho Lee
- Department of ChemistryCollege of Natural SciencesSeoul National UniversitySeoulKorea
| | - Jin Ho Chung
- Department of DermatologySeoul National University College of MedicineSeoulKorea
- Department of DermatologySeoul National University HospitalSeoulKorea
- Institute of Human‐Environment Interface BiologySeoul National UniversitySeoulKorea
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16
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T-Cadherin and the Ratio of Its Ligands as Predictors of Carotid Atherosclerosis: A Pilot Study. Biomedicines 2021; 9:biomedicines9101398. [PMID: 34680515 PMCID: PMC8533356 DOI: 10.3390/biomedicines9101398] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/29/2021] [Accepted: 10/01/2021] [Indexed: 12/27/2022] Open
Abstract
In the cardiovascular system, atherogenic low-density lipoproteins (LDL) and the protective hormone adiponectin bind to the same receptor, T-cadherin. In this study, we tested the hypothesis that the ratio of circulating LDL to high-molecular weight (HMW) adiponectin could predict the development of atherosclerosis. Using enzyme-linked immunosorbent assay, we measured the level of circulating HMW adiponectin in the blood of donors together with ultrasound measuring of intima-media thickness (IMT) of carotid arteries. Single-nucleotide polymorphisms in the T-cadherin gene were identified using polymerase chain reaction. We found that carotid artery IMT is inversely correlated with the level of HMW in male subjects. We also found that the G allele of rs12444338 SNP in the T-cadherin gene correlates with a lower level of circulating T-cadherin and thinner IMT and therefore could be considered as an atheroprotective genotype. Despite our data, we could not provide direct evidence for the initial study hypothesis. However, we did uncover an important correlation between circulating T-cadherin and thinner carotid IMT.
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17
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Zhou Y, Wei LL, Zhang RP, Han CW, Cao Y. Globular adiponectin inhibits osteoblastic differentiation of vascular smooth muscle cells through the PI3K/AKT and Wnt/β-catenin pathway. J Mol Histol 2021; 52:1067-1080. [PMID: 34398360 PMCID: PMC8487883 DOI: 10.1007/s10735-021-10012-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 08/10/2021] [Indexed: 01/20/2023]
Abstract
Lipid metabolism is closely related to the improvement of vascular calcification (VC) in chronic kidney disease (CKD). Globular adiponectin (gAd) has been reported to be involved in the development of VC in CKD, but the detailed regulatory role remains unclear. The present study is aimed to investigate the biological function and the underlying regulation mechanism of gAd in the process of VC during CKD. Vascular smooth muscle cells (VSMCs) calcification was determined by Alizarin Red S staining. Protein signaling related with VC was tested by western blotting. The expression and intracellular localization of runt-related transcription factor 2 (Runx2) was detected by immunofluorescence and uraemic rat with VC was established by a two-step nephrectomy. Combined with the results of Alizarin Red S staining, we discovered that β-glycerophosphate (β-Gp)-induced the osteoblastic differentiation of VSMCs was significantly reversed by gAd treatment. Along with the VSMCs calcification and the increase of Runx2 in β-Gp-exposed VSMCs, the activities of protein kinase B (AKT) and Wnt/β-catenin pathway were enhanced, but that were counteracted by the exposure of gAd in rat and human VSMCs. After administration with agonists of the Wnt (SKL2001) and AKT (SC79), there appeared more osteoblastic differentiation and higher expression of Runx2 in gAd-treated VSMCs, but showing lower impact in the presence of SC79 than that in the presence of SKL2001. In the in vivo experiments, intravenous injection of gAd also significantly inhibited VC and Runx2 level in uraemic rat in a dose-dependent manner, possibly through regulating Wnt/β-catenin pathway. This study demonstrates that gAd ameliorates osteoblastic differentiation of VSMCs possibly by blocking PI3K/AKT and Wnt/β-catenin signaling transduction. The findings provide an important foundation for gAd in treating VC in kidney diseases.
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Affiliation(s)
- Yun Zhou
- Laboratory Medicine, China-Japan Friendship Hospital, No.2 Yinghua Street, Chaoyang District, Beijing, 100029, China
| | - Li-Long Wei
- Laboratory Medicine, China-Japan Friendship Hospital, No.2 Yinghua Street, Chaoyang District, Beijing, 100029, China
| | - Rui-Ping Zhang
- Laboratory Medicine, China-Japan Friendship Hospital, No.2 Yinghua Street, Chaoyang District, Beijing, 100029, China
| | - Cheng-Wu Han
- Laboratory Medicine, China-Japan Friendship Hospital, No.2 Yinghua Street, Chaoyang District, Beijing, 100029, China
| | - Yongtong Cao
- Laboratory Medicine, China-Japan Friendship Hospital, No.2 Yinghua Street, Chaoyang District, Beijing, 100029, China.
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18
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Agostino M, Rooney J, Herat L, Matthews J, Simonds A, Northfield SE, Hopper D, Schlaich MP, Matthews VB. TNFSF14-Derived Molecules as a Novel Treatment for Obesity and Type 2 Diabetes. Int J Mol Sci 2021; 22:ijms221910647. [PMID: 34638990 PMCID: PMC8508965 DOI: 10.3390/ijms221910647] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 09/24/2021] [Accepted: 09/28/2021] [Indexed: 12/12/2022] Open
Abstract
Obesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with glucose intolerance and insulin resistance, often culminating in Type 2 Diabetes (T2D). Importantly, our team has recently shown that the TNF superfamily (TNFSF) member protein, TNFSF14, has been reported to protect against high fat diet induced obesity and pre-diabetes. We hypothesized that mimics of TNFSF14 may therefore be valuable as anti-diabetic agents. In this study, we use in silico approaches to identify key regions of TNFSF14 responsible for binding to the Herpes virus entry mediator and Lymphotoxin β receptor. In vitro evaluation of a selection of optimised peptides identified six potentially therapeutic TNFSF14 peptides. We report that these peptides increased insulin and fatty acid oxidation signalling in skeletal muscle cells. We then selected one of these promising peptides to determine the efficacy to promote metabolic benefits in vivo. Importantly, the TNFSF14 peptide 7 reduced high fat diet-induced glucose intolerance, insulin resistance and hyperinsulinemia in a mouse model of obesity. In addition, we highlight that the TNFSF14 peptide 7 resulted in a marked reduction in liver steatosis and a concomitant increase in phospho-AMPK signalling. We conclude that TNFSF14-derived molecules positively regulate glucose homeostasis and lipid metabolism and may therefore open a completely novel therapeutic pathway for treating obesity and T2D.
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MESH Headings
- Animals
- Binding Sites
- Blood Glucose/metabolism
- Computer Simulation
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/drug therapy
- Diabetes Mellitus, Type 2/etiology
- Diabetes Mellitus, Type 2/metabolism
- Diet, High-Fat/adverse effects
- Disease Models, Animal
- Glucose Intolerance/drug therapy
- Glucose Intolerance/metabolism
- Homeostasis/drug effects
- Hyperinsulinism/drug therapy
- Hyperinsulinism/metabolism
- Hypoglycemic Agents/administration & dosage
- Hypoglycemic Agents/chemical synthesis
- Insulin Resistance
- Lymphotoxin beta Receptor/chemistry
- Lymphotoxin beta Receptor/metabolism
- Male
- Mice
- Mice, Inbred C57BL
- Obesity/complications
- Obesity/drug therapy
- Obesity/etiology
- Obesity/metabolism
- Peptides/administration & dosage
- Peptides/chemical synthesis
- Receptors, Tumor Necrosis Factor, Member 14/chemistry
- Receptors, Tumor Necrosis Factor, Member 14/metabolism
- Signal Transduction/drug effects
- Treatment Outcome
- Tumor Necrosis Factor Ligand Superfamily Member 14/administration & dosage
- Tumor Necrosis Factor Ligand Superfamily Member 14/chemistry
- Tumor Necrosis Factor Ligand Superfamily Member 14/metabolism
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Affiliation(s)
- Mark Agostino
- Curtin Medical School, Curtin University, Bentley, WA 6102, Australia; (M.A.); (A.S.)
- Curtin Health and Innovation Research Institute, Curtin University, Perth, WA 6845, Australia
- Curtin Institute for Computation, Curtin University, Perth, WA 6845, Australia
| | - Jennifer Rooney
- Dobney Hypertension Centre, School of Biomedical Sciences—Royal Perth Hospital Unit, University of Western Australia, Perth, WA 6009, Australia; (J.R.); (L.H.); (J.M.)
| | - Lakshini Herat
- Dobney Hypertension Centre, School of Biomedical Sciences—Royal Perth Hospital Unit, University of Western Australia, Perth, WA 6009, Australia; (J.R.); (L.H.); (J.M.)
| | - Jennifer Matthews
- Dobney Hypertension Centre, School of Biomedical Sciences—Royal Perth Hospital Unit, University of Western Australia, Perth, WA 6009, Australia; (J.R.); (L.H.); (J.M.)
| | - Allyson Simonds
- Curtin Medical School, Curtin University, Bentley, WA 6102, Australia; (M.A.); (A.S.)
| | - Susan E. Northfield
- Department of Biochemistry and Pharmacology, School of Biomedical Sciences, The University of Melbourne, Parkville, VIC 3010, Australia; (S.E.N.); (D.H.)
| | - Denham Hopper
- Department of Biochemistry and Pharmacology, School of Biomedical Sciences, The University of Melbourne, Parkville, VIC 3010, Australia; (S.E.N.); (D.H.)
- School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia
| | - Markus P. Schlaich
- Department of Cardiology, Royal Perth Hospital, Perth, WA 6000, Australia;
- Department of Nephrology, Royal Perth Hospital, Perth, WA 6000, Australia
- Department of Medicine, Royal Perth Hospital, Perth, WA 6000, Australia
| | - Vance B. Matthews
- Dobney Hypertension Centre, School of Biomedical Sciences—Royal Perth Hospital Unit, University of Western Australia, Perth, WA 6009, Australia; (J.R.); (L.H.); (J.M.)
- Correspondence: ; Tel.: +61-8-9224-0239; Fax: +61-8-9224-0374
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The Controversial Role of Adiponectin in Appetite Regulation of Animals. Nutrients 2021; 13:nu13103387. [PMID: 34684387 PMCID: PMC8539471 DOI: 10.3390/nu13103387] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 09/05/2021] [Accepted: 09/23/2021] [Indexed: 12/20/2022] Open
Abstract
Eating disorders and obesity are important health problems with a widespread global epidemic. Adiponectin (AdipoQ), the most abundant adipokine in the plasma, plays important roles in the regulation of energy homeostasis, glucose metabolism and lipid metabolism. Plasma adiponectin concentration is negatively associated with obesity and binge eating disorder. There is a growing interest in the appetite regulation function of adiponectin. However, the effect of AdipoQ on feeding behavior is controversial and closely related to nutritional status and food composition. In this review, we summarize the literatures about the discovery, structure, tissue distribution, receptors and regulation of nutritional status, and focus on the biological function of adiponectin in the regulation of food intake in the central and peripheral system.
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Adiponectin and Asthma: Knowns, Unknowns and Controversies. Int J Mol Sci 2021; 22:ijms22168971. [PMID: 34445677 PMCID: PMC8396527 DOI: 10.3390/ijms22168971] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 08/11/2021] [Accepted: 08/16/2021] [Indexed: 12/14/2022] Open
Abstract
Adiponectin is an adipokine associated with the healthy obese phenotype. Adiponectin increases insulin sensitivity and has cardio and vascular protection actions. Studies related to adiponectin, a modulator of the innate and acquired immunity response, have suggested a role of this molecule in asthma. Studies based on various asthma animal models and on the key cells involved in the allergic response have provided important insights about this relation. Some of them indicated protection and others reversed the balance towards negative effects. Many of them described the cellular pathways activated by adiponectin, which are potentially beneficial for asthma prevention or for reduction in the risk of exacerbations. However, conclusive proofs about their efficiency still need to be provided. In this article, we will, briefly, present the general actions of adiponectin and the epidemiological studies supporting the relation with asthma. The main focus of the current review is on the mechanisms of adiponectin and the impact on the pathobiology of asthma. From this perspective, we will provide arguments for and against the positive influence of this molecule in asthma, also indicating the controversies and sketching out the potential directions of research to complete the picture.
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Howlader M, Sultana MI, Akter F, Hossain MM. Adiponectin gene polymorphisms associated with diabetes mellitus: A descriptive review. Heliyon 2021; 7:e07851. [PMID: 34471717 PMCID: PMC8387910 DOI: 10.1016/j.heliyon.2021.e07851] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 07/17/2021] [Accepted: 08/18/2021] [Indexed: 01/24/2023] Open
Abstract
Diabetes is currently a growing concern of the age. Prevention and treatment of diabetes is a global health priority. Adiponectin is an adipocyte derived protein hormone that enhances insulin sensitivity and ameliorates diabetes by enhancing fatty acid oxidation and glucose uptake in skeletal muscle and reducing glucose production in the liver. Low serum adiponectin concentrations are associated with diabetes, central obesity, insulin resistance and metabolic syndrome. Adiponectin gene is located on chromosome 3q27, where a locus of susceptibility to diabetes was mapped. Several cross-sectional studies showed that single nucleotide polymorphisms (SNPs) in adiponectin gene (ADIPOQ) were associated with diabetes. SNPs in ADIPOQ help in assessing the association of common variants with levels of adiponectin and the risk of diabetes. Two common SNPs, rs2241766 and rs1501299, have been linked significantly to type 1 diabetes mellitus which endow the world with a block of haplotypes. Experimental evidences also suggest that rs1501299, rs2241766, rs266729, rs17366743, rs17300539, rs182052, rs822396, rs17846866, rs3774261 and rs822393 are significantly associated with type 2 diabetes mellitus which is the predominant form of the disease. In addition, rs2241766 and rs266729 are extensively associated with gestational diabetes, a condition that develops in women during pregnancy. Therefore not a particular single mutation but a number of SNPs in adiponectin gene could be a risk factor for developing diabetes among the individuals worldwide. This study firmly suggests that adiponectin plays a crucial role in the pathogenesis of type 1, type 2 and gestational diabetes mellitus.
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Affiliation(s)
- Mithu Howlader
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh
| | - Mst Irin Sultana
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh
| | - Farzana Akter
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh
| | - Md. Murad Hossain
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh
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Fahriani M, Ilmawan M, Fajar JK, Maliga HA, Frediansyah A, Masyeni S, Yusuf H, Nainu F, Rosiello F, Sirinam S, Keam S, Ophinni Y. Persistence of long COVID symptoms in COVID-19 survivors worldwide and its potential pathogenesis - A systematic review and meta-analysis. NARRA J 2021; 1:e36. [PMID: 38449463 PMCID: PMC10914031 DOI: 10.52225/narraj.v1i2.36] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 07/03/2021] [Indexed: 10/16/2023]
Abstract
The study sought to determine the prevalence of persistent long COVID symptoms such as anxiety, depression, dizziness, chest pain, sleep difficulty, palpitations, weight loss, and hair loss among coronavirus disease 2019 (COVID-19) survivors worldwide and to discuss the potential pathogeneses. Potential studies were searched in three databases (PubMed, Scopus, and Web of Science) as of January 30, 2021. Data on study characteristics, patient characteristics during the follow-up, the number of patients with persistent long COVID symptoms and total COVID-19 survivors were collected according to PRISMA guidelines. To assess the quality of studies, the Newcastle-Ottawa scale was used. The estimated prevalence of each long COVID symptom and the association between COVID-19 severity and the occurrence of prolonged symptoms was assessed, if appropriate. The global prevalence of prolonged anxiety was 15.76% (95%CI: 6.36%, 25.15%). Chest pain persisted in 10.36% (239/3,224) of COVID-19 patients (95%CI: 4.92%, 15.80%). Prolonged depression was found in 24 of 548 COVID-19 survivors with an estimated prevalence of 4.32% (95%CI: 2.62%, 6.03%) and dizziness was presented in 4.83% (118/2,219, 95%CI: 1.50%, 8.16%) after recovery. Hair loss was complained by 527 of 2,251 recovered patients (cumulative prevalence of 24.76%, 95%CI: 19.60%, 29.91%), while weight loss was identified in 37 cases among 452 COVID-19 survivors (8.19%, 95%CI: 5.66%, 10.71%). Prolonged palpitation was experienced by 19.38% (211/1,926) survivors with 95%CI: 2.40%, 41.16%. Sleep difficulty was found in 541 of 2,622 COVID-19 survivors (17.87%, 95%CI: 7.55%, 28.20%). The association between COVID-19 severity and the occurrence of persistent long COVID symptoms was not analyzed due to the lack of data. In conclusion, persistent psychological symptoms are frequently reported among COVID-19 survivors. Follow-up studies with a longer duration and larger population are warranted to assess the extent of prolonged symptoms and the quality of life of COVID-19 survivors. Despite various potential pathogeneses that have been hypothesized, a definitive mechanism is yet to be addressed. PROSPERO registration: CRD42021247172.
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Affiliation(s)
- Marhami Fahriani
- Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Aceh, Indonesia
| | - Muhammad Ilmawan
- Faculty of Medicine, Universitas Brawijaya, Malang, East Java, Indonesia
| | - Jonny K. Fajar
- Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Aceh, Indonesia
- Brawijaya Internal Medicine Research Center, Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, Indonesia
| | - Helnida A. Maliga
- Faculty of Medicine, Universitas Brawijaya, Malang, East Java, Indonesia
| | - Andri Frediansyah
- Research Division for Natural Product Technology (BPTBA), Indonesian Institute of Sciences (LIPI), Wonosari, Indonesia
| | - Sri Masyeni
- Department of Internal Medicine, Faculty of Medicine and Health Sciences Universitas Warmadewa, Denpasar, Bali, Indonesia
- Department of Internal Medicine, Sanjiwani Hospital, Denpasar, Bali, Indonesia
| | - Hanifah Yusuf
- Department of Pharmacology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Aceh, Indonesia
| | - Firzan Nainu
- Faculty of Pharmacy, Hasanuddin University, Makassar, South Sulawesi, Indonesia
| | - Francesco Rosiello
- Department of Public Health and Infectious Disease, Sapienza-University of Rome, Rome, Italy
| | - Salin Sirinam
- Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Synat Keam
- School of Medicine, University of Western Australia, Perth, Western Australia, Australia
| | - Youdiil Ophinni
- Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Harvard University, Cambridge, MA, USA
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23
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Sowka A, Dobrzyn P. Role of Perivascular Adipose Tissue-Derived Adiponectin in Vascular Homeostasis. Cells 2021; 10:cells10061485. [PMID: 34204799 PMCID: PMC8231548 DOI: 10.3390/cells10061485] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/04/2021] [Accepted: 06/08/2021] [Indexed: 12/27/2022] Open
Abstract
Studies of adipose tissue biology have demonstrated that adipose tissue should be considered as both passive, energy-storing tissue and an endocrine organ because of the secretion of adipose-specific factors, called adipokines. Adiponectin is a well-described homeostatic adipokine with metabolic properties. It regulates whole-body energy status through the induction of fatty acid oxidation and glucose uptake. Adiponectin also has anti-inflammatory and antidiabetic properties, making it an interesting subject of biomedical studies. Perivascular adipose tissue (PVAT) is a fat depot that is conterminous to the vascular wall and acts on it in a paracrine manner through adipokine secretion. PVAT-derived adiponectin can act on the vascular wall through endothelial cells and vascular smooth muscle cells. The present review describes adiponectin's structure, receptors, and main signaling pathways. We further discuss recent studies of the extent and nature of crosstalk between PVAT-derived adiponectin and endothelial cells, vascular smooth muscle cells, and atherosclerotic plaques. Furthermore, we argue whether adiponectin and its receptors may be considered putative therapeutic targets.
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You J, Sun L, Wang J, Sun F, Wang W, Wang D, Fan X, Liu D, Xu Z, Qiu C, Chen J, Yan H, Liu B. Role of Adiponectin-Notch pathway in cognitive dysfunction associated with depression and in the therapeutic effect of physical exercise. Aging Cell 2021; 20:e13387. [PMID: 34053165 PMCID: PMC8208781 DOI: 10.1111/acel.13387] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 04/22/2021] [Accepted: 05/08/2021] [Indexed: 12/17/2022] Open
Abstract
A substantial percentage of late‐life depression patients also have an cognitive impairment, which severely affects the life quality, while the co‐occurring mechanisms are still unclear. Physical exercise can ameliorate both depressive behaviors and cognitive dysfunction, but the molecular mechanisms underlying its beneficial effects remain elusive. In this study, we uncover a novel adipose tissue to hippocampus crosstalk mediated by Adiponectin‐Notch pathway, with an impact on hippocampal neurogenesis and cognitive function. Adiponectin, an adipocyte‐derived hormone, could activate Notch signaling in the hippocampus through upregulating ADAM10 and Notch1, two key molecules in the Notch signaling. Chronic stress inhibits the Adiponectin‐Notch pathway and induces impaired hippocampal neurogenesis and cognitive dysfunction, which can be rescued by AdipoRon and running. Inhibition Notch signaling by DAPT mimics the adverse effects of chronic stress on hippocampal neurogenesis and cognitive function. Adiponectin knockout mice display depressive‐like behaviors, associated with inhibited Notch signaling, impaired hippocampal neurogenesis and cognitive dysfunction. Physical exercise could activate Adiponectin‐Notch pathway, and improve hippocampal neurogenesis and cognitive function, while deleting adiponectin gene or inhibiting Notch signaling blocks its beneficial effects. Together, our data not only suggest that Adiponectin‐Notch pathway is involved in the pathogenesis of cognitive dysfunction associated with depression, but also contributes to the therapeutic effect of physical exercise. This work helps to decipher the etiology of cognitive impairment associated with depression and hence will provide a potential innovative therapeutic target for these patients.
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Affiliation(s)
- Jingjing You
- Institute for Metabolic & Neuropsychiatric Disorders Binzhou Medical University Hospital Shandong China
| | - Linshan Sun
- Institute for Metabolic & Neuropsychiatric Disorders Binzhou Medical University Hospital Shandong China
| | - Jiangong Wang
- Institute for Metabolic & Neuropsychiatric Disorders Binzhou Medical University Hospital Shandong China
| | - Fengjiao Sun
- Institute for Metabolic & Neuropsychiatric Disorders Binzhou Medical University Hospital Shandong China
| | - Wentao Wang
- Institute for Metabolic & Neuropsychiatric Disorders Binzhou Medical University Hospital Shandong China
| | - Dan Wang
- Institute for Metabolic & Neuropsychiatric Disorders Binzhou Medical University Hospital Shandong China
| | - Xueli Fan
- Department of Neurology Binzhou Medical University Hospital Shandong China
| | - Dunjiang Liu
- Institute for Metabolic & Neuropsychiatric Disorders Binzhou Medical University Hospital Shandong China
| | - Zhicheng Xu
- Institute for Metabolic & Neuropsychiatric Disorders Binzhou Medical University Hospital Shandong China
| | - Changyun Qiu
- Institute for Metabolic & Neuropsychiatric Disorders Binzhou Medical University Hospital Shandong China
| | - Jinbo Chen
- Department of Neurology Binzhou Medical University Hospital Shandong China
| | - Haijing Yan
- Department of Pharmacology College of Basic Medicine Binzhou Medical University Yantai China
| | - Bin Liu
- Institute for Metabolic & Neuropsychiatric Disorders Binzhou Medical University Hospital Shandong China
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25
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Ramos-Ramírez P, Malmhäll C, Tliba O, Rådinger M, Bossios A. Adiponectin/AdipoR1 Axis Promotes IL-10 Release by Human Regulatory T Cells. Front Immunol 2021; 12:677550. [PMID: 34084174 PMCID: PMC8167046 DOI: 10.3389/fimmu.2021.677550] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 04/29/2021] [Indexed: 12/11/2022] Open
Abstract
Background Adiponectin is an important immunomodulatory mediator in inflammatory conditions. While we previously showed that adiponectin receptor 1 (AdipoR1) is expressed in murine regulatory T cells (Tregs), its expression in human Tregs remain unknown. Here, we examined the expression of AdipoR1 in human Tregs and whether its ligand, globular adiponectin (gAd) affects the Treg ability to secrete IL-10 and the role of Type 2 (T2) inflammation in such process. Methods Human Tregs from peripheral blood were analyzed by flow cytometry for AdipoR1, Helios and IL-10 expression. CD4+ T cells enriched from peripheral blood mononuclear cells (PBMCs) were cultured in the presence or the absence of gAd or the chemical adiponectin receptor agonist, AdipoRon, or in a T2 cytokine milieu. Flow cytometry was then used to assess intracellular IL-10, IL-10 secreting cells, FOXP3 and Helios expression, and phosphorylated p38 MAP kinase (MAPK). IL-10 levels in CD4+ T cell supernatants were quantified by ELISA. Results We found that a subset of human Tregs expressed AdipoR1. Importantly, more Helios- cells expressed AdipoR1 than Helios+ cells. Likewise, there was a higher frequency of IL-10+ cells within Helios- AdipoR1+ Tregs compared to Helios+ AdipoR1+ Tregs. In contrast, the IL-10 mean fluorescence intensity (MFI) was higher in Helios+ AdipoR1+ Tregs compared to Helios-AdipoR1+ Tregs. When human CD4+ T cells were treated with gAd or AdipoRon, a significant increase in IL-10 secretion, FOXP3 expression, and p38 MAPK phosphorylation was observed in Helios- AdipoR1+ Tregs. Interestingly, gAd under T2 cytokine milieu significantly increased the intracellular levels of IL-10, mainly in Helios+ AdipoR1+ Tregs, and IL-10 levels in supernatants of CD4+ T cells. Conclusions Collectively, our findings suggest that adiponectin/AdipoR1 axis promotes IL-10 release by Tregs, mainly in Helios- Tregs, and the effect was amplified by T2 inflammation in Helios+ Tregs.
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Affiliation(s)
- Patricia Ramos-Ramírez
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Carina Malmhäll
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Omar Tliba
- Department of Biomedical Sciences, College of Veterinary Medicine, Long Island University, Brookville, NY, United States
| | - Madeleine Rådinger
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Apostolos Bossios
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Huddinge and Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
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26
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Bogdanet D, Reddin C, Murphy D, Doheny HC, Halperin JA, Dunne F, O’Shea PM. Emerging Protein Biomarkers for the Diagnosis or Prediction of Gestational Diabetes-A Scoping Review. J Clin Med 2021; 10:1533. [PMID: 33917484 PMCID: PMC8038821 DOI: 10.3390/jcm10071533] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/02/2021] [Accepted: 04/02/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction: Gestational diabetes (GDM), defined as hyperglycemia with onset or initial recognition during pregnancy, has a rising prevalence paralleling the rise in type 2 diabetes (T2DM) and obesity. GDM is associated with short-term and long-term consequences for both mother and child. Therefore, it is crucial we efficiently identify all cases and initiate early treatment, reducing fetal exposure to hyperglycemia and reducing GDM-related adverse pregnancy outcomes. For this reason, GDM screening is recommended as part of routine pregnancy care. The current screening method, the oral glucose tolerance test (OGTT), is a lengthy, cumbersome and inconvenient test with poor reproducibility. Newer biomarkers that do not necessitate a fasting sample are needed for the prompt diagnosis of GDM. The aim of this scoping review is to highlight and describe emerging protein biomarkers that fulfill these requirements for the diagnosis of GDM. Materials and Methods: This scoping review was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for scoping reviews using Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing & Allied Health Literature (CINAHL), PubMed, Embase and Web of Science with a double screening and extraction process. The search included all articles published in the literature to July 2020. Results: Of the 3519 original database citations identified, 385 were eligible for full-text review. Of these, 332 (86.2%) were included in the scoping review providing a total of 589 biomarkers studied in relation to GDM diagnosis. Given the high number of biomarkers identified, three post hoc criteria were introduced to reduce the items set for discussion: we chose only protein biomarkers with at least five citations in the articles identified by our search and published in the years 2017-2020. When applied, these criteria identified a total of 15 biomarkers, which went forward for review and discussion. Conclusions: This review details protein biomarkers that have been studied to find a suitable test for GDM diagnosis with the potential to replace the OGTT used in current GDM screening protocols. Ongoing research efforts will continue to identify more accurate and practical biomarkers to take GDM screening and diagnosis into the 21st century.
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Affiliation(s)
- Delia Bogdanet
- College of Medicine Nursing and Health Sciences, National University of Ireland Galway, H91TK33 Galway, Ireland;
- Centre for Diabetes Endocrinology and Metabolism, Galway University Hospital, Newcastle Road, H91YR71 Galway, Ireland; (C.R.); (D.M.); (H.C.D.); (P.M.O.)
| | - Catriona Reddin
- Centre for Diabetes Endocrinology and Metabolism, Galway University Hospital, Newcastle Road, H91YR71 Galway, Ireland; (C.R.); (D.M.); (H.C.D.); (P.M.O.)
| | - Dearbhla Murphy
- Centre for Diabetes Endocrinology and Metabolism, Galway University Hospital, Newcastle Road, H91YR71 Galway, Ireland; (C.R.); (D.M.); (H.C.D.); (P.M.O.)
| | - Helen C. Doheny
- Centre for Diabetes Endocrinology and Metabolism, Galway University Hospital, Newcastle Road, H91YR71 Galway, Ireland; (C.R.); (D.M.); (H.C.D.); (P.M.O.)
| | - Jose A. Halperin
- Divisions of Haematology, Brigham & Women’s Hospital, Boston, MA 02115, USA;
| | - Fidelma Dunne
- College of Medicine Nursing and Health Sciences, National University of Ireland Galway, H91TK33 Galway, Ireland;
- Centre for Diabetes Endocrinology and Metabolism, Galway University Hospital, Newcastle Road, H91YR71 Galway, Ireland; (C.R.); (D.M.); (H.C.D.); (P.M.O.)
| | - Paula M. O’Shea
- Centre for Diabetes Endocrinology and Metabolism, Galway University Hospital, Newcastle Road, H91YR71 Galway, Ireland; (C.R.); (D.M.); (H.C.D.); (P.M.O.)
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Adiponectin: Structure, Physiological Functions, Role in Diseases, and Effects of Nutrition. Nutrients 2021; 13:nu13041180. [PMID: 33918360 PMCID: PMC8066826 DOI: 10.3390/nu13041180] [Citation(s) in RCA: 129] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 03/28/2021] [Accepted: 03/29/2021] [Indexed: 12/12/2022] Open
Abstract
Adiponectin (a protein consisting of 244 amino acids and characterized by a molecular weight of 28 kDa) is a cytokine that is secreted from adipose tissues (adipokine). Available evidence suggests that adiponectin is involved in a variety of physiological functions, molecular and cellular events, including lipid metabolism, energy regulation, immune response and inflammation, and insulin sensitivity. It has a protective effect on neurons and neural stem cells. Adiponectin levels have been reported to be negatively correlated with cancer, cardiovascular disease, and diabetes, and shown to be affected (i.e., significantly increased) by proper healthy nutrition. The present review comprehensively overviews the role of adiponectin in a range of diseases, showing that it can be used as a biomarker for diagnosing these disorders as well as a target for monitoring the effectiveness of preventive and treatment interventions.
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28
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Zhou Y, Yang Y, Zhou T, Li B, Wang Z. Adiponectin and Thyroid Cancer: Insight into the Association between Adiponectin and Obesity. Aging Dis 2021; 12:597-613. [PMID: 33815885 PMCID: PMC7990371 DOI: 10.14336/ad.2020.0919] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Accepted: 09/13/2020] [Indexed: 12/14/2022] Open
Abstract
In recent decades, the incidence and diagnosis of thyroid cancer have risen dramatically, and thyroid cancer has now become the most common endocrine cancer in the world. The onset of thyroid cancer is insidious, and its progression is slow and difficult to detect. Therefore, early prevention and treatment have important strategic significance. Moreover, an in-depth exploration of the pathogenesis of thyroid cancer is key to early prevention and treatment. Substantial evidence supports obesity as an independent risk factor for thyroid cancer. Adipose tissue dysfunction in the obese state is accompanied by dysregulation of a variety of adipocytokines. Adiponectin (APN) is one of the most pivotal adipocytokines, and its connection with obesity and obesity-related disease has gradually become a hot topic in research. Recently, the association between APN and thyroid cancer has received increasing attention. The purpose of this review is to systematically review previous studies, give prominence to APN, focus on the relationship between APN, obesity and thyroid cancer, and uncover the underlying pathogenic mechanisms.
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Affiliation(s)
- Yuanyuan Zhou
- 1Department of Endocrinology and Metabolism, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, China.,2Department of Endocrinology and Metabolism, Sixth Affiliated Hospital of Kunming Medical University, The People's Hospital of Yuxi City, Yuxi, China
| | - Ying Yang
- 1Department of Endocrinology and Metabolism, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Taicheng Zhou
- 1Department of Endocrinology and Metabolism, The Second People's Hospital of Yunnan Province, Fourth Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Bai Li
- 3School of Medicine, Yunnan University, Kunming, China
| | - Zhanjian Wang
- 4Department of Endocrinology and Metabolism, The Third Hospital of Hebei Medical University, Shijiazhuang, China
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Association between Single Nucleotide Polymorphism rs9891119 of STAT3 Gene and the Genetic Susceptibility to Type 2 Diabetes in Chinese Han Population from Guangdong. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:6657324. [PMID: 33833859 PMCID: PMC8012137 DOI: 10.1155/2021/6657324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 02/06/2021] [Accepted: 03/12/2021] [Indexed: 11/18/2022]
Abstract
Background The aim of this study was to investigate the association between single nucleotide polymorphism (SNP) rs9891119 of the signal transducer and activator of the transcription 3 (STAT3) gene and genetic susceptibility to type 2 diabetes in Chinese Han population from the Guangdong province. Objective The aim of the present study was to explore the relationship between single nucleotide polymorphism rs9891119 of STAT3 gene and type 2 diabetes mellitus (T2DM), which provides a basis for molecular genetic research on the pathogenesis of T2DM in Chinese Han population. Methods In our case-control study, the SNP rs9891119 was picked out from the STAT3 gene and the SNP genotyping was performed by using the SNPscan™ kit in 1092 patients with type 2 diabetes as cases and 1092 normal persons as controls. The distributions of genotype and allele frequencies in two groups were analyzed by SPSS 20.0 software. Results Our results showed that the alleles of A and C of rs9891119 of the STAT3 gene were 54.3 and 45.7% in patients with type 2 diabetes, while 55.5% and 44.5% in the normal persons, which have no statistical significance (P > 0.05). There were also no significant differences in AA, AC, and CC genotype frequencies between type 2 diabetes patients and normal persons. There were no significant differences in codominant, dominant, recessive, and overdominant genetic models of SNP rs9891119 before and after adjusting the covariant factors (P > 0.05). Conclusions Therefore, genetic susceptibility to type 2 diabetes may be not associated with SNP rs9891119 of the STAT3 gene in Chinese Han population from the Guangdong province.
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The complex role of adipokines in obesity, inflammation, and autoimmunity. Clin Sci (Lond) 2021; 135:731-752. [PMID: 33729498 PMCID: PMC7969664 DOI: 10.1042/cs20200895] [Citation(s) in RCA: 146] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/24/2021] [Accepted: 03/04/2021] [Indexed: 12/12/2022]
Abstract
The global obesity epidemic is a major contributor to chronic disease and disability in the world today. Since the discovery of leptin in 1994, a multitude of studies have characterized the pathological changes that occur within adipose tissue in the obese state. One significant change is the dysregulation of adipokine production. Adipokines are an indispensable link between metabolism and optimal immune system function; however, their dysregulation in obesity contributes to chronic low-grade inflammation and disease pathology. Herein, I will highlight current knowledge on adipokine structure and physiological function, and focus on the known roles of these factors in the modulation of the immune response. I will also discuss adipokines in rheumatic and autoimmune diseases.
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Wang Y, Zheng Y, Li W. Compression loading of osteoclasts attenuated microRNA-146a-5p expression, which promotes angiogenesis by targeting adiponectin. SCIENCE CHINA-LIFE SCIENCES 2021; 65:151-166. [PMID: 33677819 DOI: 10.1007/s11427-020-1869-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 01/06/2021] [Indexed: 11/24/2022]
Abstract
Osteoclastogenesis in alveolar bone induced by compression stress triggers orthodontic tooth movement. Compression stress also stimulates angiogenesis, which is essential for osteoclastogenesis. However, the effects of osteoclastogenesis induced by compression on angiogenesis are poorly understood. In vivo, we found the markers of angiogenesis increased during orthodontic bone remodeling. In vitro, osteoclast-derived exosomes increased proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs), as well as expression of vascular endothelial growth factor and CD31. The promotive effects of exosomes derived from compressed osteoclasts were greater than those derived from osteoclasts without compression. Next, we analyzed changes in the microRNA transcriptome after compression stress and focused on microRNA146a-5p (miR-146a), which was significantly decreased by compression. Transfection of an inhibitor of miR-146a stimulated angiogenesis of HUVECs while miR-146a mimics repressed angiogenesis. Adiponectin (ADP) was confirmed to be a target of miR-146a by dual luciferase reporter assay. In HUVECs treated with exosomes, we detected increased ADP which promoted angiogenesis. Knockdown of ADP in HUVECs reduced the promotive effects of exosomes. Our results demonstrate that the decreased miR-146a observed in osteoclasts after compression promotes angiogenesis by targeting ADP, suggesting a novel method to interfere with bone remodeling induced by compression stress.
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Affiliation(s)
- Yue Wang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China
| | - Yunfei Zheng
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
| | - Weiran Li
- Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
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32
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Heyde I, Begemann K, Oster H. Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism. Endocrinology 2021; 162:6102571. [PMID: 33453099 PMCID: PMC7864004 DOI: 10.1210/endocr/bqab009] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Indexed: 12/17/2022]
Abstract
The term energy metabolism comprises the entirety of chemical processes associated with uptake, conversion, storage, and breakdown of nutrients. All these must be tightly regulated in time and space to ensure metabolic homeostasis in an environment characterized by cycles such as the succession of day and night. Most organisms evolved endogenous circadian clocks to achieve this goal. In mammals, a ubiquitous network of cellular clocks is coordinated by a pacemaker residing in the hypothalamic suprachiasmatic nucleus. Adipocytes harbor their own circadian clocks, and large aspects of adipose physiology are regulated in a circadian manner through transcriptional regulation of clock-controlled genes. White adipose tissue (WAT) stores energy in the form of triglycerides at times of high energy levels that then serve as fuel in times of need. It also functions as an endocrine organ, releasing factors in a circadian manner to regulate food intake and energy turnover in other tissues. Brown adipose tissue (BAT) produces heat through nonshivering thermogenesis, a process also controlled by the circadian clock. We here review how WAT and BAT contribute to the circadian regulation of energy metabolism. We describe how adipose rhythms are regulated by the interplay of systemic signals and local clocks and summarize how adipose-originating circadian factors feed-back on metabolic homeostasis. The role of adipose tissue in the circadian control of metabolism becomes increasingly clear as circadian disruption leads to alterations in adipose tissue regulation, promoting obesity and its sequelae. Stabilizing adipose tissue rhythms, in turn, may help to combat disrupted energy homeostasis and obesity.
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Affiliation(s)
- Isabel Heyde
- Institute of Neurobiology, University of Lübeck, Lübeck, Germany
| | | | - Henrik Oster
- Institute of Neurobiology, University of Lübeck, Lübeck, Germany
- Correspondence: Henrik Oster, PhD, Institute of Neurobiology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.
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Akhigbe R, Ajayi A. The impact of reactive oxygen species in the development of cardiometabolic disorders: a review. Lipids Health Dis 2021; 20:23. [PMID: 33639960 PMCID: PMC7916299 DOI: 10.1186/s12944-021-01435-7] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 01/26/2021] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress, an alteration in the balance between reactive oxygen species (ROS) generation and antioxidant buffering capacity, has been implicated in the pathogenesis of cardiometabolic disorders (CMD). At physiological levels, ROS functions as signalling mediators, regulates various physiological functions such as the growth, proliferation, and migration endothelial cells (EC) and smooth muscle cells (SMC); formation and development of new blood vessels; EC and SMC regulated death; vascular tone; host defence; and genomic stability. However, at excessive levels, it causes a deviation in the redox state, mediates the development of CMD. Multiple mechanisms account for the rise in the production of free radicals in the heart. These include mitochondrial dysfunction and uncoupling, increased fatty acid oxidation, exaggerated activity of nicotinamide adenine dinucleotide phosphate oxidase (NOX), reduced antioxidant capacity, and cardiac metabolic memory. The purpose of this study is to discuss the link between oxidative stress and the aetiopathogenesis of CMD and highlight associated mechanisms. Oxidative stress plays a vital role in the development of obesity and dyslipidaemia, insulin resistance and diabetes, hypertension via various mechanisms associated with ROS-led inflammatory response and endothelial dysfunction.
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Affiliation(s)
- Roland Akhigbe
- Department of Physiology, College of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Oyo State Nigeria
- Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Osun State Nigeria
- Department of Chemical Sciences, Kings University, Odeomu, Osun Nigeria
| | - Ayodeji Ajayi
- Department of Physiology, College of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Oyo State Nigeria
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Lee TH, Christie BR, van Praag H, Lin K, Siu PMF, Xu A, So KF, Yau SY. AdipoRon Treatment Induces a Dose-Dependent Response in Adult Hippocampal Neurogenesis. Int J Mol Sci 2021; 22:2068. [PMID: 33669795 PMCID: PMC7922380 DOI: 10.3390/ijms22042068] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/01/2021] [Accepted: 02/05/2021] [Indexed: 12/28/2022] Open
Abstract
AdipoRon, an adiponectin receptor agonist, elicits similar antidiabetic, anti-atherogenic, and anti-inflammatory effects on mouse models as adiponectin does. Since AdipoRon can cross the blood-brain barrier, its chronic effects on regulating hippocampal function are yet to be examined. This study investigated whether AdipoRon treatment promotes hippocampal neurogenesis and spatial recognition memory in a dose-dependent manner. Adolescent male C57BL/6J mice received continuous treatment of either 20 mg/kg (low dose) or 50 mg/kg (high dose) AdipoRon or vehicle intraperitoneally for 14 days, followed by the open field test to examine anxiety and locomotor activity, and the Y maze test to examine hippocampal-dependent spatial recognition memory. Immunopositive cell markers of neural progenitor cells, immature neurons, and newborn cells in the hippocampal dentate gyrus were quantified. Immunosorbent assays were used to measure the serum levels of factors that can regulate hippocampal neurogenesis, including adiponectin, brain-derived neurotrophic factor (BDNF), and corticosterone. Our results showed that 20 mg/kg AdipoRon treatment significantly promoted hippocampal cell proliferation and increased serum levels of adiponectin and BDNF, though there were no effects on spatial recognition memory and locomotor activity. On the contrary, 50 mg/kg AdipoRon treatment impaired spatial recognition memory, suppressed cell proliferation, neuronal differentiation, and cell survival associated with reduced serum levels of BDNF and adiponectin. The results suggest that a low-dose AdipoRon treatment promotes hippocampal cell proliferation, while a high-dose AdipoRon treatment is detrimental to the hippocampus function.
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Affiliation(s)
- Thomas H. Lee
- Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong;
| | - Brian R. Christie
- Division of Biomedical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada;
| | - Henriette van Praag
- FAU Brain Institute and Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33431, USA;
| | - Kangguang Lin
- Department of Affective Disorder, Guangzhou Brain Hospital, The Brain Affiliated Hospital of Guangzhou Medical University, Guangzhou 510370, China;
| | - Parco Ming-Fai Siu
- Division of Kinesiology, School of Public Health, The University of Hong Kong, Hong Kong;
| | - Aimin Xu
- Department of Medicine, The University of Hong Kong, Hong Kong;
- Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong
- The State Key Laboratory of Pharmacology, The University of Hong Kong, Hong Kong
| | - Kwok-Fai So
- Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China;
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong
- Department of Ophthalmology, The University of Hong Kong, Hong Kong
| | - Suk-yu Yau
- Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong;
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35
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Bertile F, Habold C, Le Maho Y, Giroud S. Body Protein Sparing in Hibernators: A Source for Biomedical Innovation. Front Physiol 2021; 12:634953. [PMID: 33679446 PMCID: PMC7930392 DOI: 10.3389/fphys.2021.634953] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 01/12/2021] [Indexed: 12/11/2022] Open
Abstract
Proteins are not only the major structural components of living cells but also ensure essential physiological functions within the organism. Any change in protein abundance and/or structure is at risk for the proper body functioning and/or survival of organisms. Death following starvation is attributed to a loss of about half of total body proteins, and body protein loss induced by muscle disuse is responsible for major metabolic disorders in immobilized patients, and sedentary or elderly people. Basic knowledge of the molecular and cellular mechanisms that control proteostasis is continuously growing. Yet, finding and developing efficient treatments to limit body/muscle protein loss in humans remain a medical challenge, physical exercise and nutritional programs managing to only partially compensate for it. This is notably a major challenge for the treatment of obesity, where therapies should promote fat loss while preserving body proteins. In this context, hibernating species preserve their lean body mass, including muscles, despite total physical inactivity and low energy consumption during torpor, a state of drastic reduction in metabolic rate associated with a more or less pronounced hypothermia. The present review introduces metabolic, physiological, and behavioral adaptations, e.g., energetics, body temperature, and nutrition, of the torpor or hibernation phenotype from small to large mammals. Hibernating strategies could be linked to allometry aspects, the need for periodic rewarming from torpor, and/or the ability of animals to fast for more or less time, thus determining the capacity of individuals to save proteins. Both fat- and food-storing hibernators rely mostly on their body fat reserves during the torpid state, while minimizing body protein utilization. A number of them may also replenish lost proteins during arousals by consuming food. The review takes stock of the physiological, molecular, and cellular mechanisms that promote body protein and muscle sparing during the inactive state of hibernation. Finally, the review outlines how the detailed understanding of these mechanisms at play in various hibernators is expected to provide innovative solutions to fight human muscle atrophy, to better help the management of obese patients, or to improve the ex vivo preservation of organs.
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Affiliation(s)
- Fabrice Bertile
- University of Strasbourg, CNRS, IPHC UMR 7178, Laboratoire de Spectrométrie de Masse Bio-Organique, Strasbourg, France
| | - Caroline Habold
- University of Strasbourg, CNRS, IPHC UMR 7178, Ecology, Physiology & Ethology Department, Strasbourg, France
| | - Yvon Le Maho
- University of Strasbourg, CNRS, IPHC UMR 7178, Ecology, Physiology & Ethology Department, Strasbourg, France
- Centre Scientifique de Monaco, Monaco, Monaco
| | - Sylvain Giroud
- Research Institute of Wildlife Ecology, Department of Interdisciplinary Life Sciences, University of Veterinary Medicine Vienna, Vienna, Austria
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36
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Karamian M, Moossavi M, Hemmati M. From diabetes to renal aging: the therapeutic potential of adiponectin. J Physiol Biochem 2021; 77:205-214. [PMID: 33555532 DOI: 10.1007/s13105-021-00790-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Accepted: 01/14/2021] [Indexed: 12/11/2022]
Abstract
Nowadays, the complications related to diabetes, such as nephropathy, cardiovascular problems, and aging, are highly being considered. Renal cell aging is affected by various mechanisms of inflammation, oxidative stress, and basement membrane thickening, which are significant causes of renal dysfunction in diabetes. Due to recent studies, adiponectin plays a key role in diabetes-related kidney diseases as a fat-derived hormone. In diabetes, reduced adiponectin levels are associated to renal cell aging. Oxidative stress and related signaling pathways are the main routes in which adiponectin may be effective to decline diabetes-associated aging. Therefore, adiponectin signaling in target tissues becomes one of the research areas of interest in metabolism and clinical medicine. Studies on adiponectin signaling will increase our understanding of adiponectin role in diabetes-linked diseases as well as shortening life span conditions which may guide the design of antidiabetic and anti-aging drugs.
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Affiliation(s)
- Mehdi Karamian
- Department of Parasitology and Mycology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Maryam Moossavi
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Mina Hemmati
- Department of Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
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Wilhelmsen A, Tsintzas K, Jones SW. Recent advances and future avenues in understanding the role of adipose tissue cross talk in mediating skeletal muscle mass and function with ageing. GeroScience 2021; 43:85-110. [PMID: 33528828 PMCID: PMC8050140 DOI: 10.1007/s11357-021-00322-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 01/01/2021] [Indexed: 12/15/2022] Open
Abstract
Sarcopenia, broadly defined as the age-related decline in skeletal muscle mass, quality, and function, is associated with chronic low-grade inflammation and an increased likelihood of adverse health outcomes. The regulation of skeletal muscle mass with ageing is complex and necessitates a delicate balance between muscle protein synthesis and degradation. The secretion and transfer of cytokines, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), both discretely and within extracellular vesicles, have emerged as important communication channels between tissues. Some of these factors have been implicated in regulating skeletal muscle mass, function, and pathologies and may be perturbed by excessive adiposity. Indeed, adipose tissue participates in a broad spectrum of inter-organ communication and obesity promotes the accumulation of macrophages, cellular senescence, and the production and secretion of pro-inflammatory factors. Pertinently, age-related sarcopenia has been reported to be more prevalent in obesity; however, such effects are confounded by comorbidities and physical activity level. In this review, we provide evidence that adiposity may exacerbate age-related sarcopenia and outline some emerging concepts of adipose-skeletal muscle communication including the secretion and processing of novel myokines and adipokines and the role of extracellular vesicles in mediating inter-tissue cross talk via lncRNAs and miRNAs in the context of sarcopenia, ageing, and obesity. Further research using advances in proteomics, transcriptomics, and techniques to investigate extracellular vesicles, with an emphasis on translational, longitudinal human studies, is required to better understand the physiological significance of these factors, the impact of obesity upon them, and their potential as therapeutic targets in combating muscle wasting.
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Affiliation(s)
- Andrew Wilhelmsen
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Kostas Tsintzas
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
| | - Simon W Jones
- Institute of Inflammation and Ageing, MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, Queen Elizabeth Hospital, The University of Birmingham, Birmingham, UK
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38
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Pheiffer C, Dias S, Jack B, Malaza N, Adam S. Adiponectin as a Potential Biomarker for Pregnancy Disorders. Int J Mol Sci 2021; 22:1326. [PMID: 33572712 PMCID: PMC7866110 DOI: 10.3390/ijms22031326] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 12/28/2020] [Accepted: 01/06/2021] [Indexed: 12/13/2022] Open
Abstract
Adiponectin is an adipocyte-derived hormone that plays a critical role in energy homeostasis, mainly attributed to its insulin-sensitizing properties. Accumulating studies have reported that adiponectin concentrations are decreased during metabolic diseases, such as obesity and type 2 diabetes, with an emerging body of evidence providing support for its use as a biomarker for pregnancy complications. The identification of maternal factors that could predict the outcome of compromised pregnancies could act as valuable tools that allow the early recognition of high-risk pregnancies, facilitating close follow-up and prevention of pregnancy complications in mother and child. In this review we consider the role of adiponectin as a potential biomarker of disorders associated with pregnancy. We discuss common disorders associated with pregnancy (gestational diabetes mellitus, preeclampsia, preterm birth and abnormal intrauterine growth) and highlight studies that have investigated the potential of adiponectin to serve as biomarkers for these disorders. We conclude the review by recommending strategies to consider for future research.
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Affiliation(s)
- Carmen Pheiffer
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, P.O. Box 19070, Tygerberg, Cape Town 7505, South Africa; (S.D.); (B.J.); (N.M.)
- Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg, Cape Town 7505, South Africa
| | - Stephanie Dias
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, P.O. Box 19070, Tygerberg, Cape Town 7505, South Africa; (S.D.); (B.J.); (N.M.)
| | - Babalwa Jack
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, P.O. Box 19070, Tygerberg, Cape Town 7505, South Africa; (S.D.); (B.J.); (N.M.)
| | - Nompumelelo Malaza
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, P.O. Box 19070, Tygerberg, Cape Town 7505, South Africa; (S.D.); (B.J.); (N.M.)
- Department of Reproductive Biology, University of Pretoria, Private Bag X169, Pretoria 0001, South Africa
| | - Sumaiya Adam
- Department of Obstetrics and Gynaecology, University of Pretoria, Private Bag X169, Pretoria 0001, South Africa;
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Giroud S, Habold C, Nespolo RF, Mejías C, Terrien J, Logan SM, Henning RH, Storey KB. The Torpid State: Recent Advances in Metabolic Adaptations and Protective Mechanisms †. Front Physiol 2021; 11:623665. [PMID: 33551846 PMCID: PMC7854925 DOI: 10.3389/fphys.2020.623665] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 12/21/2020] [Indexed: 12/18/2022] Open
Abstract
Torpor and hibernation are powerful strategies enabling animals to survive periods of low resource availability. The state of torpor results from an active and drastic reduction of an individual's metabolic rate (MR) associated with a relatively pronounced decrease in body temperature. To date, several forms of torpor have been described in all three mammalian subclasses, i.e., monotremes, marsupials, and placentals, as well as in a few avian orders. This review highlights some of the characteristics, from the whole organism down to cellular and molecular aspects, associated with the torpor phenotype. The first part of this review focuses on the specific metabolic adaptations of torpor, as it is used by many species from temperate zones. This notably includes the endocrine changes involved in fat- and food-storing hibernating species, explaining biomedical implications of MR depression. We further compare adaptive mechanisms occurring in opportunistic vs. seasonal heterotherms, such as tropical and sub-tropical species. Such comparisons bring new insights into the metabolic origins of hibernation among tropical species, including resistance mechanisms to oxidative stress. The second section of this review emphasizes the mechanisms enabling heterotherms to protect their key organs against potential threats, such as reactive oxygen species, associated with the torpid state. We notably address the mechanisms of cellular rehabilitation and protection during torpor and hibernation, with an emphasis on the brain, a central organ requiring protection during torpor and recovery. Also, a special focus is given to the role of an ubiquitous and readily-diffusing molecule, hydrogen sulfide (H2S), in protecting against ischemia-reperfusion damage in various organs over the torpor-arousal cycle and during the torpid state. We conclude that (i) the flexibility of torpor use as an adaptive strategy enables different heterothermic species to substantially suppress their energy needs during periods of severely reduced food availability, (ii) the torpor phenotype implies marked metabolic adaptations from the whole organism down to cellular and molecular levels, and (iii) the torpid state is associated with highly efficient rehabilitation and protective mechanisms ensuring the continuity of proper bodily functions. Comparison of mechanisms in monotremes and marsupials is warranted for understanding the origin and evolution of mammalian torpor.
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Affiliation(s)
- Sylvain Giroud
- Research Institute of Wildlife Ecology, Department of Interdisciplinary Life Sciences, University of Veterinary Medicine, Vienna, Austria
| | - Caroline Habold
- University of Strasbourg, CNRS, IPHC, UMR 7178, Strasbourg, France
| | - Roberto F. Nespolo
- Instituto de Ciencias Ambientales y Evolutivas, Universidad Austral de Chile, ANID – Millennium Science Initiative Program-iBio, Valdivia, Chile
- Center of Applied Ecology and Sustainability, Departamento de Ecología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Carlos Mejías
- Instituto de Ciencias Ambientales y Evolutivas, Universidad Austral de Chile, ANID – Millennium Science Initiative Program-iBio, Valdivia, Chile
- Center of Applied Ecology and Sustainability, Departamento de Ecología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jérémy Terrien
- Unité Mécanismes Adaptatifs et Evolution (MECADEV), UMR 7179, CNRS, Muséum National d’Histoire Naturelle, Brunoy, France
| | | | - Robert H. Henning
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, Netherlands
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Chen YJ, Lin CW, Peng YJ, Huang CW, Chien YS, Huang TH, Liao PX, Yang WY, Wang MH, Mersmann HJ, Wu SC, Chuang TY, Lin YY, Kuo WH, Ding ST. Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice. Int J Mol Sci 2021; 22:ijms22020906. [PMID: 33477525 PMCID: PMC7831094 DOI: 10.3390/ijms22020906] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/12/2021] [Accepted: 01/15/2021] [Indexed: 01/05/2023] Open
Abstract
Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing “healthy obese” by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. Here, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [18F] fluorodeoxyglucose-PET/CT (18F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression, related to thermogenic Ucp1, BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation, and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic Ucp1, BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis.
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MESH Headings
- Adipocytes, Beige/metabolism
- Adipose Tissue, Beige/diagnostic imaging
- Adipose Tissue, Beige/metabolism
- Adipose Tissue, Brown/diagnostic imaging
- Adipose Tissue, Brown/metabolism
- Adipose Tissue, White/diagnostic imaging
- Adipose Tissue, White/metabolism
- Animals
- Energy Metabolism/genetics
- Gene Expression Regulation, Developmental/genetics
- Mice
- Mice, Transgenic/genetics
- Mice, Transgenic/metabolism
- Mitochondria/genetics
- Obesity/genetics
- Obesity/metabolism
- Obesity/pathology
- Positron-Emission Tomography
- Receptors, Adiponectin/genetics
- Thermogenesis/genetics
- Uncoupling Protein 1/genetics
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Affiliation(s)
- Yu-Jen Chen
- Institute of Biotechnology, National Taiwan University, Taipei 10617, Taiwan; (C.-W.L.); (S.-C.W.)
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
- Correspondence: (Y.-J.C.); (Y.-Y.L.); (W.-H.K.); (S.-T.D.); Tel.: +886-2-3366-4175 (S.-T.D.)
| | - Chiao-Wei Lin
- Institute of Biotechnology, National Taiwan University, Taipei 10617, Taiwan; (C.-W.L.); (S.-C.W.)
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
| | - Yu-Ju Peng
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
| | - Chao-Wei Huang
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
| | - Yi-Shan Chien
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
| | - Tzu-Hsuan Huang
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
| | - Pei-Xin Liao
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
| | - Wen-Yuan Yang
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
| | - Mei-Hui Wang
- Institute of Nuclear Energy Research, Taoyuan 325, Taiwan;
| | - Harry J. Mersmann
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
| | - Shinn-Chih Wu
- Institute of Biotechnology, National Taiwan University, Taipei 10617, Taiwan; (C.-W.L.); (S.-C.W.)
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
| | - Tai-Yuan Chuang
- Department of Athletics, National Taiwan University, Taipei 10617, Taiwan;
| | - Yuan-Yu Lin
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
- Correspondence: (Y.-J.C.); (Y.-Y.L.); (W.-H.K.); (S.-T.D.); Tel.: +886-2-3366-4175 (S.-T.D.)
| | - Wen-Hung Kuo
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10617, Taiwan
- Correspondence: (Y.-J.C.); (Y.-Y.L.); (W.-H.K.); (S.-T.D.); Tel.: +886-2-3366-4175 (S.-T.D.)
| | - Shih-Torng Ding
- Institute of Biotechnology, National Taiwan University, Taipei 10617, Taiwan; (C.-W.L.); (S.-C.W.)
- Department of Animal Science and Technology, National Taiwan University, Taipei 10617, Taiwan; (Y.-J.P.); (C.-W.H.); (Y.-S.C.); (T.-H.H.); (P.-X.L.); (W.-Y.Y.); (H.J.M.)
- Correspondence: (Y.-J.C.); (Y.-Y.L.); (W.-H.K.); (S.-T.D.); Tel.: +886-2-3366-4175 (S.-T.D.)
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Lee IK, Kim G, Kim DH, Kim BB. PEG-BHD1028 Peptide Regulates Insulin Resistance and Fatty Acid β-Oxidation, and Mitochondrial Biogenesis by Binding to Two Heterogeneous Binding Sites of Adiponectin Receptors, AdipoR1 and AdipoR2. Int J Mol Sci 2021; 22:ijms22020884. [PMID: 33477324 PMCID: PMC7830917 DOI: 10.3390/ijms22020884] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/12/2021] [Accepted: 01/14/2021] [Indexed: 12/17/2022] Open
Abstract
Adiponectin plays multiple critical roles in modulating various physiological processes by binding to its receptors. The functions of PEG-BHD1028, a potent novel peptide agonist to AdipoRs, was evaluated using in vitro and in vivo models based on the reported action spectrum of adiponectin. To confirm the design concept of PEG-BHD1028, the binding sites and their affinities were analyzed using the SPR (Surface Plasmon Resonance) assay. The results revealed that PEG-BHD1028 was bound to two heterogeneous binding sites of AdipoR1 and AdipoR2 with a relatively high affinity. In C2C12 cells, PEG-BHD1028 significantly activated AMPK and subsequent pathways and enhanced fatty acid β-oxidation and mitochondrial biogenesis. Furthermore, it also facilitated glucose uptake by lowering insulin resistance in insulin-resistant C2C12 cells. PEG-BHD1028 significantly reduced the fasting plasma glucose level in db/db mice following a single s.c. injection of 50, 100, and 200 μg/Kg and glucose tolerance at a dose of 50 μg/Kg with significantly decreased insulin production. The animals received 5, 25, and 50 μg/Kg of PEG-BHD1028 for 21 days significantly lost their weight after 18 days in a range of 5-7%. These results imply the development of PEG-BHD1028 as a potential adiponectin replacement therapeutic agent.
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Affiliation(s)
| | | | | | - Brian B. Kim
- Correspondence: ; Tel.: +82-31-360-3132; Fax: +82-31-360-3133
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Shi X, Zhu S, Jin H, Fang J, Xing X, Wang Y, Wang H, Wang C, Niu T, Liu K. The Anti-Inflammatory Effect of KS23, A Novel Peptide Derived From Globular Adiponectin, on Endotoxin-Induced Uveitis in Rats. Front Pharmacol 2021; 11:585446. [PMID: 33510636 PMCID: PMC7835799 DOI: 10.3389/fphar.2020.585446] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/24/2020] [Indexed: 12/30/2022] Open
Abstract
Purpose: Adiponectin has been shown to exert potent anti-inflammatory activities in a range of systemic inflammatory diseases. This study aimed to investigate the potential therapeutic effects of KS23, a globular adiponectin-derived peptide, on endotoxin-induced uveitis (EIU) in rats and lipopolysaccharide (LPS)-stimulated mouse macrophage-like RAW 264.7 cells. Methods: EIU was induced in Lewis rats by subcutaneous injection of LPS into a single footpad. KS23 or phosphate-buffered saline (PBS) was administered immediately after LPS induction via intravitreal injection. Twenty-four hours later, clinical and histopathological scores were evaluated, and the aqueous humor (AqH) was collected to determine the infiltrating cells, protein concentration, and levels of inflammatory cytokines. In vitro, cultured RAW 264.7 cells were stimulated with LPS in the presence or absence of KS23, inflammatory cytokine levels in the supernatant, nuclear translocation of nuclear factor kappa B (NF-κB) subunit p65, and the expression of NF-kB signaling pathway components were analyzed. Results: KS23 treatment significantly ameliorated the clinical and histopathological scores of EIU rats and reduced the levels of infiltration cells, protein, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the aqueous humor. Consistently, KS23 decreased the expression of TNF-α and IL-6 in the supernatant of LPS-stimulated RAW 264.7 cells and inhibited the LPS-induced nuclear translocation of NF-κB p65 and the phosphorylation of IKKα/β/IκBα/NF-κB. Conclusion: The in vivo and in vitro results demonstrated the anti-inflammatory effects of the peptide KS23 and suggested that KS23 is a compelling, novel therapeutic candidate for the treatment of ocular inflammation.
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Affiliation(s)
- Xin Shi
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Shaopin Zhu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Huiyi Jin
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Junwei Fang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Xindan Xing
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Yihan Wang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Hanying Wang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Chingyi Wang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Tian Niu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Kun Liu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
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AdipoR agonist increases insulin sensitivity and exercise endurance in AdipoR-humanized mice. Commun Biol 2021; 4:45. [PMID: 33420419 PMCID: PMC7794315 DOI: 10.1038/s42003-020-01579-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Accepted: 12/09/2020] [Indexed: 12/25/2022] Open
Abstract
Adiponectin receptors, AdipoR1 and AdipoR2 exert anti-diabetic effects. Although muscle-specific disruption of AdipoR1 has been shown to result in decreased insulin sensitivity and decreased exercise endurance, it remains to be determined whether upregulation of AdipoR1 could reverse them in obese diabetic mice. Here, we show that muscle-specific expression of human AdipoR1 increased expression levels of genes involved in mitochondrial biogenesis and oxidative stress-detoxification to almost the same extents as treadmill exercise, and concomitantly increased insulin sensitivity and exercise endurance in obese diabetic mice. Moreover, we created AdipoR-humanized mice which express human AdipoR1 in muscle of AdipoR1·R2 double-knockout mice. Most importantly, the small-molecule AdipoR agonist AdipoRon could exert its beneficial effects in muscle via human AdipoR, and increased insulin sensitivity and exercise endurance in AdipoR-humanized mice. This study suggests that expression of human AdipoR1 in skeletal muscle could be exercise-mimetics, and that AdipoRon could exert its beneficial effects via human AdipoR1. Masato Iwabu and Miki Okada-Iwabu et al. investigate whether diabetic phenotypes associated with disruption of the adiponectin receptor (AdipoR1) can be reversed in diabetic mice by upregulation of the receptor. They show that overexpressing human AdipoR1 in the muscles of diabetic mice increased insulin sensitivity and exercise endurance, suggesting a possible route for future clinical therapies.
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44
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Lewis JW, Edwards JR, Naylor AJ, McGettrick HM. Adiponectin signalling in bone homeostasis, with age and in disease. Bone Res 2021; 9:1. [PMID: 33414405 PMCID: PMC7790832 DOI: 10.1038/s41413-020-00122-0] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 08/28/2020] [Accepted: 10/14/2020] [Indexed: 01/29/2023] Open
Abstract
Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin resistance. Within the bone, osteoblasts and osteoclasts express the adiponectin receptors, however, there are conflicting reports on the effects of adiponectin on bone formation and turnover. Many studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro: with increased osteoblast differentiation and activity, alongside lower levels of osteoclastogenesis. However, human studies often demonstrate an inverse relationship between adiponectin concentration and bone activity. Moreover, the presence of multiple isoforms of adiponectin and multiple receptor subtypes has the potential to lead to more complex signalling and functional consequences. As such, we still do not fully understand the importance of the adiponectin signalling pathway in regulating bone homeostasis and repair in health, with age and in disease. In this review, we explore our current understanding of adiponectin bioactivity in the bone; the significance of its different isoforms; and how adiponectin biology is altered in disease. Ultimately, furthering our understanding of adiponectin regulation of bone biology is key to developing pharmacological and non-pharmacological (lifestyle) interventions that target adiponectin signalling to boost bone growth and repair in healthy ageing, following injury or in disease.
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Affiliation(s)
- Jonathan W Lewis
- Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK
| | - James R Edwards
- Ageing & Regeneration Research Group, Botnar Research Centre, University of Oxford, Oxford, OX3 7LD, UK
| | - Amy J Naylor
- Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK
| | - Helen M McGettrick
- Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK.
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45
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Horikawa T, Hiramoto K, Goto K, Sekijima H, Ooi K. Differences in the mechanism of type 1 and type 2 diabetes-induced skin dryness by using model mice. Int J Med Sci 2021; 18:474-481. [PMID: 33390816 PMCID: PMC7757134 DOI: 10.7150/ijms.50764] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 11/03/2020] [Indexed: 12/20/2022] Open
Abstract
Diabetes induces dry skin that may cause infective diseases. In this study, we aimed to clarify the mechanism of diabetes-induced skin dryness in animal models. We also examined the difference in the mechanism of skin dryness in type 1 and type 2 diabetes. We examined skin dryness in type 1 diabetes model mice (streptozotocin [STZ] induction), non-obesity type 2 diabetes model mice (newborn STZ injection), and obesity type 2 diabetes model mice (KK-Ay/TaJcl). An increase in transepidermal water loss was observed in the type 1 diabetes model mice, and reduced skin hydration was observed in the type 2 diabetes model mice. In the type 1 diabetes model mice, an increase in advanced glycation end products and matrix metalloproteinase-9 led to a decline in collagen IV level, inducing skin dryness. In the obesity type 2 diabetes model mice, an increase in the release of histamine and hyaluronidase by mast cells resulted in a decline in the level of hyaluronic acid, inducing skin dryness. However, in the non-obesity type 2 diabetes model mice, the main factors of skin dryness could not be clearly identified. Nevertheless, inflammatory cytokine levels increased. We hypothesize that inflammatory cytokines disrupt the collagen of the skin. Diabetes caused skin dryness in each mouse model, and the mechanism of skin dryness differed by diabetes type.
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Affiliation(s)
- Tsuneki Horikawa
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan
| | - Keiichi Hiramoto
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan
| | - Kenji Goto
- Research Laboratories, Nichinichi Pharmaceutical Co., Ltd., Iga, Japan
| | - Hidehisa Sekijima
- Department of Forensic Medicine and Sciences, Graduate School of Medicine, Mie University, Tsu, Japan
| | - Kazuya Ooi
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan
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46
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Li C, Meng F, Garza JC, Liu J, Lei Y, Kirov SA, Guo M, Lu XY. Modulation of depression-related behaviors by adiponectin AdipoR1 receptors in 5-HT neurons. Mol Psychiatry 2021; 26:4205-4220. [PMID: 31980728 PMCID: PMC7377958 DOI: 10.1038/s41380-020-0649-0] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 12/20/2019] [Accepted: 01/10/2020] [Indexed: 01/17/2023]
Abstract
The adipocyte-derived hormone adiponectin has a broad spectrum of functions beyond metabolic control. We previously reported that adiponectin acts in the brain to regulate depression-related behaviors. However, its underlying neural substrates have not been identified. Here we show that adiponectin receptor 1 (AdipoR1) is expressed in the dorsal raphe nucleus (DRN) and colocalized with tryptophan hydroxylase 2 (TPH2), a marker of serotonin (5-HT) neurons. Selective deletion of AdipoR1 in 5-HT neurons induced anhedonia in male mice, as indicated by reduced female urine sniffing time and saccharin preference, and behavioral despair in female mice and enhanced stress-induced decrease in sucrose preference in both sexes. The expression levels of TPH2 were downregulated with a concurrent reduction of 5-HT-immunoreactivity in the DRN and its two major projection regions, the hippocampus and medial prefrontal cortex (mPFC), in male but not female mice lacking AdipoR1 in 5-HT neurons. In addition, serotonin transporter (SERT) expression was upregulated in both DRN projection fields of male mice but only in the mPFC of female mice. These changes presumably lead to decreased 5-HT synthesis and/or increased 5-HT reuptake, thereby reducing 5-HT transmission. The augmented behavioral responses to the selective serotonin reuptake inhibitor fluoxetine but not desipramine, a selective norepinephrine reuptake inhibitor, observed in conditional knockout male mice supports deficient 5-HT transmission underlying depression-related phenotypes. Our results indicate that adiponectin acts on 5-HT neurons through AdipoR1 receptors to regulate depression-related behaviors in a sex-dependent manner.
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Affiliation(s)
- Chen Li
- Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong, China. .,Department of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.
| | - Fantao Meng
- grid.452240.5Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong China
| | - Jacob C. Garza
- grid.410427.40000 0001 2284 9329Department of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA USA ,grid.38142.3c000000041936754XPresent Address: Center for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA
| | - Jing Liu
- grid.452240.5Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong China
| | - Yun Lei
- grid.410427.40000 0001 2284 9329Department of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA USA
| | - Sergei A. Kirov
- grid.410427.40000 0001 2284 9329Department of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA USA
| | - Ming Guo
- grid.452240.5Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong China ,grid.410427.40000 0001 2284 9329Department of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA USA
| | - Xin-Yun Lu
- Department of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.
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47
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Da Eira D, Jani S, Sung H, Sweeney G, Ceddia RB. Effects of the adiponectin mimetic compound ALY688 on glucose and fat metabolism in visceral and subcutaneous rat adipocytes. Adipocyte 2020; 9:550-562. [PMID: 32897149 PMCID: PMC7714433 DOI: 10.1080/21623945.2020.1817230] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Adiponectin regulates white adipose tissue (WAT) metabolism and promotes insulin-sensitizing and anti-atherosclerotic effects in vivo. In this context, small molecule adiponectin receptor agonists have become of great therapeutic value for the treatment of metabolic diseases. Here, we investigated the effects of the adiponectin mimetic compound ALY688 on WAT metabolism. To accomplish this, rat epididymal (Epid) and subcutaneous inguinal (Sc Ing) adipocytes were isolated and incubated with ALY688. Subsequently, several parameters of glucose and fat metabolism were assessed. ALY688 promoted AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, enhanced glucose oxidation, and suppressed fat oxidation in adipocytes from both fat depots. ALY688 did not affect basal and insulin-stimulated rates of glucose uptake, glucose incorporation into lipids, and AKTSer473 and p38 mitogen-activated protein kinase (MAPK) phosphorylations in either Epid or Sc Ing adipocytes. ALY688 did not alter basal lipolysis in Epid and Sc Ing adipocytes, but it enhanced isoproterenol-induced lipolysis in Epid adipocytes. Adiponectin receptor 2 (AdipoR2) mRNA was the prevalent isoform expressed in all adipocytes, and Epid adipocytes displayed significantly higher AdipoR2 mRNA expression than Sc Ing adipocytes. In conclusion, ALY688 can regulate adiposity and affect glycaemic control by altering substrate portioning in the WAT in a fat depot-specific manner.
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Affiliation(s)
- Daniel Da Eira
- School of Kinesiology and Health Science, York University, North York, Canada
| | - Shailee Jani
- School of Kinesiology and Health Science, York University, North York, Canada
| | - Hyekyoung Sung
- Department of Biology, York University, North York, Canada
| | - Gary Sweeney
- Department of Biology, York University, North York, Canada
| | - Rolando B. Ceddia
- School of Kinesiology and Health Science, York University, North York, Canada
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48
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Xu H, Zhao Q, Song N, Yan Z, Lin R, Wu S, Jiang L, Hong S, Xie J, Zhou H, Wang R, Jiang X. AdipoR1/AdipoR2 dual agonist recovers nonalcoholic steatohepatitis and related fibrosis via endoplasmic reticulum-mitochondria axis. Nat Commun 2020; 11:5807. [PMID: 33199780 PMCID: PMC7669869 DOI: 10.1038/s41467-020-19668-y] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Accepted: 10/27/2020] [Indexed: 12/13/2022] Open
Abstract
Chronic nonalcoholic steatohepatitis (NASH) is a metabolic disorder that often leads to liver fibrosis, a condition with limited therapy options. Adiponectin is an adipocytokine that regulates glucose and lipid metabolism via binding to its receptors AdipoR1 and AdipoR2, and AdipoRs signaling is reported to enhance fatty acid oxidation and glucose uptake. Here, we synthesize and report an adiponectin-based agonist JT003, which potently improves insulin resistance in high fat diet induced NASH mice and suppresses hepatic stellate cells (HSCs) activation in CCl4 induced liver fibrosis. Mechanistic studies indicate that JT003 simultaneously stimulates AdipoR1- and AdipoR2- mediated signaling pathways as well as the PI3K-Akt pathway. Moreover, JT003 treatment significantly improves ER-mitochondrial axis function, which contributes to the reduced HSCs activation. Thus, the AdipoR1/AdipoR2 dual agonist improves both NASH and fibrosis in mice models, which provides the pharmacological and biological foundation for developing AdipoRs-based therapeutic agents on liver fibrosis. Nonalcoholic steatohepatitis (NASH) and associated liver fibrosis have limited therapy options. Here the authors report a novel adiponectin-based dual agonist for adiponectin receptors 1 and 2 with a longer half-life, and show that it ameliorates NASH and liver fibrosis in mouse models.
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Affiliation(s)
- Hongjiao Xu
- School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Outer Ring Road, Guangzhou, 510006, China
| | - Qian Zhao
- School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Outer Ring Road, Guangzhou, 510006, China
| | - Nazi Song
- School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Outer Ring Road, Guangzhou, 510006, China
| | - Zhibin Yan
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Runfeng Lin
- School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Outer Ring Road, Guangzhou, 510006, China
| | - Shuohan Wu
- School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Outer Ring Road, Guangzhou, 510006, China
| | - Lili Jiang
- School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Outer Ring Road, Guangzhou, 510006, China
| | - Sihua Hong
- School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Outer Ring Road, Guangzhou, 510006, China
| | - Junqiu Xie
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Huihao Zhou
- School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Outer Ring Road, Guangzhou, 510006, China
| | - Rui Wang
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Xianxing Jiang
- School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Outer Ring Road, Guangzhou, 510006, China.
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49
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Afzal S, Abdul Sattar M, Johns EJ, Eseyin OA. Renoprotective and haemodynamic effects of adiponectin and peroxisome proliferator-activated receptor agonist, pioglitazone, in renal vasculature of diabetic Spontaneously hypertensive rats. PLoS One 2020; 15:e0229803. [PMID: 33170841 PMCID: PMC7654782 DOI: 10.1371/journal.pone.0229803] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 10/14/2020] [Indexed: 01/17/2023] Open
Abstract
Pioglitazone, a therapeutic drug for diabetes, possesses full PPAR-γ agonist activity and increase circulating adiponectin plasma concentration. Plasma adiponectin concentration decreases in hypertensive patients with renal dysfunctions. Present study investigated the reno-protective, altered excretory functions and renal haemodynamic responses to adrenergic agonists and ANG II following separate and combined therapy with pioglitazone in diabetic model of hypertensive rats. Pioglitazone was given orally [10mg/kg/day] for 28 days and adiponectin intraperitoneally [2.5μg/kg/day] for last 7 days. Groups of SHR received either pioglitazone or adiponectin in combination. A group of Wistar Kyoto rats [WKY] served as normotensive controls, whereas streptozotocin administered SHRs served as diabetic hypertensive rats. Metabolic data and plasma samples were taken on day 0, 8, 21 and 28. In acute studies, the renal vasoconstrictor actions of Angiotensin II [ANGII], noradrenaline [NA], phenylephrine [PE] and methoxamine [ME] were determined. Diabetic SHRs control had a higher basal mean arterial blood pressure than the WKY, lower RCBP and plasma adiponectin, higher creatinine clearance and urinary sodium excretion compared to WKY [all P<0.05] which were normalized by the individual drug treatments and to greater degree following combined treatment. Responses to intra-renal administration of NA, PE, ME and ANGII were larger in diabetic SHR than WKY and SHRs [P<0.05]. Adiponectin significantly blunted responses to NA, PE, ME and ANG II in diabetic treated SHRs by 40%, whereas the pioglitazone combined therapy with adiponectin further attenuated the responses to adrenergic agonists by 65%. [all P <0.05]. These findings suggest that adiponectin possesses renoprotective effects and improves renal haemodynamics through adiponectin receptors and PPAR-γ in diabetic SHRs, suggesting that synergism exists between adiponectin and pioglitazone. A cross-talk relationship also supposed to exists between adiponectin receptors, PPAR-γ and alpha adrenoceptors in renal vasculature of diabetic SHRs.
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Affiliation(s)
- Sheryar Afzal
- School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia
- Faculty of Pharmacy, MAHSA University, Selangor, Malaysia
- * E-mail:
| | - Munavvar Abdul Sattar
- School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia
- Faculty of Pharmacy, MAHSA University, Selangor, Malaysia
| | | | - Olorunfemi A. Eseyin
- School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia
- Department of Physiology, University College Cork, Cork, Ireland
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Fetal Growth Trajectories and Their Association with Maternal, Cord Blood, and 5-year Child Adipokines. J Nutr Metab 2020; 2020:4861523. [PMID: 33029393 PMCID: PMC7530496 DOI: 10.1155/2020/4861523] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 07/22/2020] [Accepted: 08/23/2020] [Indexed: 11/18/2022] Open
Abstract
Background The growth of the fetus is a complex process influenced by multiple factors. Studies have highlighted the important role of biochemical growth markers such as leptin and adiponectin on fetal growth. Objective To compare fetal growth trajectories with biochemical growth markers from maternal blood samples at 28 weeks' gestation, cord blood samples at birth, and in child blood samples at 5 years of age from mother-infant pairs who were part of the longitudinal ROLO study. Methods 781 mother-infant pairs from the ROLO and ROLO Kids study were included. Ultrasound measurements and birth weight were used to develop fetal growth trajectory groups for estimated abdominal circumference and estimated weight. Blood serum levels of leptin, adiponectin, insulin, TNF-alpha, and IL-6 from maternal, cord, and 5-year child samples were recorded. ANOVA and chi-square tests were applied to test the associations between fetal growth trajectory membership and maternal and child biochemical growth indicators. The influence of child sex was also investigated. Results Male sex was associated with a faster weight trajectory compared to females (p=0.001). At 28 weeks' gestation, maternal leptin levels were significantly higher in mothers with a fetus on a slower estimated abdominal circumference trajectory compared to fast (25616 [IQR: 11656.0 to 35341.0] vs. 14753.8 [IQR: 8565.4 to 24308.1], p < 0.001) and maternal adiponectin levels were lower in fetuses on a slower estimated abdominal circumference trajectory compared to a fast trajectory (22.4 [IQR: 13.6 to 35.9] vs. 27.6 [IQR: 17.6 to 46.3], p=0.027). No associations were noted with inflammatory markers. No associations were identified between fetal growth trajectories and growth markers at 5 years of age. Conclusions This study shows that male sex is associated with an accelerated estimated weight trajectory. Furthermore, high leptin and low adiponectin in maternal serum in late gestation are associated with a slower fetal growth trajectory. No associations were identified with blood growth markers after pregnancy.
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