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1
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Man AWC, Xia N, Li H. Vascular effects of perivascular adipose tissue-derived chemerin in obesity-associated cardiovascular disease. Cardiovasc Diabetol 2025; 24:249. [PMID: 40514684 PMCID: PMC12164128 DOI: 10.1186/s12933-025-02814-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 06/04/2025] [Indexed: 06/16/2025] Open
Abstract
Perivascular adipose tissue (PVAT) is a unique and metabolically active adipose tissue that is adjacent to most systemic blood vessels. Healthy PVAT exerts anticontractile and anti-inflammatory effects, contributing to vascular protection. However, during obesity, PVAT becomes proinflammatory and profibrotic, exacerbating vascular dysfunction. Chemerin, a multifunctional adipokine, has emerged as a key regulator of vascular tone, inflammation, and remodeling. Although liver-derived chemerin dominates the circulating chemerin pool, PVAT-derived chemerin plays a more localized and functionally important role in vascular pathophysiology because of its proximity to the vessel wall. This review highlights the role of PVAT-derived chemerin in vascular health, the mechanistic involvement of PVAT-derived chemerin in certain aspects of obesity-associated cardiovascular diseases, and the therapeutic potential of targeting PVAT-derived chemerin.
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Affiliation(s)
- Andy W C Man
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, 55131, Mainz, Germany
| | - Ning Xia
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, 55131, Mainz, Germany.
| | - Huige Li
- Department of Pharmacology, University Medical Center, Johannes Gutenberg University, 55131, Mainz, Germany.
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2
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Wen RM, Wang HX. Effect of adipokines on bone marrow mesenchymal stem cell function. World J Stem Cells 2025; 17:106150. [DOI: 10.4252/wjsc.v17.i5.106150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 03/23/2025] [Accepted: 04/09/2025] [Indexed: 05/26/2025] Open
Abstract
During excessive adipose tissue accumulation, various adipokines such as visfatin, chemerin, vaspin, and adiponectin are released into systemic circulation, thereby influencing metabolic tissue function throughout the body. As multifunctional signaling molecules secreted by adipose tissue, adipokines play a pivotal role in metabolic regulation, inflammatory response, and tissue homeostasis. Recent studies have demonstrated that adipokines can influence skeletal system repair and regeneration by modulating bone marrow-derived mesenchymal stem cell (BMSC) proliferation, differentiation, migration, and immunomodulatory functions. However, different adipokines have distinct roles in regulating BMSC function, but their underlying molecular mechanisms are not fully understood. In this review, we systematically summarize the specific mechanisms of action and potential clinical applications of visfatin, chemerin, vaspin, and adiponectin on BMSC function in order to reveal new mechanisms of interaction between adipokines and BMSCs. The aim is to provide a theoretical basis for targeted treatment strategies for bone diseases targeting adipokines.
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Affiliation(s)
- Rui-Ming Wen
- School of Sports Health, Shenyang Sport University, Shenyang 110102, Liaoning Province, China
| | - Hai-Xia Wang
- College of Exercise and Health, Shenyang Sport University, Shenyang 110102, Liaoning Province, China
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3
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Martins FF, Amarante MDSM, Oliveira DS, Vasques‐Monteiro IML, Souza‐Mello V, Daleprane JB, Camillo CDS. Obesity, White Adipose Tissue, and Adipokines Signaling in Male Reproduction. Mol Nutr Food Res 2025; 69:e70054. [PMID: 40195898 PMCID: PMC12087738 DOI: 10.1002/mnfr.70054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 02/19/2025] [Accepted: 03/17/2025] [Indexed: 04/09/2025]
Abstract
Currently, obesity is a global pandemic characterized by systemic metabolic complications that negatively impact several organs, including white adipose tissue (WAT) and the tissues of the male reproductive system. Since the discovery of leptin in 1994, WAT has been recognized as a dynamic endocrine organ for secreting a series of molecules with hormonal functions, collectively called adipokines. The link between obesity, WAT, adipokines, and the male reproductive system is direct and little explored. With changes in nutritional status, WAT undergoes morphofunctional changes, and the secretion of adipokines is altered, negatively impacting reproductive mechanisms, including steroidogenesis and spermatogenesis. In this review, we address in an updated way the structural and functional characteristics of WAT as well as the link between obesity and changes in the signaling pathways of the adipokines leptin, adiponectin, resistin, visfatin, apelin, chemerin, omentin-1, vaspin, and asprosin in male reproduction. Understanding the relationship between obesity, these adipokines, and reproductive dysfunction can contribute to new strategies for the treatment of subfertility and male infertility.
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Affiliation(s)
| | | | - Daiana Santana Oliveira
- Laboratory of MorphometryMetabolism and Cardiovascular DiseasesBiomedical CenterInstitute of BiologyRio de Janeiro State UniversityRio de JaneiroBrazil
| | - Isabela Macedo Lopes Vasques‐Monteiro
- Department of Basic and Experimental NutritionLaboratory for Studies of Interactions Between Nutrition and GeneticsLEINGRio de Janeiro State UniversityRio de JaneiroBrazil
| | - Vanessa Souza‐Mello
- Laboratory of MorphometryMetabolism and Cardiovascular DiseasesBiomedical CenterInstitute of BiologyRio de Janeiro State UniversityRio de JaneiroBrazil
| | - Julio Beltrame Daleprane
- Department of Basic and Experimental NutritionLaboratory for Studies of Interactions Between Nutrition and GeneticsLEINGRio de Janeiro State UniversityRio de JaneiroBrazil
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Yu X, Pan X, Huang M, Lin X, Wang X. Chemerin mediates exercise-induced improvements of bone microstructure and bone mass in diabetes or high fat diet mice. Mol Cell Endocrinol 2025; 599:112471. [PMID: 39864488 DOI: 10.1016/j.mce.2025.112471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 01/15/2025] [Accepted: 01/22/2025] [Indexed: 01/28/2025]
Abstract
To clarify the roles and mechanisms of adipokine chemerin in exercise-induced bone improvements in type 2 diabetes mellitus (DM) mice and mice fed on high fat diet (HFD). DM mice were established by HFD + streptozotocin injection, exogenous chemerin was supplemented prior to running, and found that exogenous chemerin reversed 6-week exercise-induced improvements in cancellous bone parameters in DM mice. While adipose-specific chemerin knockout improved microstructure and mass of cancellous bone in HFD mice and further increased exercise-induced bone improvements, accompanied with promoted osteogenesis and inhibited osteoclasis represented as the changes of RANKL, M-CSF, Runx2, Osterix, OPG, ALP and CTSK. These results indicated that reduced chemerin contributed to exercise-induced enhancements in the microstructure and mass of cancellous bone in DM and HFD mice in association with osteogenesis promotion and osteoclasis inhibition, which is beneficial to clarify chemerin's impact on bone remodeling in metabolic diseases at sedentary and exercise states.
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MESH Headings
- Animals
- Diet, High-Fat/adverse effects
- Physical Conditioning, Animal
- Chemokines/metabolism
- Chemokines/pharmacology
- Chemokines/genetics
- Male
- Diabetes Mellitus, Experimental/pathology
- Diabetes Mellitus, Experimental/metabolism
- Diabetes Mellitus, Experimental/physiopathology
- Intercellular Signaling Peptides and Proteins/metabolism
- Osteogenesis/drug effects
- Mice, Inbred C57BL
- Bone and Bones/pathology
- Bone and Bones/metabolism
- Mice
- Diabetes Mellitus, Type 2/metabolism
- Diabetes Mellitus, Type 2/pathology
- Diabetes Mellitus, Type 2/physiopathology
- Mice, Knockout
- Cancellous Bone/pathology
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Affiliation(s)
- Xiaohan Yu
- Shanghai University of Sport, School of Exercise and Health, Shanghai, 200438, China
| | - Xinyan Pan
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Mei Huang
- Shanghai University of Sport, School of Exercise and Health, Shanghai, 200438, China
| | - Xiaoye Lin
- Shanghai University of Sport, School of Exercise and Health, Shanghai, 200438, China
| | - Xiaohui Wang
- Shanghai University of Sport, School of Exercise and Health, Shanghai, 200438, China.
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5
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Qu J, Fu S, Yin L, Zhang Q, Wang X. Chemerin influences blood lipid of aged male mice under high fat diet and exercise states through regulating the distribution and browning of white adipose tissue. Cytokine 2024; 181:156689. [PMID: 38981157 DOI: 10.1016/j.cyto.2024.156689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 05/13/2024] [Accepted: 07/02/2024] [Indexed: 07/11/2024]
Abstract
BACKGROUND With aging, white adipose tissue (WAT) undergoes distribution change and browning inhibition, which could be attenuated by exercise. Adipokine chemerin exerts roles in the above changes of WAT, and our previous studies demonstrated the effect of decreased chemerin on exercise-induced improvement of glucose and lipid metabolism in high fat diet (HFD) feeding male mice, so this study is to clarify whether chemerin's effects on glucose and lipid metabolism are associated with the distribution and browning of WAT. METHODS After diet and exercise interventions, body weight and adipose tissue contents in different depots of male mice were weighed, body composition and energy metabolism parameters were determined by Echo MRI Body Composition Analyzer and metabolic cage, respectively. The levels of serum adiponectin and leptin were detected by ELISA, and the protein levels of PGC-1α, UCP1, adiponectin and leptin in WAT were measured by Western blot. RESULTS Chemerin knockout exacerbated HFD-induced weight gain, upregulated the increases of visceral and subcutaneous WAT (vWAT and sWAT, especial in sWAT), and inhibited WAT browning, but improved blood lipid. Exercise reduced the body weight and WAT distribution, increased sWAT browning and further improved blood lipid in aged HFD male mice, which were abrogated by chemerin knockout. Detrimental alterations of leptin, adiponectin and adiponectin/leptin ratio were discovered in the serum and WAT of aged HFD chemerin(-/-) mice; and exercise-induced beneficial changes in these adipokines were blocked by chemerin knockout. CONCLUSION Chemerin influences blood lipid of aged male mice under HFD and exercise states through regulating the distribution and browning of WAT, which might be related to the changes of adiponectin, leptin and adiponectin/leptin ratio.
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Affiliation(s)
- Jing Qu
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China; School of Physical Education, Minzu Normal University of Xingyi, Xingyi, Guizhou, China
| | - Shaoting Fu
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China; Department of Kinesiology, College of Physical Education, Shanghai Normal University, Shanghai, China
| | - Lijun Yin
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Qilong Zhang
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China
| | - Xiaohui Wang
- School of Exercise and Health, Shanghai University of Sport, Shanghai, China.
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6
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Tariq S, Jabbar S, Ahmad A, Tariq S. Bridging the Gap: A narrative review of osteoporosis disability, adipokines, and the role of AI in postmenopausal women. Pak J Med Sci 2024; 40:1572-1577. [PMID: 39092029 PMCID: PMC11255809 DOI: 10.12669/pjms.40.7.9072] [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: 11/06/2023] [Revised: 03/06/2024] [Accepted: 03/29/2024] [Indexed: 08/04/2024] Open
Abstract
Osteoporosis is a global health concern characterized by reduced bone density and compromised bone quality, resulting in an increased risk of fractures, particularly in postmenopausal women. The assessment of bone mineral density (BMD) plays a pivotal role in diagnosing osteoporosis, as it accounts for approximately 70% of overall bone strength. The World Health Organization (WHO) has endorsed BMD measurement as a reliable method for diagnosing this condition. In Pakistan, the incidence of bone fractures is on the rise, largely attributable to an aging population and a range of contributing factors. Understanding the global and local prevalence of osteoporosis, its impact on morbidity and mortality, and the contributing factors is vital for developing effective preventive and therapeutic strategies. The role of adipokines, including chemerin, vaspin, and omentin-1, in bone metabolism is an emerging area of investigation. These adipokines play diverse roles in physiology, ranging from inflammation and metabolic regulation to cardiovascular health. Understanding their potential impact on bone health is a topic of ongoing research. The intricate relationship between bone density, bone quality, and overall bone strength is central to understanding the diagnosis and management of osteoporosis. Current innovation in machine learning and predictive model can bring revolution in the field of bone health and osteoporosis. Early identification of people with osteoporosis or risk of fracture through machine learning can prevent disability and improve the quality of life.
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Affiliation(s)
- Saba Tariq
- Saba Tariq, Department of Pharmacology & Therapeutics, University Medical and Dental College, The University of Faisalabad, Post-doctoral Fellow, University of Birmingham, England, UK
| | - Sohail Jabbar
- Sohail Jabbar, Department of Computer Science, College of Computer and Information Sciences, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
| | - Awais Ahmad
- Awais Ahmad, Information Systems Department, College of Computer and Information Sciences, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
| | - Sundus Tariq
- Sundus Tariq, Department of Physiology, International School of Medicine, Istanbul Medipol University, Research Institute for Health, Sciences and Technologies (SABITA), Turkey
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Jerang M, Kumar R, Gurusubramanian G, Roy VK. Comparative expression and localization of visfatin, chemerin, and chemerin receptor proteins in a heat-stressed mouse testis. Tissue Cell 2024; 88:102374. [PMID: 38598873 DOI: 10.1016/j.tice.2024.102374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 04/04/2024] [Accepted: 04/04/2024] [Indexed: 04/12/2024]
Abstract
The adipokines, visfatin, chemerin, and its receptor are expressed in the testis. It has also been shown that heat-stress alters the secretion and expression of other adipokines. Testicular heat-stress is now well known to cause the impairment in the testis. It has also been documented that heat-stress changes the expression of genes and proteins in the testis. To the best of our knowledge, the expression and localization of visfatin chemerin and its receptor have not been investigated in the heat-stressed testis. Therefore, the present study has investigated the expression and localization of these proteins in the heat-stressed testis. The expression of visfatin and chemerin and receptor exhibits a differential repossess against the heat stress. Visfatin expression was up-regulated while chemerin and chemerin receptor was down-regulated in the heat-stressed testis as shown by western blot analysis. The immunolocalization of visfatin and chemerin showed increased abundance in the seminiferous tubules of heat-stressed mice testis. Furthermore, abundance of visfatin, chemerin, and its receptor showed a decrease in abundance in the Leydig cells of heat-stressed testis. The decreased abundance of these proteins in the Leydig cells coincides with decreased 3β-HSD immunostaining along with decreased testosterone levels. These results suggest that heat-stress might decrease testosterone secretion by modulating visfatin and chemerin in the Leydig cells. The increased abundance of visfatin and chemerin in the primary spermatocytes, round spermatid, and multinucleated germ cells also coincides with increased immunostaining of active caspase-3. Moreover, expression of Bcl-2 was down-regulated, and expression of active caspase-3 and HSP70 were up-regulated along with increased oxidative stress in the heat-stressed testis, suggesting stimulated apoptosis. In conclusion, our results showed that visfatin, chemerin, and its receptor are differentially expressed in the testis under heat-stress and within the testis also it might differentially regulate testosterone biosynthesis in the Leydig cells and apoptosis in the seminiferous tubules.
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Affiliation(s)
- Miti Jerang
- Department of Zoology, Mizoram University, Aizawl, Mizoram 796004, India
| | - Rahul Kumar
- Department of Biotechnology, Mahatma Gandhi Central University, Motihari, Bihar 845401, India
| | | | - Vikas Kumar Roy
- Department of Zoology, Mizoram University, Aizawl, Mizoram 796004, India.
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Ma Y, Li J, Mai J, Guo H, Ding L, Li J, Xiao J, Li M, Fang W, Zhang S, Xu L, Wang H. Ginsenoside Rb2 exhibits therapeutic value for male osteoporosis in orchiectomy mice by suppressing osteoclastogenesis and modulating NF-κB/MAPK signaling pathways. Food Funct 2024; 15:1583-1597. [PMID: 38240189 DOI: 10.1039/d3fo04334g] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2024]
Abstract
Osteoporosis (OP) is a systemic disorder characterized by decreased bone mass as well as deteriorated microarchitecture. Although OP in men is common, it has received much less attention than that in women. Ginseng, a famous traditional herb in Asia, is used to strengthen and repair bones by invigorating vital bioenergy and maintaining body homeostasis in dietary intake and clinical applications. However, there is currently no study investigating the impact of ginseng and its active compounds on male osteoporosis. In this study, RNA sequencing and bioinformatic analysis were conducted to reveal the influence of Ginsenoside-Rb2 on RAW264.7 cells and its underlying signaling pathways. The potential anti-osteoporosis effects of Rb2 as well as its molecular mechanisms were elucidated in RAW264.7 cells and BMMs by TRAP staining, F-actin belt staining, qRT-PCR and WB. Moreover, orchiectomy (ORX) was utilized to demonstrate the influence of Rb2 on bone mass loss in vivo by micro-CT scanning, and H&E, TRAP, and IHC staining. The results suggested that Rb2 suppressed osteoclastogenesis and mitigated bone loss in orchiectomy mice through NF-κB/MAPK signaling pathways. These findings indicate that ginseng as well as its active component Rb2 have potential therapeutic value in the management of osteoporosis in men.
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Affiliation(s)
- Yanhuai Ma
- First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jianliang Li
- First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangzhou First People's Hospital, Second Affiliated Hospital of South China University of Technology, Guangzhou, China
| | - Jiale Mai
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- Foshan Hospital of Chinese Medicine, Eighth Clinical School, Guangzhou University of Chinese Medicine, Foshan, China
| | - Huizhi Guo
- Department of Spine Surgery, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lingli Ding
- First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jinglan Li
- Department of Spine Surgery, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiacong Xiao
- First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Miao Li
- First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Weihua Fang
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shuncong Zhang
- Department of Spine Surgery, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Liangliang Xu
- First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Orthopaedic Surgery, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, 16 Jichang Road, Baiyun District, Guangzhou, 510405, China
| | - Haibin Wang
- First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
- The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Orthopaedic Surgery, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, 16 Jichang Road, Baiyun District, Guangzhou, 510405, China
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Hu K, Deya Edelen E, Zhuo W, Khan A, Orbegoso J, Greenfield L, Rahi B, Griffin M, Ilich JZ, Kelly OJ. Understanding the Consequences of Fatty Bone and Fatty Muscle: How the Osteosarcopenic Adiposity Phenotype Uncovers the Deterioration of Body Composition. Metabolites 2023; 13:1056. [PMID: 37887382 PMCID: PMC10608812 DOI: 10.3390/metabo13101056] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/26/2023] [Accepted: 10/04/2023] [Indexed: 10/28/2023] Open
Abstract
Adiposity is central to aging and several chronic diseases. Adiposity encompasses not just the excess adipose tissue but also body fat redistribution, fat infiltration, hypertrophy of adipocytes, and the shifting of mesenchymal stem cell commitment to adipogenesis. Bone marrow adipose tissue expansion, inflammatory adipokines, and adipocyte-derived extracellular vesicles are central to the development of osteopenic adiposity. Adipose tissue infiltration and local adipogenesis within the muscle are critical in developing sarcopenic adiposity and subsequent poorer functional outcomes. Ultimately, osteosarcopenic adiposity syndrome is the result of all the processes noted above: fat infiltration and adipocyte expansion and redistribution within the bone, muscle, and adipose tissues, resulting in bone loss, muscle mass/strength loss, deteriorated adipose tissue, and subsequent functional decline. Increased fat tissue, typically referred to as obesity and expressed by body mass index (the latter often used inadequately), is now occurring in younger age groups, suggesting people will live longer with the negative effects of adiposity. This review discusses the role of adiposity in the deterioration of bone and muscle, as well as adipose tissue itself. It reveals how considering and including adiposity in the definition and diagnosis of osteopenic adiposity, sarcopenic adiposity, and osteosarcopenic adiposity will help in better understanding the pathophysiology of each and accelerate possible therapies and prevention approaches for both relatively healthy individuals or those with chronic disease.
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Affiliation(s)
- Kelsey Hu
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Elizabeth Deya Edelen
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Wenqing Zhuo
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Aliya Khan
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Josselyne Orbegoso
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Lindsey Greenfield
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Berna Rahi
- Department of Human Sciences, Sam Houston State University College of Health Sciences, Huntsville, TX 77341, USA;
| | - Michael Griffin
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
| | - Jasminka Z. Ilich
- Institute for Successful Longevity, Florida State University, Tallahassee, FL 32304, USA;
| | - Owen J. Kelly
- Department of Molecular and Cellular Biology, Sam Houston State University College of Osteopathic Medicine, Conroe, TX 77304, USA; (K.H.); (E.D.E.); (W.Z.); (A.K.); (J.O.); (L.G.); (M.G.)
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10
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Liu M, Lan Q, Yang L, Deng Q, Wei T, Zhao H, Peng P, Lin X, Chen Y, Ma H, Wei H, Yin Y. Genome-Wide Association Analysis Identifies Genomic Regions and Candidate Genes for Growth and Fatness Traits in Diannan Small-Ear (DSE) Pigs. Animals (Basel) 2023; 13:ani13091571. [PMID: 37174608 PMCID: PMC10177038 DOI: 10.3390/ani13091571] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 04/13/2023] [Accepted: 05/04/2023] [Indexed: 05/15/2023] Open
Abstract
In the livestock industry, the growth and fatness traits are directly related to production efficiency and economic profits. As for Diannan small-ear (DSE) pigs, a unique indigenous breed, the genetic architecture of growth and fatness traits is still elusive. The aim of this study was to search the genetic loci and candidate genes associated with phenotypic traits in DSE pigs using GWAS based on the Geneseek Porcine 50K SNP Chip data. A total of 22,146 single nucleotide polymorphisms (SNPs) were detected in 265 DSE pigs and used for Genome-wide association studies (GWAS) analysis. Seven SNPs were found to be associated with back height, chest circumference, cannon bone circumference, and backfat thickness at the suggestive significance level. Based on gene annotation results, these seven SNPs were, respectively, mapped to the following candidate genes, VIPR2, SLC10A2, NUCKS1, MCT1, CHCHD3, SMOX, and GPR1, which are mainly involved with adipocyte differentiation, lipid metabolism, skeletal muscle development, and average daily weight gain. Our work offers novel insights into the genetic architecture of economically important traits in swine and may play an important role in breeding using molecular markers in the DSE breed.
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Affiliation(s)
- Mei Liu
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Qun Lan
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Long Yang
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Qiuchun Deng
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Taiyun Wei
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming 650201, China
| | - Heng Zhao
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming 650201, China
| | - Peiya Peng
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Xiaoding Lin
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Yuhan Chen
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Haiming Ma
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
| | - Hongjiang Wei
- Yunnan Province Key Laboratory for Porcine Gene Editing and Xenotransplantation, Yunnan Agricultural University, Kunming 650201, China
| | - Yulong Yin
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China
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Deepika F, Bathina S, Armamento-Villareal R. Novel Adipokines and Their Role in Bone Metabolism: A Narrative Review. Biomedicines 2023; 11:644. [PMID: 36831180 PMCID: PMC9953715 DOI: 10.3390/biomedicines11020644] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 02/02/2023] [Accepted: 02/14/2023] [Indexed: 02/23/2023] Open
Abstract
The growing burden of obesity and osteoporosis is a major public health concern. Emerging evidence of the role of adipokines on bone metabolism has led to the discovery of novel adipokines over the last decade. Obesity is recognized as a state of adipose tissue inflammation that adversely affects bone health. Adipokines secreted from white adipose tissue (WAT) and bone marrow adipose tissue (BMAT) exerts endocrine and paracrine effects on the survival and function of osteoblasts and osteoclasts. An increase in marrow fat is implicated in osteoporosis and, hence, it is crucial to understand the complex interplay between adipocytes and bone. The objective of this review is to summarize recent advances in our understanding of the role of different adipokines on bone metabolism. METHODS This is a comprehensive review of the literature available in PubMED and Cochrane databases, with an emphasis on the last five years using the keywords. RESULTS Leptin has shown some positive effects on bone metabolism; in contrast, both adiponectin and chemerin have consistently shown a negative association with BMD. No significant association was found between resistin and BMD. Novel adipokines such as visfatin, LCN-2, Nesfatin-1, RBP-4, apelin, and vaspin have shown bone-protective and osteoanabolic properties that could be translated into therapeutic targets. CONCLUSION New evidence suggests the potential role of novel adipokines as biomarkers to predict osteoporosis risk, and as therapeutic targets for the treatment of osteoporosis.
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Affiliation(s)
- Fnu Deepika
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX 77030, USA
| | - Siresha Bathina
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX 77030, USA
| | - Reina Armamento-Villareal
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
- Center for Translational Research on Inflammatory Disease, Michael E DeBakey Veterans Affairs (VA) Medical Center, Houston, TX 77030, USA
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12
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Wang C, Zhang M, Yan J, Wang R, Wang Z, Sun X, Dong S. Chemokine-like receptor 1 deficiency impedes macrophage phenotypic transformation and cardiac repair after myocardial infarction. Int J Cardiol 2023; 372:6-14. [PMID: 36513282 DOI: 10.1016/j.ijcard.2022.12.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 12/02/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Timely and appropriate transformation of macrophage phenotypes from proinflammatory to anti-inflammatory is essential for cardiac repair after myocardial infarction (MI). Chemokine-like receptor 1 (CMKLR1), which is expressed on macrophages, is regulated by proinflammatory and anti-inflammatory stimuli. However, the contribution of CMKLR1 to macrophage phenotypic transformation and the role it plays in modulating cardiac repair after MI remain unclear. METHODS CMKLR1 knockout (CMKLR1-/-) mice were generated by CRISPR/Cas-mediated genome engineering. A model of murine MI was induced by permanent ligation along the left anterior descending artery. Cardiac function was evaluated by echocardiography. Infarct size and collagen deposition were detected by Masson's trichrome staining. Cardiac macrophages were obtained by fluorescence-activated cell sorting. The protein and mRNA expression of associated molecules was determined by Western blotting and qRT-PCR. RESULTS We demonstrated that macrophages highly expressed CMKLR1 and accumulated in murine infarcted hearts during the anti-inflammatory reparative phase of MI. CMKLR1 deficiency impaired cardiac function, increased infarct size, induced maladaptive cardiac remodeling, and decreased long-term survival after MI. Furthermore, CMKLR1 deficiency impeded macrophage phenotypic transformation from M1 to M2 in vivo and in vitro. In addition, we demonstrated that CMKLR1 signaling through the PI3K/Akt/mTOR pathway stimulated C/EBPβ activation while simultaneously limiting NF-κB activation, thereby promoting anti-inflammatory and prohibiting proinflammatory macrophage polarization. CONCLUSIONS Our results reveal that CMKLR1 deficiency impedes macrophage phenotypic transformation and cardiac repair after MI involving the PI3K/AKT/mTOR pathway. CMKLR1 may thus represent a potential therapeutic target for MI.
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Affiliation(s)
- Caiping Wang
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China
| | - Min Zhang
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China
| | - Jianlong Yan
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China
| | - Rongning Wang
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China
| | - Zhefeng Wang
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China
| | - Xin Sun
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.
| | - Shaohong Dong
- Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.
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Yu M, Yang Y, Huang C, Ge L, Xue L, Xiao Z, Xiao T, Zhao H, Ren P, Zhang JV. Chemerin: A Functional Adipokine in Reproductive Health and Diseases. Biomedicines 2022; 10:biomedicines10081910. [PMID: 36009457 PMCID: PMC9406010 DOI: 10.3390/biomedicines10081910] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 07/09/2022] [Accepted: 07/11/2022] [Indexed: 11/30/2022] Open
Abstract
As a multifaceted adipokine, chemerin has been found to perform functions vital for immunity, adiposity, and metabolism through its three known receptors (chemokine-like receptor 1, CMKLR1; G-protein-coupled receptor 1, GPR1; C-C motif chemokine receptor-like 2, CCRL2). Chemerin and the cognate receptors are also expressed in the hypothalamus, pituitary gland, testis, ovary, and placenta. Accumulating studies suggest that chemerin participates in normal reproduction and underlies the pathological mechanisms of certain reproductive system diseases, including polycystic ovary syndrome (PCOS), preeclampsia, and breast cancer. Herein, we present a comprehensive review of the roles of the chemerin system in multiple reproductive processes and human reproductive diseases, with a brief discussion and perspectives on future clinical applications.
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Affiliation(s)
- Ming Yu
- Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Key Laboratory of Metabolic Health, Shenzhen 518055, China
| | - Yali Yang
- Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Key Laboratory of Metabolic Health, Shenzhen 518055, China
- Shenzhen College of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen 518055, China
| | - Chen Huang
- Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Key Laboratory of Metabolic Health, Shenzhen 518055, China
| | - Lei Ge
- Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Key Laboratory of Metabolic Health, Shenzhen 518055, China
- Shenzhen College of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen 518055, China
| | - Li Xue
- Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Key Laboratory of Metabolic Health, Shenzhen 518055, China
- Shenzhen College of Advanced Technology, University of Chinese Academy of Sciences, Shenzhen 518055, China
| | - Zhonglin Xiao
- Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Key Laboratory of Metabolic Health, Shenzhen 518055, China
| | - Tianxia Xiao
- Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Key Laboratory of Metabolic Health, Shenzhen 518055, China
| | - Huashan Zhao
- Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Key Laboratory of Metabolic Health, Shenzhen 518055, China
| | - Peigen Ren
- Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Key Laboratory of Metabolic Health, Shenzhen 518055, China
| | - Jian V. Zhang
- Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Shenzhen Key Laboratory of Metabolic Health, Shenzhen 518055, China
- Correspondence:
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Tariq S, Tariq S, Abualhamael SA, Shahzad M. Effect of Ibandronate Therapy on Serum Chemerin, Vaspin, Omentin-1 and Osteoprotegerin (OPG) in Postmenopausal Osteoporotic Females. Front Pharmacol 2022; 13:822671. [PMID: 35222038 PMCID: PMC8864312 DOI: 10.3389/fphar.2022.822671] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 01/14/2022] [Indexed: 11/13/2022] Open
Abstract
Osteoporosis is a condition in which bone mineral density is reduced due to altered bone microstructure, which results in increased skeletal fragility and incidence of various types of fractures. Adipokines such as chemerin, vaspin, omentin-1 and osteoprotegerin are involved in bone remodeling. The current study was designed to determine the changes in circulating chemerin, vaspin, omentin-1, and osteoprotegerin levels after treatment with oral ibandronate 150 mg in postmenopausal osteoporotic females. The present study enrolled 107 postmenopausal osteoporotic females from a tertiary care hospital in Faisalabad, Pakistan, based on stringent inclusion and exclusion criteria. Sixty-six healthy postmenopausal, non-osteoporotic females with no systemic illness were chosen from the general population. The assessment of bone mineral density (BMD) was done using a DEXA scan. Serum levels of chemerin, vaspin, omentin-1 and osteoprotegerin were estimated using commercially available enzyme-linked immunosorbent assay kits. The collected data were analyzed with the Statistical Package for Social Sciences (SPSS) version 24. Following 6 months of ibandronate treatment, there was a significant decrease of 24.24% (p < .033) in serum chemerin levels, as well as a significant increase in serum vaspin levels 343.32% (p < .001) and osteoprotegerin levels 19.57% (p < .001), with no significant change in omentin-1 levels. Thus, an increase in serum chemerin levels and a decrease in serum vaspin and osteoprotegerin levels could be implicated in osteoporosis.
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Affiliation(s)
- Saba Tariq
- Department of Pharmacology and Therapeutics, University Medical and Dental College, The University of Faisalabad, Faisalabad, Pakistan
- Department of Pharmacology, University of Health Sciences, Lahore, Pakistan
| | - Sundus Tariq
- Department of Physiology and Cell Biology, University Medical and Dental College, The University of Faisalabad, Faisalabad, Pakistan
- Department of Physiology, University of Health Sciences, Lahore, Pakistan
| | | | - Muhammad Shahzad
- Department of Pharmacology, University of Health Sciences, Lahore, Pakistan
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Han L, Zhang Y, Wan S, Wei Q, Shang W, Huang G, Fang P, Min W. Loss of chemerin triggers bone remodeling in vivo and in vitro. Mol Metab 2021; 53:101322. [PMID: 34416393 PMCID: PMC8450264 DOI: 10.1016/j.molmet.2021.101322] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 08/11/2021] [Accepted: 08/12/2021] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE It was reported that chemerin as an adipocyte-secreted protein could regulate bone resorption and bone formation. However, the specific molecular and gene mechanism of the chemerin role is unclear. The aim of this study is to evaluate the role of chemerin in bone metabolism. METHODS In the present study, we investigated the effects of chemerin on bone remodeling in rarres2 knockout (Rarres2-/-) mice and examined the role of chemerin as a determinant of osteoblast and osteoclast differentiation in Mc3t3-E1 and Raw264.7 cell lines. RESULTS The results showed that the bone mineral density and volume score, trabecular thickness, weight and bone formation marker BALP increased, but Tb.Sp and bone resorption marker TRACP-5b decreased in Rarres2-/- mice. Furthermore, the mRNA and protein expression of biomarkers of osteoblasts (β-catenin, RANKL and OPG) significantly increased, but those of osteoclasts (CTSK and RANK) decreased in Rarres2-/- mice. In vitro, chemerin markedly suppressed β-catenin and OPG, but increased RANKL, CTSK and RANK expression. Moreover, knockdown of chemerin using RNA interference enhanced osteoblastogenesis genes and inhibited osteoclastogenesis genes in Mc3t3-E1 and Raw264.7 cells. CONCLUSIONS Taken together, these data suggest an inhibitive effect of chemerin on osteoblast differentiation and proliferation through inhibition of Wnt/β-catenin signaling, as well as a stimulative effect of chemerin on osteoclast differentiation and proliferation via activation of RANK signaling. The maintenance of a low chemerin level may be a strategy for the prevention and treatment of osteoporosis.
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Affiliation(s)
- Long Han
- Department of Bone injury of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yu Zhang
- Department of Bone injury of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China
| | - Shiwei Wan
- Department of Bone injury of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Qingbo Wei
- Key Laboratory of Acupuncture and Medicine Research of Minister of Education, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Wenbing Shang
- Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Guichen Huang
- Department of Bone injury of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
| | - Penghua Fang
- Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Wen Min
- Department of Bone injury of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China; Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
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16
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Li J, Zhang T, Huang C, Xu M, Xie W, Pei Q, Xie X, Wang B, Li X. Chemerin located in bone marrow promotes osteogenic differentiation and bone formation via Akt/Gsk3β/β-catenin axis in mice. J Cell Physiol 2021; 236:6042-6054. [PMID: 33492671 DOI: 10.1002/jcp.30290] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 01/06/2021] [Accepted: 01/09/2021] [Indexed: 12/11/2022]
Abstract
Chemerin, a secreted protein mainly produced by adipocytes and hepatocytes, plays a variety of roles in endocrine or paracrine signaling. As reported in human epidemiology, chemerin was correlated with osteoporosis. And the previous in vitro study found that chemerin knockdown promoted osteogenesis and inhibited adipogenesis. However, the function of chemerin in bone metabolism and the underlying mechanism remains unclear. In this study, we uncovered the in vivo function of chemerin in bone homeostasis. We discovered that in obese mice, chemerin was increased in serum, while decreased in the bone marrow; and the chemerin expression in bone tissue was positively correlated with osteogenic genes. To further investigate the function of chemerin in bone metabolism, we generated chemerin deficiency and overexpression mice. We found bone mass and osteogenesis were decreased in chemerin deficiency mice, while were increased in chemerin overexpression mice. Furthermore, we observed that the chemerin expression increased during osteogenic differentiation of MSCs. Besides, we verified that chemerin promoted osteogenic differentiation in C3H10T1/2 cells and BMSCs through Akt/Gsk3β/β-catenin axis. Treatment with Akt inhibitor (MK2206) abolished the promoting effect of chemerin on osteogenic differentiation and active β-catenin. Together, our results suggest chemerin in bone marrow, not in serum, promotes osteogenic differentiation and bone formation via Akt/Gsk3β/β-catenin axis. Chemerin may serve as a therapeutic strategy for osteoporosis.
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Affiliation(s)
- Jun Li
- Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China
| | - Ting Zhang
- Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China
| | - Chenglong Huang
- Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China
| | - Min Xu
- Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China
| | - Wenhua Xie
- Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China
| | - Qilin Pei
- Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China
| | - Xinxin Xie
- Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China
| | - Bin Wang
- Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China
| | - Xi Li
- Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China
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Guo X, Wu Z. GABARAP ameliorates IL-1β-induced inflammatory responses and osteogenic differentiation in bone marrow-derived stromal cells by activating autophagy. Sci Rep 2021; 11:11561. [PMID: 34078931 PMCID: PMC8172545 DOI: 10.1038/s41598-021-90586-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 05/13/2021] [Indexed: 12/13/2022] Open
Abstract
Bone mesenchymal stem cells (BMSCs) are the most commonly investigated progenitor cells in bone defect repair and osteoarthritis subchondral bone regeneration; however, these studies are limited by complex inflammatory conditions. In this study, we investigated whether pro-autophagic γ-aminobutyric acid receptor-associated protein (GABARAP) promotes BMSCs proliferation and osteogenic differentiation by modulating autophagy in the presence or absence of interleukin-1 beta (IL-1β) in vitro. The expression levels of all relevant factors were evaluated by qRT-PCR or western blotting where appropriate. BMSCs differentiation were assessed by Alizarin Red, alkaline phosphatase, safranin O, and Oil Red O staining. Furthermore, the interactions between autophagy and osteogenic differentiation were investigated by co-treatment with the autophagy inhibitor 3-methyladenine (3-MA). As the results, we found that treatment with recombinant human His6-GABARAP protein promoted cell proliferation, inhibited apoptosis, and reduced ROS generation by increasing autophagic activity, particularly when co-cultured with IL-1β. Moreover, His6-GABARAP could effectively increase the osteogenic differentiation of BMSCs. The expression levels of inflammatory factors were significantly decreased by His6-GABARAP treatment, whereas its protective effects were attenuated by 3-MA. This study demonstrates that GABARAP maintains BMSCs survival and strengthens their osteogenic differentiation in an inflammatory environment by upregulating mediators of the autophagy pathway.
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Affiliation(s)
- Xiaobo Guo
- Department of Orthopedics, Jincheng General Hospital, Jincheng, 048000, China.
| | - Zhenyuan Wu
- Department of Orthopedics, Jincheng General Hospital, Jincheng, 048000, China
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Estienne A, Ramé C, Ganier P, Chahnamian M, Barbe A, Grandhaye J, Dubois JP, Batailler M, Migaud M, Lecompte F, Adriaensen H, Froment P, Dupont J. Chemerin impairs food intake and body weight in chicken: Focus on hypothalamic neuropeptides gene expression and AMPK signaling pathway. Gen Comp Endocrinol 2021; 304:113721. [PMID: 33493505 DOI: 10.1016/j.ygcen.2021.113721] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/31/2020] [Accepted: 01/15/2021] [Indexed: 12/11/2022]
Abstract
Unlike mammals, the role of adipokines and more particularly of chemerin in the regulation of food intake is totally unknown in avian species. Here we investigated the effect of chemerin on the food and water consumption and on the body weight in chicken. We studied the effects on the plasma glucose and insulin concentrations and the hypothalamic neuropeptides and AMPK signaling pathway. Female broiler chickens were intraperitoneally injected, daily for 13 days with either vehicle (saline; n = 25) or chemerin (8 μg/kg; n = 25 and 16 μg/kg; n = 25). Food and water intakes were recorded 24 h after each administration. Overnight fasted animals were sacrificed at day 13 (D13), 24 h after the last injection and hypothalamus and left cerebral hemispheres were collected. Chemerin and its receptors protein levels were determined by western-blot. Gene expression of neuropeptide Y (Npy), agouti-related peptide (Agrp), corticotrophin releasing hormone (Crh), pro-opiomelanocortin (Pomc), cocaine and amphetamine-regulated transcript (Cart) and Taste 1 Receptor Member 1 (Tas1r1) were evaluated by RT-qPCR. In chicken, we found that the protein amount of chemerin, CCRL2 and GPR1 was similar in left cerebral hemisphere and hypothalamus whereas CMKLR1 was higher in hypothalamus. Chemerin administration (8 and 16 μg/kg) decreased both food intake and body weight compared to vehicle without affecting water intake and the size or volume of different brain subdivisions as determined by magnetic resonance imaging. It also increased plasma insulin levels whereas glucose levels were decreased. These data were associated with an increase in Npy and Agrp expressions and a decrease in Crh, Tas1r1 mRNA expression within the hypothalamus. Furthermore, chemerin decreased hypothalamic CMKLR1 protein expression and AMPK activation. Taken together, these results support that chemerin could be a peripheral appetite-regulating signal through modulation of hypothalamic peptides expression in chicken.
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Affiliation(s)
- Anthony Estienne
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France
| | - Christelle Ramé
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France
| | - Patrice Ganier
- INRAE - Unité Expérimentale du Pôle d'Expérimentation Avicole de Tours UEPEAT, 1295, Nouzilly, France
| | - Marine Chahnamian
- INRAE - Unité Expérimentale du Pôle d'Expérimentation Avicole de Tours UEPEAT, 1295, Nouzilly, France
| | - Alix Barbe
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France
| | - Jérémy Grandhaye
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France
| | - Jean-Philippe Dubois
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France
| | - Martine Batailler
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France
| | - Martine Migaud
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France
| | - François Lecompte
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France
| | - Hans Adriaensen
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France
| | - Pascal Froment
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France
| | - Joëlle Dupont
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France Université François Rabelais de Tours F-37041 Tours, France IFCE F-37380 Nouzilly, France.
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Estienne A, Bongrani A, Froment P, Dupont J. Apelin and chemerin receptors are G protein-coupled receptors involved in metabolic as well as reproductive functions: Potential therapeutic implications? ACTA ACUST UNITED AC 2021. [DOI: 10.1016/j.coemr.2020.09.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Feng X, Xia K, Ke Q, Deng R, Zhuang J, Wan Z, Luo P, Wang F, Zang Z, Sun X, Xiang AP, Tu X, Gao Y, Deng C. Transplantation of encapsulated human Leydig-like cells: A novel option for the treatment of testosterone deficiency. Mol Cell Endocrinol 2021; 519:111039. [PMID: 32980418 DOI: 10.1016/j.mce.2020.111039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/22/2020] [Accepted: 09/22/2020] [Indexed: 12/15/2022]
Abstract
Previous studies have demonstrated that the transplantation of alginate-poly-ʟ-lysine-alginate (APA)-encapsulated rat Leydig cells (LCs) provides a promising approach for treating testosterone deficiency (TD). Nevertheless, LCs have a limited capacity to proliferate, limiting the efficacy of LC transplantation therapy. Here, we established an efficient differentiation system to obtain functional Leydig-like cells (LLCs) from human stem Leydig cells (hSLCs). Then we injected APA-encapsulated LLCs into the abdominal cavities of castrated mice without an immunosuppressor. The APA-encapsulated cells survived and partially restored testosterone production for 90 days in vivo. More importantly, the transplantation of encapsulated LLCs ameliorated the symptoms of TD, such as fat accumulation, muscle atrophy and adipocyte accumulation in bone marrow. Overall, these results suggest that the transplantation of encapsulated LLCs is a promising new method for testosterone supplementation with potential clinical applications in TD.
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Affiliation(s)
- Xin Feng
- Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Kai Xia
- Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Qiong Ke
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Rongda Deng
- Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; KingMed Center for Clinical Laboratory CO., LTD, Guangzhou, China
| | - Jintao Zhuang
- Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zi Wan
- Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Peng Luo
- Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Fulin Wang
- Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhijun Zang
- Department of Infertility and Sexual Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiangzhou Sun
- Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Andy Peng Xiang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China; Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Xiang'an Tu
- Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Yong Gao
- Reproductive Medicine Center, The Key Laboratory for Reproductive Medicine of Guangdong Province, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Chunhua Deng
- Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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Chemerin Impairs In Vitro Testosterone Production, Sperm Motility, and Fertility in Chicken: Possible Involvement of Its Receptor CMKLR1. Cells 2020; 9:cells9071599. [PMID: 32630345 PMCID: PMC7408590 DOI: 10.3390/cells9071599] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 06/23/2020] [Accepted: 06/30/2020] [Indexed: 12/21/2022] Open
Abstract
The chemokine chemerin is a novel adipokine involved in the regulation of energy metabolism but also female reproductive functions in mammals. Its effects on male fertility are less studied. Here, we investigated the involvement of chemerin in chicken male reproduction. Indeed, the improvement of the sperm of roosters is a challenge for the breeders since the sperm quantity and quality have largely decreased for several years. By using specific chicken antibodies, here we show that chemerin and its main receptor CMKLR1 (chemokine-like receptor 1) are expressed within the chicken testis with the lowest expression in adults as compared to the embryo or postnatal stages. Chemerin and CMKLR1 are present in all testicular cells, including Leydig, Sertoli, and germinal cells. Using in vitro testis explants, we observed that recombinant chicken chemerin through CMKLR1 inhibits hCG (human chorionic gonadotropin) stimulated testosterone production and this was associated to lower 3βHSD (3beta-hydroxysteroid dehydrogenase) and StAR (steroidogenic acute regulatory protein) expression and MAPK ERK2 (Mitogen-Activated Protein Kinase Extracellular signal-regulated kinase 2) phosphorylation. Furthermore, we demonstrate that chemerin in seminal plasma is lower than in blood plasma, but it is negatively correlated with the percentage of motility and the spermatozoa concentration in vivo in roosters. In vitro, we show that recombinant chicken chemerin reduces sperm mass and individual motility in roosters, and this effect is abolished when sperm is pre-incubated with an anti-CMKLR1 antibody. Moreover, we demonstrate that fresh chicken sperm treated with chemerin and used for artificial insemination (AI) in hen presented a lower efficiency in terms of eggs fertility for the four first days after AI. Taken together, seminal chemerin levels are negatively associated with the rooster fertility, and chemerin produced locally by the testis or male tract could negatively affect in vivo sperm quality and testosterone production through CMKLR1.
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Brzoskwinia M, Pardyak L, Rak A, Kaminska A, Hejmej A, Marek S, Kotula-Balak M, Bilinska B. Flutamide Alters the Expression of Chemerin, Apelin, and Vaspin and Their Respective Receptors in the Testes of Adult Rats. Int J Mol Sci 2020; 21:E4439. [PMID: 32580404 PMCID: PMC7378763 DOI: 10.3390/ijms21124439] [Citation(s) in RCA: 15] [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: 05/05/2020] [Revised: 06/01/2020] [Accepted: 06/19/2020] [Indexed: 12/13/2022] Open
Abstract
Adipokines influence energy metabolism and have effects on male reproduction, including spermatogenesis and/or Sertoli cell maturation; however, the relationship between these active proteins and androgens in testicular cells is limited. Here, we studied the impact of short-term exposure to flutamide (an anti-androgen that blocks androgen receptors) on the expression of chemerin, apelin, vaspin and their receptors (CCRL2, CMKLR1, GPR1, APLNR, GRP78, respectively) in adult rat testes. Moreover, the levels of expression of lipid metabolism-modulating proteins (PLIN1, perilipin1; TSPO, translocator protein) and intercellular adherens junction proteins (nectin-2 and afadin) were determined in testicular cells. Plasma levels of adipokines, testosterone and cholesterol were also evaluated. Gene expression techniques used included the quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB) and immunohistochemistry (IHC). The androgen-mediated effects observed post-flutamide treatment were found at the gonadal level as chemerin, apelin, and vaspin gene expression alterations at mRNA and protein levels were detected, whereas the cellular targets for these adipokines were recognised by localisation of respective receptors in testicular cells. Plasma concentrations of all adipokines were unchanged, whereas plasma cholesterol content and testosterone level increased after flutamide exposure. Differential distribution of adipokine receptors indicates potential para- or autocrine action of the adipokines within the rat testes. Additionally, changes in the expression of PLIN1 and TSPO, involved in the initial step of testosterone synthesis in Leydig cells, suggest that testicular cells represent a target of flutamide action. Increase in the gene expression of PLIN1 and TSPO and higher total plasma cholesterol content indicates enhanced availability of cholesterol in Leydig cells as a result of androgen-mediated effects of flutamide. Alterations in adherens junction protein expression in the testis confirm the flutamide efficacy in disruption of androgen signalling and presumably lead to impaired para- and autocrine communication, important for proper functioning of adipokines.
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Affiliation(s)
- Malgorzata Brzoskwinia
- Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland; (M.B.); (L.P.); (A.K.); (A.H.); (S.M.)
| | - Laura Pardyak
- Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland; (M.B.); (L.P.); (A.K.); (A.H.); (S.M.)
| | - Agnieszka Rak
- Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland;
| | - Alicja Kaminska
- Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland; (M.B.); (L.P.); (A.K.); (A.H.); (S.M.)
| | - Anna Hejmej
- Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland; (M.B.); (L.P.); (A.K.); (A.H.); (S.M.)
| | - Sylwia Marek
- Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland; (M.B.); (L.P.); (A.K.); (A.H.); (S.M.)
| | - Malgorzata Kotula-Balak
- University Centre of Veterinary Medicine, University of Agriculture in Krakow, 30-059 Krakow, Poland;
| | - Barbara Bilinska
- Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland; (M.B.); (L.P.); (A.K.); (A.H.); (S.M.)
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Guo Y, Huo J, Wu D, Hao H, Ji X, Zhao E, Nie B, Liu Q. Simvastatin inhibits the adipogenesis of bone marrow‑derived mesenchymal stem cells through the downregulation of chemerin/CMKLR1 signaling. Int J Mol Med 2020; 46:751-761. [PMID: 32468037 PMCID: PMC7307816 DOI: 10.3892/ijmm.2020.4606] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 04/22/2020] [Indexed: 12/13/2022] Open
Abstract
Simvastatin is effective in the treatment of osteoporosis, partly through the inhibition of the adipogenesis of bone-marrow derived mesenchymal stem cells (BMSCs). The present study focused on the mechanisms responsible for the inhibitory effects of simvastatin on adipogenesis and examined the effects of simvastatin on the expression of peroxisome proliferator-activated receptor γ (PPARγ), chemerin, chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1) and the adipocyte marker gene, adiponectin. BMSCs were isolated from 4-week-old female Sprague-Dawley (SD) rats, and adipogenesis was measured by the absorbance values at 490 nm of Oil Red O dye. The expression of each gene was evaluated by western blot analysis or reverse transcription-quantitative PCR (RT-qPCR). The expression of chemerin increased during adipogenesis, while CMKLR1 exhibited a trend towards a decreased expression. On days 7 and 14, the simvastatin-treated cells exhibited a down-regulated expression of chemerin, whereas the upregulated expression of its receptor, CMKLR1 was observed. The results also revealed that CMKLR1 is required for adipogenesis and the simvastatin-mediated inhibitory effect on adipogenesis. Simvastatin regulated adipogenesis by negatively modulating chemerin-CMKLR1 signaling. Importantly, simvastatin stimulation inhibited the upregulation of PPARγ and PPARγ-mediated chemerin expression to prevent adipogenesis. Treatment with the PPARγ agonist, rosiglitazone, partially reversed the negative regulatory effects of simvastatin. On the whole, the findings of the present study demonstrate that simvastatin inhibits the adipogenesis of BMSCs through the downregulation of PPARγ and subsequently prevents the PPARγ-mediated induction of chemerin/CMKLR1 signaling.
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Affiliation(s)
- Yao Guo
- Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Jianzhong Huo
- Department of Orthopaedics, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030032, P.R. China
| | - Dou Wu
- Department of Orthopaedics, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030032, P.R. China
| | - Haihu Hao
- Department of Orthopaedics, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030032, P.R. China
| | - Xinghua Ji
- Department of Orthopaedics, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030032, P.R. China
| | - Enzhe Zhao
- Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Boyuan Nie
- Department of Orthopaedics, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
| | - Qiang Liu
- Department of Orthopaedics, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030032, P.R. China
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Abstract
PURPOSE OF THE REVIEW Osteoarthritis (OA) is an aging-associated and injury-induced joint disease characterized by cartilage degradation, bone sclerosis, and persistent low-grade inflammation in the joint. Aging and injury are triggers of joint pathological changes mediated by pro-inflammatory factors, some of which are secreted by white adipose tissue. Adipokines including adiponectin, leptin, resistin, chemerin, IL-6, and TNF-α are major players not only during inflammation but also in metabolic regulation of joint cells including chondrocytes, osteoblasts, osteoclasts as well as mesenchymal stem cells. The purpose of this review is to summarize the signal transduction pathways of adipokines in the articular joint to provide new information on potential targets for intervention of OA. RECENT FINDINGS The risk of knee osteoarthritis is associated with adipokine gene polymorphism. While the infrapatellar fat pad is a major source of adipokines in knee synovial fluid, adipocytes also accumulate in the bone marrow during aging and obesity. Adipokines can act as SASPs (senescence associated secretory phenotype factors) that participate in cellular senescence of chondrocytes, but they also regulate energy metabolism impacting bone remodeling. Thus, adipokines are closely related to the metabolic syndrome and degenerative pathological changes in cartilage and bone during OA. Modulating the effects of adipokines on different cell types in the intra-articular joint will be a promising new option for OA intervention.
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Affiliation(s)
- Chenxi Xie
- Bone and Joint Research Center, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Qian Chen
- Department of Orthopaedics, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, 02903, USA.
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Estienne A, Bongrani A, Reverchon M, Ramé C, Ducluzeau PH, Froment P, Dupont J. Involvement of Novel Adipokines, Chemerin, Visfatin, Resistin and Apelin in Reproductive Functions in Normal and Pathological Conditions in Humans and Animal Models. Int J Mol Sci 2019; 20:ijms20184431. [PMID: 31505789 PMCID: PMC6769682 DOI: 10.3390/ijms20184431] [Citation(s) in RCA: 120] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 09/06/2019] [Accepted: 09/06/2019] [Indexed: 12/23/2022] Open
Abstract
It is well known that adipokines are endocrine factors that are mainly secreted by white adipose tissue. Their central role in energy metabolism is currently accepted. More recently, their involvement in fertility regulation and the development of some reproductive disorders has been suggested. Data concerning the role of leptin and adiponectin, the two most studied adipokines, in the control of the reproductive axis are consistent. In recent years, interest has grown about some novel adipokines, chemerin, visfatin, resistin and apelin, which have been found to be strongly associated with obesity and insulin-resistance. Here, we will review their expression and role in male and female reproduction in humans and animal models. According to accumulating evidence, they could regulate the secretion of GnRH (Gonadotropin-Releasing Hormone), gonadotropins and steroids. Furthermore, their expression and that of their receptors (if known), has been demonstrated in the human and animal hypothalamo-pituitary-gonadal axis. Like leptin and adiponectin, these novel adipokines could thus represent metabolic sensors that are able to regulate reproductive functions according to energy balance changes. Therefore, after investigating their role in normal fertility, we will also discuss their possible involvement in some reproductive troubles known to be associated with features of metabolic syndrome, such as polycystic ovary syndrome, gestational diabetes mellitus, preeclampsia and intra-uterine growth retardation in women, and sperm abnormalities and testicular pathologies in men.
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Affiliation(s)
- Anthony Estienne
- INRA UMR 85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
- CNRS UMR 7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
- Université François Rabelais de Tours F-37041 Tours, France
- IFCE, F-37380 Nouzilly, France
| | - Alice Bongrani
- INRA UMR 85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
- CNRS UMR 7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
- Université François Rabelais de Tours F-37041 Tours, France
- IFCE, F-37380 Nouzilly, France
| | - Maxime Reverchon
- SYSAAF-Syndicat des Sélectionneurs Avicoles et Aquacoles Français, Centre INRA Val de Loire, F-37380 Nouzilly, France
| | - Christelle Ramé
- INRA UMR 85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
- CNRS UMR 7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
- Université François Rabelais de Tours F-37041 Tours, France
- IFCE, F-37380 Nouzilly, France
| | - Pierre-Henri Ducluzeau
- INRA UMR 85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
- CNRS UMR 7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
- Université François Rabelais de Tours F-37041 Tours, France
- IFCE, F-37380 Nouzilly, France
- Internal Medicine Department, Unit of Endocrinology, CHRU Tours, F-37044 Tours, France
| | - Pascal Froment
- INRA UMR 85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
- CNRS UMR 7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France
- Université François Rabelais de Tours F-37041 Tours, France
- IFCE, F-37380 Nouzilly, France
| | - Joëlle Dupont
- INRA UMR 85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- CNRS UMR 7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- Université François Rabelais de Tours F-37041 Tours, France.
- IFCE, F-37380 Nouzilly, France.
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The role of GPCRs in bone diseases and dysfunctions. Bone Res 2019; 7:19. [PMID: 31646011 PMCID: PMC6804689 DOI: 10.1038/s41413-019-0059-6] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Revised: 05/22/2019] [Accepted: 05/27/2019] [Indexed: 12/13/2022] Open
Abstract
The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals. Critical roles of GPCRs have been established in bone development, remodeling, and disease. Multiple human GPCR mutations impair bone development or metabolism, resulting in osteopathologies. Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals. To date, 92 receptors (5 glutamate family, 67 rhodopsin family, 5 adhesion, 4 frizzled/taste2 family, 5 secretin family, and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals). By analyzing data from these 92 GPCRs, we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions, and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models. Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD: 9 genes each for human height and osteoporosis; 4 genes each for human osteoarthritis (OA) and fracture risk; and 2 genes each for adolescent idiopathic scoliosis (AIS), periodontitis, osteosarcoma growth, and tooth development. Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass, while deficiency of 22 GPCRs increased bone mass and BMD; deficiency of 8 GPCRs reduced body length, while 5 mice had reduced femur size upon GPCR deletion. Furthermore, deficiency in 6 GPCRs induced osteoporosis; 4 induced osteoarthritis; 3 delayed fracture healing; 3 reduced arthritis severity; and reduced bone strength, increased bone strength, and increased cortical thickness were each observed in 2 GPCR-deficiency models. The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis, population studies, and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.
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