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Neamah AS, Wadan AHS, Lafta FM, Elakwa DES. The potential role of targeting the leptin receptor as a treatment for breast cancer in the context of hyperleptinemia: a literature review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:3451-3466. [PMID: 39565396 DOI: 10.1007/s00210-024-03592-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 10/31/2024] [Indexed: 11/21/2024]
Abstract
Since cancer is becoming a leading cause of death worldwide, efforts should be concentrated on understanding its underlying biological alterations that would be utilized in disease management, especially prevention strategies. Within this context, multiple bodies of evidence have highlighted leptin's practical and promising role, a peptide hormone extracted from adipose and fatty tissues with other adipokines, in promoting the proliferation, migration, and metastatic invasion of breast carcinoma cells. Excessive blood leptin levels and hyperleptinemia increase body fat content and stimulate appetite. Also, high leptin level is believed to be associated with several conditions, including overeating, emotional stress, inflammation, obesity, and gestational diabetes. It has been noted that when leptin has impaired signaling in CNS, causing the lack of its normal function in energy balance, it results in leptin resistance, leading to a rise in its concentration in peripheral tissues. Our research paper will shed highlighting on potentially targeting the leptin receptor and its cellular signaling in suppressing breast cancer progression.
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Affiliation(s)
- Abbas S Neamah
- Department of Biology, College of Sciences, University of Baghdad, Baghdad, Iraq.
| | - Al-Hassan Soliman Wadan
- Oral Biology Department, Faculty of Dentistry, Galala University, Galala Plateau, Attaka, Suez Governorate, 15888, Egypt
| | - Fadhel M Lafta
- Department of Biology, College of Sciences, University of Baghdad, Baghdad, Iraq
| | - Doha El-Sayed Elakwa
- Department of Biochemistry & Molecular Biology, Faculty of Pharmacy for Girls, Al-Azhar University, Cairo, Egypt
- Department of Biochemistry, Faculty of Pharmacy, Sinai University, Kantra Branch, Ismailia, Egypt
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2
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Wen Y, Ma L, Liu Y, Xiong H, Shi D. Decoding the enigmatic role of T-cadherin in tumor angiogenesis. Front Immunol 2025; 16:1564130. [PMID: 40230838 PMCID: PMC11994602 DOI: 10.3389/fimmu.2025.1564130] [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: 01/21/2025] [Accepted: 03/14/2025] [Indexed: 04/16/2025] Open
Abstract
The cadherin family, which includes T-cadherin, plays a significant role in angiogenesis, a critical process involved in tumor growth, metastasis, and recurrence. T-cadherin is extensively expressed in both normal and tumor vascular tissues and has been shown to facilitate the proliferation and migration of vascular cells in some studies. However, T-cadherin also exerts inhibitory effects on angiogenesis in various tumor tissues. The functional role of T-cadherin may vary depending on the tumor type and the interaction between tumor cells and vascular cells, suggesting that it acts as a modulator rather than a primary driver of angiogenesis. Additionally, T-cadherin exhibits distinct characteristics depending on the tumor microenvironment. This review provides an overview of recent research on the role of T-cadherin in tumor angiogenesis and discusses its potential as a diagnostic or therapeutic marker in the field of tumor biology.
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Affiliation(s)
- Yiyang Wen
- The Laboratory of Medical Mycology, Jining No.1 People’s Hospital, Jining, Shandong, China
- Department of Pathology, Jining No.1 People’s Hospital, Jining, Shandong, China
| | - Li Ma
- The Laboratory of Medical Mycology, Jining No.1 People’s Hospital, Jining, Shandong, China
| | - Yuanyuan Liu
- The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Huabao Xiong
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, Shandong, China
| | - Dongmei Shi
- Department of Pathology, Jining No.1 People’s Hospital, Jining, Shandong, China
- Department of Dermatology, Jining No.1 People’s Hospital, Jining, Shandong, China
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Zhang L, Xia Z, Li Z, Zhang J, Wang K, Wang W. Influence of body fat tissue on outcomes in patients undergoing hepatectomy or liver transplantation: a systematic review and meta-analysis. Int J Surg 2025; 111:1167-1181. [PMID: 38920322 PMCID: PMC11745742 DOI: 10.1097/js9.0000000000001864] [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: 04/24/2024] [Accepted: 06/08/2024] [Indexed: 06/27/2024]
Abstract
OBJECTIVE The purpose of this study is to investigate potential associations between body fat composition and postoperative outcomes in patients with hepatectomy or liver transplantation. METHODS Three online databases, including Embase, PubMed, and the Cochrane Library, were thoroughly searched for literature describing the relationship between body fat composition and outcomes of patients with liver surgery from the start of each database to 29 October 2023. The Newcastle-Ottawa Scale was used to rate the quality of the studies. RESULTS This analysis included a total of 29 articles with a combined patient cohort of 6435 individuals. The results demonstrated that patients with high intramuscular fat content (IMFC) had significantly inferior overall survival (OS) [hazard ratio (HR): 2.07, 95% CI: 1.69-2.53, P <0.001] and recurrence-free survival (RFS) (HR: 1.61, 95% CI: 1.20-2.16, P =0.002) and a higher risk of major complications (HR: 2.20, 95% CI: 1.59-3.05, P <0.001). We also found that the presence of high visceral-to-subcutaneous fat tissue ratio (VSR) in patients with liver surgery was significantly related to poorer OS (HR: 1.70, 95% CI: 1.44-2.00, P <0.001) and progression-free survival (PFS) (HR: 1.29, 95% CI: 1.11-1.50, P =0.001) and a higher major complication rate (HR: 2.31, 95% CI: 1.17-4.56, P =0.016). Besides, the synthesized findings indicated there is no significant correlation between visceral fat tissue and survival outcomes or postoperative complications. CONCLUSION In summary, preoperative IMFC and VSR have the potential to forecast poorer OS and RFS and a higher risk of complications for patients undergoing hepatectomy or liver transplantation.
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Affiliation(s)
- Lilong Zhang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan
- General Surgery Laboratory, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Zhijia Xia
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan
- Department of General, Visceral, and Transplant Surgery, Ludwig Maximilian University of Munich, Munich, Germany
| | - Zhongyi Li
- Department of General, Visceral, and Transplant Surgery, Ludwig Maximilian University of Munich, Munich, Germany
| | - Jing Zhang
- Division of Basic Biomedical Sciences, The University of South Dakota Sanford School of Medicine, Vermillion, South Dakota, USA
| | - Kunpeng Wang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan
- General Surgery Laboratory, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Weixing Wang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan
- General Surgery Laboratory, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
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4
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Lin Q, Li J, Sun Y, Abudousalamu Z, Xue M, Yao L, Chen M. Proteome-Wide Mendelian Randomization Analysis to Identify Potential Plasma Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer Subtypes. Int J Womens Health 2024; 16:2263-2279. [PMID: 39726690 PMCID: PMC11669594 DOI: 10.2147/ijwh.s491414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 12/05/2024] [Indexed: 12/28/2024] Open
Abstract
Background Epithelial ovarian cancer (EOC) remains an unmet medical challenge due to its insidious onset, atypical symptoms, and increasing resistance to conventional chemotherapeutic agents. It is imperative to explore novel biomarkers and generate innovative target drugs. Methods To identify potential proteins with causal association to EOC subtypes, we conducted a Mendelian Randomization (MR) analysis using 15,419 protein quantitative trait loci (pQTLs) associated with 2015 proteins. Bayesian colocalization analysis, Summary-data-based MR, and Heterogeneity in Dependent Instruments tests were employed for validation. Enrichment and druggability analyses were performed to assess the biological significance and therapeutic potential of identified proteins. Results Our analysis identified 455 unique proteins associated with at least one EOC subtype, with 14 protein-cancer associations confirmed by further validation. Ten proteins were prioritized as potential therapeutic targets, including α1B-glycoprotein (A1BG) and ephrin-A1 (EFNA1), which interact with the known drug targets human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor receptor (VEGFR). Conclusion This study elucidated the plasma proteins causally associated with EOC subtypes, potentially offering easily detectable biomarkers and promising therapeutic targets. A1BG and EFNA1 were identified as druggable targets and confirmed to correspond with current pharmacological targets. Targeting these proteins in drug development potentially offers an avenue for innovative treatment strategies.
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Affiliation(s)
- Qianhan Lin
- Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People’s Republic of China
| | - Jiajia Li
- Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People’s Republic of China
| | - Yating Sun
- Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People’s Republic of China
| | - Zulimire Abudousalamu
- Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People’s Republic of China
| | - Mengyang Xue
- Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People’s Republic of China
| | - Liangqing Yao
- Department of Gynecologic Oncology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510005, People’s Republic of China
| | - Mo Chen
- Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People’s Republic of China
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Liermann-Wooldrik KT, Kosmacek EA, Oberley-Deegan RE. Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression. Int J Mol Sci 2024; 25:12137. [PMID: 39596205 PMCID: PMC11594286 DOI: 10.3390/ijms252212137] [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: 10/07/2024] [Revised: 11/07/2024] [Accepted: 11/10/2024] [Indexed: 11/28/2024] Open
Abstract
Obesity is a common risk factor in multiple tumor types, including prostate cancer. Obesity has been associated with driving metastasis, therapeutic resistance, and increased mortality. The effect of adipose tissue on the tumor microenvironment is still poorly understood. This review aims to highlight the work conducted in the field of obesity and prostate cancer and bring attention to areas where more research is needed. In this review, we have described key differences between healthy adipose tissues and obese adipose tissues, as they relate to the tumor microenvironment, focusing on mechanisms related to metabolic changes, abnormal adipokine secretion, altered immune cell presence, and heightened oxidative stress as drivers of prostate cancer formation and progression. Interestingly, common treatment options for prostate cancer ignore the adipose tissue located near the site of the tumor. Because of this, we have outlined how excess adipose tissue potentially affects therapeutics' efficacy, such as androgen deprivation, chemotherapy, and radiation treatment, and identified possible drug targets to increase prostate cancer responsiveness to clinical treatments. Understanding how obesity affects the tumor microenvironment will pave the way for understanding why some prostate cancers become metastatic or treatment-resistant, and why patients experience recurrence.
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Affiliation(s)
| | | | - Rebecca E. Oberley-Deegan
- Department of Biochemistry and Molecular Biology, 985870 University of Nebraska Medical Center, Omaha, NE 68198, USA; (K.T.L.-W.)
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DeBari MK, Johnston EK, Scott JV, Ilzuka E, Sun W, Webster-Wood VA, Abbott RD. A Preliminary Study on Factors That Drive Patient Variability in Human Subcutaneous Adipose Tissues. Cells 2024; 13:1240. [PMID: 39120271 PMCID: PMC11311805 DOI: 10.3390/cells13151240] [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: 06/10/2024] [Revised: 07/15/2024] [Accepted: 07/19/2024] [Indexed: 08/10/2024] Open
Abstract
Adipose tissue is a dynamic regulatory organ that has profound effects on the overall health of patients. Unfortunately, inconsistencies in human adipose tissues are extensive and multifactorial, including large variability in cellular sizes, lipid content, inflammation, extracellular matrix components, mechanics, and cytokines secreted. Given the high human variability, and since much of what is known about adipose tissue is from animal models, we sought to establish correlations and patterns between biological, mechanical, and epidemiological properties of human adipose tissues. To do this, twenty-six independent variables were cataloged for twenty patients, which included patient demographics and factors that drive health, obesity, and fibrosis. A factorial analysis for mixed data (FAMD) was used to analyze patterns in the dataset (with BMI > 25), and a correlation matrix was used to identify interactions between quantitative variables. Vascular endothelial growth factor A (VEGFA) and actin alpha 2, smooth muscle (ACTA2) gene expression were the highest loadings in the first two dimensions of the FAMD. The number of adipocytes was also a key driver of patient-related differences, where a decrease in the density of adipocytes was associated with aging. Aging was also correlated with a decrease in overall lipid percentage of subcutaneous tissue, with lipid deposition being favored extracellularly, an increase in transforming growth factor-β1 (TGFβ1), and an increase in M1 macrophage polarization. An important finding was that self-identified race contributed to variance between patients in this study, where Black patients had significantly lower gene expression levels of TGFβ1 and ACTA2. This finding supports the urgent need to account for patient ancestry in biomedical research to develop better therapeutic strategies for all patients. Another important finding was that TGFβ induced factor homeobox 1 (TGIF1), an understudied signaling molecule, which is highly correlated with leptin signaling, was correlated with metabolic inflammation. Furthermore, this study draws attention to what we define as "extracellular lipid droplets", which were consistently found in collagen-rich regions of the obese adipose tissues evaluated here. Reduced levels of TGIF1 were correlated with higher numbers of extracellular lipid droplets and an inability to suppress fibrotic changes in adipose tissue. Finally, this study indicated that M1 and M2 macrophage markers were correlated with each other and leptin in patients with a BMI > 25. This finding supports growing evidence that macrophage polarization in obesity involves a complex, interconnecting network system rather than a full switch in activation patterns from M2 to M1 with increasing body mass. Overall, this study reinforces key findings in animal studies and identifies important areas for future research, where human and animal studies are divergent. Understanding key drivers of human patient variability is required to unravel the complex metabolic health of unique patients.
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Affiliation(s)
- Megan K. DeBari
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA; (M.K.D.); (E.K.J.); (J.V.S.); (E.I.); (V.A.W.-W.)
| | - Elizabeth K. Johnston
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA; (M.K.D.); (E.K.J.); (J.V.S.); (E.I.); (V.A.W.-W.)
| | - Jacqueline V. Scott
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA; (M.K.D.); (E.K.J.); (J.V.S.); (E.I.); (V.A.W.-W.)
| | - Erica Ilzuka
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA; (M.K.D.); (E.K.J.); (J.V.S.); (E.I.); (V.A.W.-W.)
- Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA;
| | - Wenhuan Sun
- Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA;
| | - Victoria A. Webster-Wood
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA; (M.K.D.); (E.K.J.); (J.V.S.); (E.I.); (V.A.W.-W.)
- Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA;
| | - Rosalyn D. Abbott
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA; (M.K.D.); (E.K.J.); (J.V.S.); (E.I.); (V.A.W.-W.)
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Zheng J, Zhang W, Xu R, Liu L. The role of adiponectin and its receptor signaling in ocular inflammation-associated diseases. Biochem Biophys Res Commun 2024; 717:150041. [PMID: 38710142 DOI: 10.1016/j.bbrc.2024.150041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/13/2024] [Accepted: 04/29/2024] [Indexed: 05/08/2024]
Abstract
Ocular inflammation-associated diseases are leading causes of global visual impairment, with limited treatment options. Adiponectin, a hormone primarily secreted by adipose tissue, binds to its receptors, which are widely distributed throughout the body, exerting powerful physiological regulatory effects. The protective role of adiponectin in various inflammatory diseases has gained increasing attention in recent years. Previous studies have confirmed the presence of adiponectin and its receptors in the eyes. Furthermore, adiponectin and its analogs have shown potential as novel drugs for the treatment of inflammatory eye diseases. This article summarizes the evidence for the interplay between adiponectin and inflammatory eye diseases and provides new perspectives on the diagnostic and therapeutic possibilities of adiponectin.
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Affiliation(s)
- Jing Zheng
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China; Department of Optometry and Visual Science, West China Hospital, Sichuan University, Chengdu, China
| | - Wenqiu Zhang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China; Department of Optometry and Visual Science, West China Hospital, Sichuan University, Chengdu, China
| | - Ran Xu
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China; Department of Optometry and Visual Science, West China Hospital, Sichuan University, Chengdu, China
| | - Longqian Liu
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China; Department of Optometry and Visual Science, West China Hospital, Sichuan University, Chengdu, China.
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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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Zuo L, Lin J, Ge S, Wu R, Liu B, Cheng Y, Tian Y. Preoperative visceral fat index predicts the survival outcomes of patients with gastric cancer after surgery. Oncol Lett 2024; 27:99. [PMID: 38298425 PMCID: PMC10829067 DOI: 10.3892/ol.2024.14233] [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: 07/09/2023] [Accepted: 11/27/2023] [Indexed: 02/02/2024] Open
Abstract
Visceral adipose tissue and skeletal muscle mass are associated with carcinogenesis and clinical outcomes in patients with cancer. The aim of the present study was to determine the influence of body composition parameters on postoperative survival in patients with gastric cancer. Demographic data and systemic inflammatory response data were obtained from patients with gastric cancer undergoing radical gastrectomy. The patient's skeletal muscle and visceral fat were assessed using computed tomography, and the corresponding skeletal muscle index (SMI) and visceral fat index (VFI) were calculated. Univariate and multivariate analyses were then performed. Of the 342 patients from whom information was collected, 125 of these patients eventually succumbed to the disease. A total of 271 (79.24%) of the patients were male and 71 (20.76%) were female. Regarding the entire cohort, the mean age was 64 years [interquartile range (IQR), 56-74 years], while the mean body mass index collected was 21.53 (IQR, 19.27-24.22). The median SMI and VFI of the patients were 47.73 (IQR, 41.67-55.51) and 41.28 (IQR, 36.62-45.36), respectively. It was concluded that a low SMI and VFI were associated with worse survival outcomes. However, the neutrophil-to-lymphocyte ratio and perioperative blood transfusion were not significantly associated with overall survival (OS). Among the indicators assessed, a low VFI was an independent risk factor associated with the worst OS time (hazard ratio 1.59; confidence interval, 1.03-2.45; P=0.038). Finally, a prognostic nomogram was constructed which included the VFI to assist clinicians in making more informed decisions. In conclusion, after data collection and analysis, it was found that there was a significant correlation between a low VFI and a shorter OS time in patients with gastric cancer following gastrectomy, suggesting that VFI may be a promising therapeutic target for postoperative interventions to improve patient survival further.
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Affiliation(s)
- Lugen Zuo
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China
| | - Jianxiu Lin
- First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Sitang Ge
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China
| | - Rong Wu
- Department of General Surgery, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210000, P.R. China
| | - Baoxinzi Liu
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine and Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China
| | - Ying Cheng
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine and Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China
| | - Yun Tian
- Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine and Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China
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Capuozzo M, Celotto V, Landi L, Ferrara F, Sabbatino F, Perri F, Cascella M, Granata V, Santorsola M, Ottaiano A. Beyond Body Size: Adiponectin as a Key Player in Obesity-Driven Cancers. Nutr Cancer 2023; 75:1848-1862. [PMID: 37873648 DOI: 10.1080/01635581.2023.2272343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/22/2023] [Accepted: 08/23/2023] [Indexed: 10/25/2023]
Abstract
Obesity, a complex and multifactorial disease influenced by genetic, environmental, and psychological factors, has reached epidemic proportions globally, posing a significant health challenge. In addition to its established association with cardiovascular disease and type II diabetes, obesity has been implicated as a risk factor for various cancers. However, the precise biological mechanisms linking obesity and cancer remain largely understood. Adipose tissue, an active endocrine organ, produces numerous hormones and bioactive molecules known as adipokines, which play a crucial role in metabolism, immune responses, and systemic inflammation. Notably, adiponectin (APN), the principal adipocyte secretory protein, exhibits reduced expression levels in obesity. In this scoping review, we explore and discuss the role of APN in influencing cancer in common malignancies, including lung, breast, colorectal, prostate, gastric, and endometrial cancers. Our review aims to emphasize the critical significance of investigating this field, as it holds great potential for the development of innovative treatment strategies that specifically target obesity-related malignancies. Furthermore, the implementation of more rigorous and comprehensive prevention and treatment policies for obesity is imperative in order to effectively mitigate the risk of associated diseases, such as cancer.
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Affiliation(s)
| | | | | | | | - Francesco Sabbatino
- Oncology Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Salerno, Italy
| | - Francesco Perri
- Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale", Naples, Italy
| | - Marco Cascella
- Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale", Naples, Italy
| | - Vincenza Granata
- Istituto Nazionale Tumori di Napoli, IRCCS "G. Pascale", Naples, Italy
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Begum M, Choubey M, Tirumalasetty MB, Arbee S, Mohib MM, Wahiduzzaman M, Mamun MA, Uddin MB, Mohiuddin MS. Adiponectin: A Promising Target for the Treatment of Diabetes and Its Complications. Life (Basel) 2023; 13:2213. [PMID: 38004353 PMCID: PMC10672343 DOI: 10.3390/life13112213] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 10/30/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, presents a formidable global health challenge with its associated complications. Adiponectin, an adipocyte-derived hormone, has emerged as a significant player in glucose metabolism and insulin sensitivity. Beyond its metabolic effects, adiponectin exerts anti-inflammatory, anti-oxidative, and vasoprotective properties, making it an appealing therapeutic target for mitigating diabetic complications. The molecular mechanisms by which adiponectin impacts critical pathways implicated in diabetic nephropathy, retinopathy, neuropathy, and cardiovascular problems are thoroughly examined in this study. In addition, we explore possible treatment options for increasing adiponectin levels or improving its downstream signaling. The multifaceted protective roles of adiponectin in diabetic complications suggest its potential as a novel therapeutic avenue. However, further translational studies and clinical trials are warranted to fully harness the therapeutic potential of adiponectin in the management of diabetic complications. This review highlights adiponectin as a promising target for the treatment of diverse diabetic complications and encourages continued research in this pivotal area of diabetes therapeutics.
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Affiliation(s)
- Mahmuda Begum
- Department of Internal Medicine, HCA-St David’s Medical Center, 919 E 32nd St, Austin, TX 78705, USA;
| | - Mayank Choubey
- Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, 101 Mineola Blvd, Mineola, NY 11501, USA; (M.C.); (M.B.T.); (M.W.)
| | - Munichandra Babu Tirumalasetty
- Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, 101 Mineola Blvd, Mineola, NY 11501, USA; (M.C.); (M.B.T.); (M.W.)
| | - Shahida Arbee
- Institute for Molecular Medicine, Aichi Medical University, 1-Yazako, Karimata, Aichi, Nagakute 480-1103, Japan;
| | - Mohammad Mohabbulla Mohib
- Julius Bernstein Institute of Physiology, Medical School, Martin Luther University of Halle-Wittenberg, Magdeburger Straße 6, 06112 Halle, Germany;
| | - Md Wahiduzzaman
- Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, 101 Mineola Blvd, Mineola, NY 11501, USA; (M.C.); (M.B.T.); (M.W.)
| | - Mohammed A. Mamun
- CHINTA Research Bangladesh, Savar 1342, Bangladesh;
- Department of Public Health and Informatics, Jahangirnagar University, Savar 1342, Bangladesh
| | - Mohammad Borhan Uddin
- Department of Pharmaceutical Sciences, North South University, Dhaka 1229, Bangladesh;
| | - Mohammad Sarif Mohiuddin
- Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, 101 Mineola Blvd, Mineola, NY 11501, USA; (M.C.); (M.B.T.); (M.W.)
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12
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Park J, Zhang H, Kwak HJ, Gadhe CG, Kim Y, Kim H, Noh M, Shin D, Ha SJ, Kwon YG. A novel small molecule, CU05-1189, targeting the pleckstrin homology domain of PDK1 suppresses VEGF-mediated angiogenesis and tumor growth by blocking the Akt signaling pathway. Front Pharmacol 2023; 14:1275749. [PMID: 38035024 PMCID: PMC10687218 DOI: 10.3389/fphar.2023.1275749] [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: 08/10/2023] [Accepted: 11/06/2023] [Indexed: 12/02/2023] Open
Abstract
Inhibition of angiogenesis is considered a promising therapeutic approach for cancer treatment. Our previous genetic research showed that the use of a cell-penetrating peptide to inhibit the pleckstrin homology (PH) domain of 3-phosphoinositide-dependent kinase 1 (PDK1) was a viable approach to suppress pathological angiogenesis. Herein, we synthesized and characterized a novel small molecule, CU05-1189, based on our prior study and present evidence for the first time that this compound possesses antiangiogenic properties both in vitro and in vivo. The computational analysis showed that CU05-1189 can interact with the PH domain of PDK1, and it significantly inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration, invasion, and tube formation in human umbilical vein endothelial cells without apparent toxicity. Western blot analysis revealed that the Akt signaling pathway was specifically inhibited by CU05-1189 upon VEGF stimulation, without affecting other VEGF receptor 2 downstream molecules or cytosolic substrates of PDK1, by preventing translocation of PDK1 to the plasma membrane. We also found that CU05-1189 suppressed VEGF-mediated vascular network formation in a Matrigel plug assay. More importantly, CU05-1189 had a good pharmacokinetic profile with a bioavailability of 68%. These results led to the oral administration of CU05-1189, which resulted in reduced tumor microvessel density and growth in a xenograft mouse model. Taken together, our data suggest that CU05-1189 may have great potential and be a promising lead as a novel antiangiogenic agent for cancer treatment.
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Affiliation(s)
- Jeongeun Park
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
| | - Haiying Zhang
- Department of Bio Research, Curacle Co., Ltd., Seoul, Republic of Korea
| | - Hyun Jung Kwak
- Department of Strategic Planning, Curacle Co., Ltd., Seoul, Republic of Korea
| | | | - Yeomyeong Kim
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
| | - Hyejeong Kim
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
| | - Minyoung Noh
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
| | - Dongyun Shin
- College of Pharmacy, Gachon University, Incheon, Republic of Korea
| | - Sang-Jun Ha
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
| | - Young-Guen Kwon
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
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13
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Khedr L, Khedr NF, Werida RH. Functional capacity and inflammatory biomarkers as predictors for right atrial volume index in COPD patients. Int J Cardiovasc Imaging 2023; 39:1493-1504. [PMID: 37217717 PMCID: PMC10427529 DOI: 10.1007/s10554-023-02871-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 05/05/2023] [Indexed: 05/24/2023]
Abstract
OBJECTIVE Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and right-heart complications. So, this study aimed to evaluate the role of right atrial volume index (RAVI), inflammatory biomarkers and functional capacity in predicting poor outcomes for patients with COPD, classified by COPD assessment test (CAT) questionnaire, as early predictors of right heart diseases. METHODS 151 patients with COPD with ejection fraction (LVEF) > 55% were enrolled and classified according to CAT questionnaire into CAT ≥ 10 (group I) and CAT < 10 (group II). RAVI was calculated using Echocardiography. Assessment of RV systolic function was done by Doppler imaging. Functional capacity parameters were assessed by modified medical research council dyspnea scale (mMRC). IL-1β, adiponectin, hs-CRP and neopterin were evaluated by ELSA kits. RESULTS Group I (CAT ≥ 10) had higher RAVI (73.92 ± 21.20 ml/m2 vs 22.73 ± 6.24 ml/m2, p < 0.001), lower S`tri (0.05 ± 0.01 vs 0.13 ± 0.03 m/s, p < 0.001), lower tricuspid annular plane systolic excursion (TAPSE) (1.20 ± 0.17 cm vs 2.17 ± 0.48 cm, p < 0.001), higher RVSP (54.88 ± 7.97 vs 26.79 ± 9.84 mmHg, p < 0.001) compared with group II (CAT < 10). RAVI was good predictor of CAT (r = 0.954, p < 0.001) and strongly correlated with tricuspid S`tri, RVSP, tricuspid E/e' and Mitral E/e' (r = -0.737, r = 0.753, r = 0.817 and r = 0.515, respectively, p < 0.001). RAVI was correlated with TAPSE (r = -0.673, p < 0.001) and with tricuspid E/A ratio & LVEF (r = 0.628, r = -0.407, respectively, p < 0.001). Hs-CRP: 2.50 ± 1.43 vs 2.03 ± 1.19, IL-1β: 37.96 ± 14.35 vs 27.57 ± 8.06, neopterin: 91.37 ± 17.30 vs 76.90 ± 16.75, p < 0.05) were significantly higher besides lower adiponectin levels (3.19 ± 1.98 vs 5.32 ± 1.33 p < 0.05) in group I as compared to group II. CONCLUSION Functional capacity might be useful predictor for right heart diseases in COPD patients. Inflammatory biomarkers, low adiponectin and high Hs-CRP, IL-1β and neopterin levels, might not only be useful to monitor treatment response but may also help to discriminate patients with a worsen prognosis.
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Affiliation(s)
- Lamiaa Khedr
- Department of Cardiology, Faculty of Medicine, Tanta University Hospital, Tanta University, Tanta, Egypt.
| | - Naglaa F Khedr
- Biochemistry Department, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt.
| | - Rehab H Werida
- Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour, 22514, Egypt.
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14
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Wang B, Du M. Increasing adipocyte number and reducing adipocyte size: the role of retinoids in adipose tissue development and metabolism. Crit Rev Food Sci Nutr 2023; 64:10608-10625. [PMID: 37427553 PMCID: PMC10776826 DOI: 10.1080/10408398.2023.2227258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/11/2023]
Abstract
The rising prevalence of obesity is a grave public health threat. In response to excessive energy intake, adipocyte hypertrophy impairs cellular function and leads to metabolic dysfunctions while de novo adipogenesis leads to healthy adipose tissue expansion. Through burning fatty acids and glucose, the thermogenic activity of brown/beige adipocytes can effectively reduce the size of adipocytes. Recent studies show that retinoids, especially retinoic acid (RA), promote adipose vascular development which in turn increases the number of adipose progenitors surrounding the vascular vessels. RA also promotes preadipocyte commitment. In addition, RA promotes white adipocyte browning and stimulates the thermogenic activity of brown/beige adipocytes. Thus, vitamin A is a promising anti-obesity micronutrient.
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Affiliation(s)
- Bo Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China
| | - Min Du
- Laboratory of Nutrigenomics and Growth Biology, Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA
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15
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Abdalla MMI, Mohanraj J, Somanath SD. Adiponectin as a therapeutic target for diabetic foot ulcer. World J Diabetes 2023; 14:758-782. [PMID: 37383591 PMCID: PMC10294063 DOI: 10.4239/wjd.v14.i6.758] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/25/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
The global burden of diabetic foot ulcers (DFUs) is a significant public health concern, affecting millions of people worldwide. These wounds cause considerable suffering and have a high economic cost. Therefore, there is a need for effective strategies to prevent and treat DFUs. One promising therapeutic approach is the use of adiponectin, a hormone primarily produced and secreted by adipose tissue. Adiponectin has demonstrated anti-inflammatory and anti-atherogenic properties, and researchers have suggested its potential therapeutic applications in the treatment of DFUs. Studies have indicated that adiponectin can inhibit the production of pro-inflammatory cytokines, increase the production of vascular endothelial growth factor, a key mediator of angiogenesis, and inhibit the activation of the intrinsic apoptotic pathway. Additionally, adiponectin has been found to possess antioxidant properties and impact glucose metabolism, the immune system, extracellular matrix remodeling, and nerve function. The objective of this review is to summarize the current state of research on the potential role of adiponectin in the treatment of DFUs and to identify areas where further research is needed in order to fully understand the effects of adiponectin on DFUs and to establish its safety and efficacy as a treatment for DFUs in the clinical setting. This will provide a deeper understanding of the underlying mechanisms of DFUs that can aid in the development of new and more effective treatment strategies.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Physiology, Human Biology Division, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Jaiprakash Mohanraj
- Department of Biochemistry, Human Biology Division, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Sushela Devi Somanath
- Department of Microbiology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
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16
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Okroj D, Rzepecka A, Kłosowski P, Babińska A, Sworczak K. Review of Diagnostic Modalities for Adrenal Incidentaloma. J Clin Med 2023; 12:jcm12113739. [PMID: 37297933 DOI: 10.3390/jcm12113739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 05/18/2023] [Accepted: 05/26/2023] [Indexed: 06/12/2023] Open
Abstract
Adrenal incidentalomas are common findings in clinical practice, with a prevalence of up to 4.2% in radiological studies. Due to the large number of focal lesions in the adrenal glands, it can be challenging to make a definitive diagnosis and determine the appropriate management. The purpose of this review is to present current diagnostic modalities used to preoperatively distinguish between adrenocortical adenoma (ACA) and adrenocortical cancer (ACC). Proper management and diagnosis are crucial in avoiding unnecessary adrenalectomies, which occur in over 40% of cases. A literature analysis was conducted to compare ACA and ACC using imaging studies, hormonal evaluation, pathological workup, and liquid biopsy. Before deciding on surgical treatment, the nature of the tumor can be accurately determined using noncontrast CT imaging combined with tumor size and metabolomics. This approach helps to narrow down the group of patients with adrenal tumors who require surgical treatment due to the suspected malignant nature of the lesion.
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Affiliation(s)
- Dominika Okroj
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland
| | - Agata Rzepecka
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland
| | - Przemysław Kłosowski
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland
| | - Anna Babińska
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland
| | - Krzysztof Sworczak
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland
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17
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Vliora M, Ravelli C, Grillo E, Corsini M, Flouris AD, Mitola S. The impact of adipokines on vascular networks in adipose tissue. Cytokine Growth Factor Rev 2023; 69:61-72. [PMID: 35953434 DOI: 10.1016/j.cytogfr.2022.07.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 07/21/2022] [Accepted: 07/21/2022] [Indexed: 02/07/2023]
Abstract
Adipose tissue (AT) is a highly active and plastic endocrine organ. It secretes numerous soluble molecules known as adipokines, which act locally to AT control the remodel and homeostasis or exert pleiotropic functions in different peripheral organs. Aberrant production or loss of certain adipokines contributes to AT dysfunction associated with metabolic disorders, including obesity. The AT plasticity is strictly related to tissue vascularization. Angiogenesis supports the AT expansion, while regression of blood vessels is associated with AT hypoxia, which in turn mediates tissue inflammation, fibrosis and metabolic dysfunction. Several adipokines can regulate endothelial cell functions and are endowed with either pro- or anti-angiogenic properties. Here we address the role of adipokines in the regulation of angiogenesis. A better understanding of the link between adipokines and angiogenesis will open the way for novel therapeutic approaches to treat obesity and metabolic diseases.
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Affiliation(s)
- Maria Vliora
- FAME Laboratory, Department of Exercise Science, University of Thessaly, Trikala, Greece; Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia, Italy
| | - Cosetta Ravelli
- Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia, Italy
| | - Elisabetta Grillo
- Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia, Italy
| | - Michela Corsini
- Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia, Italy
| | - Andreas D Flouris
- FAME Laboratory, Department of Exercise Science, University of Thessaly, Trikala, Greece
| | - Stefania Mitola
- Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia, Italy.
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18
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Tan SK, Hougen HY, Merchan JR, Gonzalgo ML, Welford SM. Fatty acid metabolism reprogramming in ccRCC: mechanisms and potential targets. Nat Rev Urol 2023; 20:48-60. [PMID: 36192502 PMCID: PMC10826284 DOI: 10.1038/s41585-022-00654-6] [Citation(s) in RCA: 54] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2022] [Indexed: 01/11/2023]
Abstract
Lipid droplet formation is a defining histological feature in clear-cell renal cell carcinoma (ccRCC) but the underlying mechanisms and importance of this biological behaviour have remained enigmatic. De novo fatty acid (FA) synthesis, uptake and suppression of FA oxidation have all been shown to contribute to lipid storage, which is a necessary tumour adaptation rather than a bystander effect. Clinical studies and mechanistic investigations into the roles of different enzymes in FA metabolism pathways have revealed new metabolic vulnerabilities that hold promise for clinical effect. Several metabolic alterations are associated with worse clinical outcomes in patients with ccRCC, as lipogenic genes drive tumorigenesis. Enzymes involved in the intrinsic FA metabolism pathway include FA synthase, acetyl-CoA carboxylase, ATP citrate lyase, stearoyl-CoA desaturase 1, cluster of differentiation 36, carnitine palmitoyltransferase 1A and the perilipin family, and each might be potential therapeutic targets in ccRCC owing to the link between lipid deposition and ccRCC risk. Adipokines and lipid species are potential biomarkers for diagnosis and treatment monitoring in patients with ccRCC. FA metabolism could potentially be targeted for therapeutic intervention in ccRCC as small-molecule inhibitors targeting the pathway have shown promising results in preclinical models.
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Affiliation(s)
- Sze Kiat Tan
- Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, USA
- Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Helen Y Hougen
- Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Jaime R Merchan
- Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA
| | - Mark L Gonzalgo
- Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA
| | - Scott M Welford
- Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, USA.
- Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
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19
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Yin T, Chen S, Zeng G, Yuan W, Lu Y, Zhang Y, Huang Q, Xiong X, Xu B, Huang Q. Angiogenesis-Browning Interplay Mediated by Asprosin-Knockout Contributes to Weight Loss in Mice with Obesity. Int J Mol Sci 2022; 23:16166. [PMID: 36555807 PMCID: PMC9783228 DOI: 10.3390/ijms232416166] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 12/09/2022] [Accepted: 12/15/2022] [Indexed: 12/23/2022] Open
Abstract
Asprosin (ASP) is a recently identified adipokine secreted by white adipose tissue (WAT). It plays important roles in the maintenance of glucose homeostasis in the fasting state and in the occurrence and development of obesity. However, there is no report on whether and how ASP would inhibit angiogenesis and fat browning in the mouse adipose microenvironment. Therefore, the study sought to investigate the effects of ASP-knockout on angiogenesis and fat browning, and to identify the interaction between them in the ASP-knockout mouse adipose microenvironment. In the experiments in vivo, the ASP-knockout alleviated the obesity induced by a high fat diet (HFD) and increased the expressions of the browning-related proteins including uncoupling protein 1 (UCP1), PRD1-BF-1-RIZ1 homologus domain-containing protein-16 (PRDM16) and PPAR gamma coactivator 1 (PGC1-α) and the endothelial cell marker (CD31). In the experiments in vitro, treatment with the conditional medium (CM) from ASP-knockout adipocytes (ASP-/--CM) significantly promoted the proliferation, migration and angiogenesis of vascular endothelial cells, and increased the expressions of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) pathway proteins. In addition, the treatment with CM from endothelial cells (EC-CM) markedly reduced the accumulation of lipid droplets and increased the expressions of the browning-related proteins and the mitochondrial contents. Moreover, the treatment with EC-CM significantly improved the energy metabolism in 3T3-L1 adipocytes. These results highlight that ASP-knockout can promote the browning and angiogenesis of WAT, and the fat browning and angiogenesis can interact in the mouse adipose microenvironment, which contributes to weight loss in the mice with obesity.
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Affiliation(s)
- Tingting Yin
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang 330006, China
- Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang 330006, China
| | - Sheng Chen
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang 330006, China
- Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang 330006, China
| | - Guohua Zeng
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang 330006, China
- Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang 330006, China
| | - Wanwan Yuan
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang 330006, China
- Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang 330006, China
| | - Yanli Lu
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang 330006, China
- Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang 330006, China
| | - Yanan Zhang
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang 330006, China
- Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang 330006, China
| | - Qianqian Huang
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang 330006, China
- Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang 330006, China
| | - Xiaowei Xiong
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang 330006, China
- Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang 330006, China
| | - Baohua Xu
- Jiangxi Province Key Laboratory of Laboratory Animal, Nanchang 330006, China
| | - Qiren Huang
- Key Provincial Laboratory of Basic Pharmacology, Nanchang University, Nanchang 330006, China
- Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang 330006, China
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20
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McClain KM, Sampson JN, Petrick JL, Mazzilli KM, Gerszten RE, Clish CB, Purdue MP, Lipworth L, Moore SC. Metabolomic Analysis of Renal Cell Carcinoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Metabolites 2022; 12:metabo12121189. [PMID: 36557227 PMCID: PMC9785244 DOI: 10.3390/metabo12121189] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 11/18/2022] [Accepted: 11/19/2022] [Indexed: 12/02/2022] Open
Abstract
Background: In the US in 2021, 76,080 kidney cancers are expected and >80% are renal cell carcinomas (RCCs). Along with excess fat, metabolic dysfunction is implicated in RCC etiology. To identify RCC-associated metabolites, we conducted a 1:1 matched case−control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: We measured 522 serum metabolites in 267 cases/control pairs. Cases were followed for a median 7.1 years from blood draw to diagnosis. Using conditional logistic regression, we computed adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing risk between 90th and 10th percentiles of log metabolite intensity, with the significance threshold at a false discovery rate <0.20. Results: Four metabolites were inversely associated with risk of RCC during follow-up—C38:4 PI, C34:0 PC, C14:0 SM, and C16:1 SM (ORs ranging from 0.33−0.44). Two were positively associated with RCC risk—C3-DC-CH3 carnitine and C5 carnitine (ORs = 2.84 and 2.83, respectively). These results were robust when further adjusted for metabolic risk factors (body mass index (BMI), physical activity, diabetes/hypertension history). Metabolites associated with RCC had weak correlations (|r| < 0.2) with risk factors of BMI, physical activity, smoking, alcohol, and diabetes/hypertension history. In mutually adjusted models, three metabolites (C38:4 PI, C14:0 SM, and C3-DC-CH3 carnitine) were independently associated with RCC risk. Conclusions: Serum concentrations of six metabolites were associated with RCC risk, and three of these had independent associations from the mutually adjusted model. These metabolites may point toward new biological pathways of relevance to this malignancy.
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Affiliation(s)
- Kathleen M. McClain
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
- Correspondence: ; Tel.: +240-276-6317
| | - Joshua N. Sampson
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
| | | | - Kaitlyn M. Mazzilli
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
| | - Robert E. Gerszten
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
| | - Clary B. Clish
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Mark P. Purdue
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
| | - Loren Lipworth
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Steven C. Moore
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
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21
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Aljutaily T, Rehan M, Moustafa MMA, Barakat H. Effect of Intermittent Fasting, Probiotic-Fermented Camel Milk, and Probiotic-Fermented Camel Milk Incorporating Sukkari Date on Diet-Induced Obesity in Rats. FERMENTATION-BASEL 2022; 8:619. [DOI: 10.3390/fermentation8110619] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Obesity causes metabolic syndrome disorders that are detrimental to health. The current study examined the effects of intermittent fasting (IF), fermented camel milk (FCM), and fermented camel milk incorporating 10% Sukkari date (FCM-D) on weight loss, blood profile, and antioxidant status in obese rats for 6 weeks. Subsequently, leptin and adiponectin levels and histopathological examination of adipose tissue were carried out. Results showed that IF with FCM or FCM-D decreased body weight by 0.92 and −5.45%, respectively. IF alone lowered non-fasting blood glucose (NFBG) and fasting blood glucose FBG after 6 weeks, whereas adding FCM or FCM-D reduced NFBG after 4 weeks. Intermittently fasting obese rats given FCM or FCM-D had the lowest blood glucose levels (BGL). The hypolipidemic effects of IF, FCM, and FCM-D on obese rats reduced triglycerides (TG), cholesterols (CHO), and their derivatives. FCM-D with IF presented a superior effect on lipid profile. A reduction rate of 40, 37, 66, and 40% for TG, CHO, low-density lipoprotein (LDL-c), and very low-density lipoprotein (VLDL-c), respectively, and an increase in HDL-C by 34% were noticed. Reductions of 40, 37, 66, and 40% for TG, CHO, LDL-c, and VLDL-c, respectively, and a 34% rise in high-density lipoprotein (HDL-C) were noted. Combining IF with FCM or FCM-D lowered the atherogenic index (AI) by 42% and 59%, respectively. Remarkably, treating rats with FCM+IF or FCM-D+IF effectively attenuated leptin and adiponectin levels. Malondialdehyde (MDA) was significantly decreased in a type-dependent manner. Implementing FCM-D or FCM with IF significantly attenuated reduced glutathione (GSH), superoxide dismutase (SOD), MDA, and catalase (CAT) levels. The most efficient treatment was giving FCM-D with IF. Histopathologically, adipocyte lipolysis increases free fatty acids (FFAs) and promotes inflammation. Only IF+FCM-D indicated no histopathological alteration except for a few focal areas of a few inflammatory cell infiltrations in the parenchyma. In conclusion, combining IF and Probiotic-FCM or Probiotic-FCM-D effectively accelerated weight loss, attenuated metabolic markers, and reversed histopathological alterations. Thus, IF combined with Probiotic-FCM or Probiotic-FCM-D is highly recommended for weight loss, strengthening antioxidative status, and preventing health disorders.
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Affiliation(s)
- Thamer Aljutaily
- Department of Food Science and Human Nutrition, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah 51452, Saudi Arabia
| | - Medhat Rehan
- Department of Plant Production and Protection, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah 51452, Saudi Arabia
- Department of Genetics, Faculty of Agriculture, Kafrelsheikh University, Kafr El-Sheikh 33516, Egypt
| | | | - Hassan Barakat
- Department of Food Science and Human Nutrition, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah 51452, Saudi Arabia
- Department of Food Technology, Faculty of Agriculture, Benha University, Moshtohor 13736, Egypt
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22
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Zhang Z, Du J, Xu Q, Xing C, Li Y, Zhou S, Zhao Z, Mu Y, Zhao Z(A, Cao S, Li F. Adiponectin Suppresses Metastasis of Nasopharyngeal Carcinoma through Blocking the Activation of NF-κB and STAT3 Signaling. Int J Mol Sci 2022; 23:12729. [PMID: 36361525 PMCID: PMC9658954 DOI: 10.3390/ijms232112729] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/17/2022] [Accepted: 10/20/2022] [Indexed: 09/10/2023] Open
Abstract
Adiponectin is an adipocytokine with anti-inflammatory and anticancer properties. Our previous study has shown that blood adiponectin levels were inversely correlated to the risk of nasopharyngeal carcinoma (NPC), and that adiponectin could directly suppress the proliferation of NPC cells. However, the effect of adiponectin on NPC metastasis remains unknown. Here, we revealed in clinical studies that serum adiponectin level was inversely correlated with tumor stage, recurrence, and metastasis in NPC patients, and that low serum adiponectin level also correlates with poor metastasis-free survival. Coculture with recombinant adiponectin suppressed the migration and invasion of NPC cells as well as epithelial-mesenchymal transition (EMT). In addition, recombinant adiponectin dampened the activation of NF-κB and STAT3 signaling pathways induced by adipocyte-derived proinflammatory factors such as leptin, IL-6, and TNF-α. Pharmacological activation of adiponectin receptor through its specific agonist, AdipoRon, largely stalled the metastasis of NPC cells. Taken together, these findings demonstrated that adiponectin could not only regulate metabolism and inhibit cancer growth, but also suppress the metastasis of NPC. Pharmacological activation of adiponectin receptor may be a promising therapeutic strategy to stall NPC metastasis and extend patients' survival.
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Affiliation(s)
- Zongmeng Zhang
- The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
| | - Jinlin Du
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Medical University, Dongguan 523808, China
| | - Qihua Xu
- The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
| | - Chaofeng Xing
- The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
| | - Yuyu Li
- The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
| | - Sujin Zhou
- The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
| | - Zhenggang Zhao
- The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
| | - Yunping Mu
- The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
| | - Zijian (Allan) Zhao
- The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
| | - Sumei Cao
- Department of Cancer Prevention Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Fanghong Li
- The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
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23
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Tsankof A, Tziomalos K. Adiponectin: A player in the pathogenesis of hormone-dependent cancers. Front Endocrinol (Lausanne) 2022; 13:1018515. [PMID: 36277714 PMCID: PMC9582436 DOI: 10.3389/fendo.2022.1018515] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 09/22/2022] [Indexed: 11/13/2022] Open
Abstract
Hormone-dependent cancers are a major cause of morbidity and mortality in both genders. Accumulating evidence suggest that adiponectin, an adipokine with multifaceted functions, is implicated in the pathogenesis of several malignancies. In the present review, we discuss the existing data regarding this relationship. Several observational studies showed that low adiponectin levels are associated with higher risk for breast, cervical, endometrial, ovarian and prostate cancer. A relationship between adiponectin and the aggressiveness of some of these tumors has also been reported. In vitro studies reported that adiponectin inhibits the proliferation and induces apoptosis of breast, cervical, endometrial, ovarian and prostate cancer cells. Given the high prevalence of these cancers and the substantial associated morbidity and mortality, the role of agents that increase adiponectin levels and/or stimulate its activity should be evaluated for the prevention and management of these common tumors.
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Affiliation(s)
| | - Konstantinos Tziomalos
- First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
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24
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Harris BHL, Macaulay VM, Harris DA, Klenerman P, Karpe F, Lord SR, Harris AL, Buffa FM. Obesity: a perfect storm for carcinogenesis. Cancer Metastasis Rev 2022; 41:491-515. [PMID: 36038791 PMCID: PMC9470699 DOI: 10.1007/s10555-022-10046-2] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 06/08/2022] [Indexed: 12/14/2022]
Abstract
Obesity-related cancers account for 40% of the cancer cases observed in the USA and obesity is overtaking smoking as the most widespread modifiable risk factor for carcinogenesis. Here, we use the hallmarks of cancer framework to delineate how obesity might influence the carcinogenic hallmarks in somatic cells. We discuss the effects of obesity on (a) sustaining proliferative signaling; (b) evading growth suppressors; (c) resisting cell death; (d) enabling replicative immortality; (e) inducing angiogenesis; (f) activating invasion and metastasis; (g) reprogramming energy metabolism; and (h) avoiding immune destruction, together with its effects on genome instability and tumour-promoting inflammation. We present the current understanding and controversies in this evolving field, and highlight some areas in need of further cross-disciplinary focus. For instance, the relative importance of the many potentially causative obesity-related factors is unclear for each type of malignancy. Even within a single tumour type, it is currently unknown whether one obesity-related factor consistently plays a predominant role, or if this varies between patients or, even in a single patient with time. Clarifying how the hallmarks are affected by obesity may lead to novel prevention and treatment strategies for the increasingly obese population.
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Affiliation(s)
- Benjamin H L Harris
- Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
- St Anne's College, 56 Woodstock Rd, Oxford, OX2 6HS, UK.
| | - Valentine M Macaulay
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, OX3 9DU, UK
| | | | - Paul Klenerman
- Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, OX1 3SY, UK
| | - Fredrik Karpe
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Department of Medicine, University of Oxford, Oxford, OX3 7LE, UK
| | - Simon R Lord
- Early Phase Clinical Trials Unit, Churchill Hospital, Oxford, OX3 7LE, UK
| | - Adrian L Harris
- Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK
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25
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Marley AR, Ryder JR, Turcotte LM, Spector LG. Maternal obesity and acute lymphoblastic leukemia risk in offspring: A summary of trends, epidemiological evidence, and possible biological mechanisms. Leuk Res 2022; 121:106924. [PMID: 35939888 DOI: 10.1016/j.leukres.2022.106924] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/13/2022] [Accepted: 08/01/2022] [Indexed: 10/16/2022]
Abstract
Acute lymphoblastic leukemia, a heterogenous malignancy characterized by uncontrolled proliferation of lymphoid progenitors and generally initiated in utero, is the most common pediatric cancer. Although incidence of ALL has been steadily increasing in recent decades, no clear reason for this trend has been identified. Rising concurrently with ALL incidence, increasing maternal obesity rates may be partially contributing to increasing ALL prevelance. Epidemiological studies, including a recent meta-analysis, have found an association between maternal obesity and leukemogenesis in offspring, although mechanisms underlying this association remain unknown. Therefore, the purpose of this review is to propose possible mechanisms connecting maternal obesity to ALL risk in offspring, including changes to fetal/neonatal epigenetics, altered insulin-like growth factor profiles and insulin resistance, modified adipokine production and secretion, changes to immune cell populations, and impacts on birthweight and childhood obesity/adiposity. We describe how each proposed mechanism is biologically plausible due to their connection with maternal obesity, presence in neonatal and/or fetal tissue, observation in pediatric ALL patients at diagnosis, and association with leukemogenesis, A description of ALL and maternal obesity trends, a summary of epidemiological evidence, a discussion of the pathway from intrauterine environment to subsequent malignancy, and propositions for future directions are also presented.
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Affiliation(s)
- Andrew R Marley
- Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, 420 Delaware St SE MMC 715, Minneapolis, MN 55455, USA.
| | - Justin R Ryder
- Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, 420 Delaware St SE MMC 715, Minneapolis, MN 55455, USA; Center for Pediatric Obesity Medicine, Department of Pediatrics, University of Minnesota, 2450 Riverside Ave S AO-102, Minneapolis, MN 55454, USA
| | - Lucie M Turcotte
- Division of Hematology/Oncology, Department of Pediatrics, University of Minnesota, 420 Delaware St SE MMC 484, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, 425 East River Parkway, Minneapolis, MN 55455, USA
| | - Logan G Spector
- Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, 420 Delaware St SE MMC 715, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, 425 East River Parkway, Minneapolis, MN 55455, USA
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26
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Luo L, Liu M. Adiponectin: friend or foe in obesity and inflammation. MEDICAL REVIEW (2021) 2022; 2:349-362. [PMID: 37724325 PMCID: PMC10388816 DOI: 10.1515/mr-2022-0002] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/27/2022] [Indexed: 09/20/2023]
Abstract
Adiponectin is an adipokine predominantly produced by fat cells, circulates and exerts insulin-sensitizing, cardioprotective and anti-inflammatory effects. Dysregulation of adiponectin and/or adiponectin signaling is implicated in a number of metabolic diseases such as obesity, insulin resistance, diabetes, and cardiovascular diseases. However, while the insulin-sensitizing and cardioprotective effects of adiponectin have been widely appreciated in the field, the obesogenic and anti-inflammatory effects of adiponectin are still of much debate. Understanding the physiological function of adiponectin is critical for adiponectin-based therapeutics for the treatment of metabolic diseases.
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Affiliation(s)
- Liping Luo
- Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
- Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Meilian Liu
- Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
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27
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Bushra S, Al-Sadeq DW, Bari R, Sahara A, Fadel A, Rizk N. Adiponectin Ameliorates Hyperglycemia-Induced Retinal Endothelial Dysfunction, Highlighting Pathways, Regulators, and Networks. J Inflamm Res 2022; 15:3135-3166. [PMID: 35662872 PMCID: PMC9156523 DOI: 10.2147/jir.s358594] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 05/04/2022] [Indexed: 12/25/2022] Open
Abstract
Background The pathophysiology of diabetic retinopathy (DR) is multifaced. A low level of circulating adiponectin (APN) in type 2 diabetes is associated with microvasculature complications, and its role in the evolution of DR is complex. Aim This study is designed to explore the potential impact of APN in the pathogenesis of DR, linking the changes in cellular and biological processes with the pathways, networks, and regulators involved in its actions. Methods Human microvascular retinal endothelial cells (HMRECs) were exposed to 30mM glucose (HG) and treated with globular adiponectin (30μg/mL) for 24 hours. The cells were evaluated for reactive oxidative stress (ROS) and apoptosis. RT-PCR profile arrays were utilized to evaluate the profile of genes involved in endothelial functions, angiogenesis, extracellular matrix, and adhesion molecules for hyperglycemic HMRECs treated with adiponectin. In addition, the barrier function, leukocyte migration, and angiogenesis were evaluated. The differential expressed genes (DEGs) were outlined, and bioinformatic analysis was applied. Results Adiponectin suppresses ROS production and apoptosis in HMRECs under HG conditions. Adiponectin improved migration and barrier functions in hyperglycemic cells. The bioinformatic analysis highlighted that the signaling pathways of integrin, HMGB1, and p38 AMPK, are mainly involved in the actions of APN on HMRECs. APN significantly affects molecular functions, including the adhesion of cells, chemotaxis, migration of WBCs, and angiogenesis. STAT3, NFKB, IKBKB, and mir-8 are the top upstream regulators, which affect the expressions of the genes of the data set, while TNF and TGFB1 are the top regulators. Conclusion Adiponectin significantly counteracts hyperglycemia at various cellular and molecular levels, reducing its impact on the pathophysiological progression towards DR in vitro using HMRECs. Adiponectin ameliorates inflammatory response, oxidative stress, and endothelial barrier dysfunction using a causal network of NFBk complex, TNF, and HMGB1 and integrin pathways.
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Affiliation(s)
- Sumbul Bushra
- Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, Doha, Qatar
| | - Duaa W Al-Sadeq
- Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, Doha, Qatar
| | - Redwana Bari
- Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, Doha, Qatar
| | - Afifah Sahara
- Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, Doha, Qatar
| | - Amina Fadel
- Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, Doha, Qatar
| | - Nasser Rizk
- Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, Doha, Qatar
- Biomedical Research Center (BRC), Qatar University, Doha, Qatar
- Correspondence: Nasser Rizk, Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, P.O. Box 2713, Doha, Qatar, Tel +974-4403-4786, Email
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28
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Bragina AE, Tarzimanova AI, Osadchiy KK, Rodionova YN, Kudryavtseva MG, Jafarova ZB, Bayutina DА, Podzolkov VI. Ectopic Fat Depots: Physiological Role And Impact On Cardiovascular Disease Continuum. RUSSIAN OPEN MEDICAL JOURNAL 2022. [DOI: 10.15275/rusomj.2022.0104] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Obesity is a non-infectious pandemic. The visceral distribution of adipose tissue is a significant factor in the development of cardiovascular diseases and their complications. Along with the visceral abdominal depot in omentum and subcutaneous tissue, there are other ectopic adipose tissue depots: epicardial adipose tissue (EAT), perivascular adipose tissue (PVAT) and perirenal adipose tissue. This article presents a review of the physiological role and molecular basis of the PVAT and EAT function in healthy, as well as in pathological, conditions; the interaction of adipokines and cytokines, their contribution to the development and progression of cardiovascular diseases. The review discusses well-known facts and controversial issues in this field. Comprehensive investigation of the mechanisms of vascular and myocardial pathology in obese people, along with identification of biomarkers for early prediction of cardiovascular complications, would contribute to the development of targeted preventive measures and choice of therapeutic strategies, which is consistent with the contemporary concept of personalized medicine. We have analyzed domestic and foreign literature sources in eLIBRARY and PubMed scientific libraries for the period of 2001-2020.
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Affiliation(s)
- Anna E. Bragina
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Aida I. Tarzimanova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Konstantin K. Osadchiy
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Yulia N. Rodionova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Maria G. Kudryavtseva
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Zarema B. Jafarova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Darya А. Bayutina
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Valeriy I. Podzolkov
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
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29
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The interaction between glycemic index, glycemic load, and the genetic variant ADIPOQ T45G (rs2241766) in the risk of colorectal cancer: a case-control study in a Korean population. Eur J Nutr 2022; 61:2601-2614. [PMID: 35243553 DOI: 10.1007/s00394-022-02845-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 02/16/2022] [Indexed: 11/04/2022]
Abstract
PURPOSE The glycemic index (GI), glycemic load (GL), and adiponectin level contribute to glycemic response and insulin sensitivity in the body. Studies have shown that tumor development is related to glycemic disorders; however, the results are contradictory. We aimed to investigate the association of GI and GL with colorectal cancer (CRC) risk in a Korean population and their possible interactions with the genetic variant ADIPOQ T45G. METHODS AND RESULTS A case-control study including 2096 participants with 695 CRC cases was conducted. The results showed that diets with high GI or GL were significantly associated with an increased risk of CRC [odds ratio (OR) = 5.44, 95% confidence interval (CI) 3.85-7.68; OR = 4.43, 95% CI 3.18-6.15, respectively; all p-trends < 0.001]. Moreover, even with a low-GI and low-GL diet, G/G genotype carriers may have 2.93-fold and 3.77-fold higher risk of rectal cancer compared to carriers of other genotypes (T/T + T/G), (OR = 2.93, 95% CI 1.01-8.59, p-interaction = 0.011 for GI; OR = 3.77, 95% CI 1.46-9.77, p-interaction = 0.025 for GL). CONCLUSIONS Overall, our study suggests positive associations of GI and GL with CRC risk. Moreover, the associations of GI and GL with rectal cancer risk could be modified by ADIPOQ T45G in a Korean population. Further studies with larger sample sizes are needed to confirm our findings.
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30
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Liu Y, Li Y, Liang J, Sun Z, Wu Q, Liu Y, Sun C. Leptin: an entry point for the treatment of peripheral tissue fibrosis and related diseases. Int Immunopharmacol 2022; 106:108608. [PMID: 35180626 DOI: 10.1016/j.intimp.2022.108608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 01/24/2022] [Accepted: 02/02/2022] [Indexed: 11/26/2022]
Abstract
Leptin is a small peptide mainly secreted by adipocyte, which acts on the central nervous system of the hypothalamus to regulate the body's energy balance by inhibiting food intake, it also can directly act on specific cells through leptin receptors (for example, ObRa, which exists in the blood-brain barrier or kidneys), thereby affect cell metabolism. Excessive deposition of extracellular matrix (ECM) causes damage to normal tissues or destruction of organ structure, which will eventually lead to tissue or organ fibrosis. The sustainable development of fibrosis can lead to structural damage and functional decline of organs, and even exhaustion, which seriously threatens human health and life. In recent years, studies have found that leptin directly alleviates the fibrosis process of various tissues and organs in mammals. Therefore, we speculate that leptin may become a significant treatment for fibrosis of various tissues and organs in the future. So, the main purpose of this review is to explore the specific mechanism of leptin in the process of fibrosis in multiple tissues and organs, and to provide a theoretical basis for the treatment of various tissues and organs fibrosis and related diseases caused by it, which is of great significance in the future.
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Affiliation(s)
- Yuexia Liu
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
| | - Yizhou Li
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
| | - Juntong Liang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
| | - Zhuwen Sun
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
| | - Qiong Wu
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China; Medical College, Qinghai University, Xining, 810000, China.
| | - Yongnian Liu
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China; Medical College, Qinghai University, Xining, 810000, China.
| | - Chao Sun
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
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31
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Flores R, Ramirez M, Ayala L, Benavides EA, Xie F, Arellano AA, Stanko RL, Garcia MR. Adiponectin Influences FGF2 in the Developing Porcine Corpus Luteum. Vet Sci 2022; 9:vetsci9020077. [PMID: 35202330 PMCID: PMC8875662 DOI: 10.3390/vetsci9020077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/08/2022] [Accepted: 02/09/2022] [Indexed: 01/27/2023] Open
Abstract
Luteal angiogenesis is regulated by pro-angiogenic hormones including fibroblast growth factor 2 (FGF2) and angiopoietin 1 (Ang1), which are regulated by the adipokine leptin during development. Another adipokine, adiponectin, exhibits an inverse relationship with leptin and has been identified in the CL. Therefore, it is hypothesized that adiponectin will influence pro-angiogenic hormones in the developing porcine CL. Crossbred sows were randomly allocated to one of two days of the estrous cycle, day 5 (D5; n = 4) or day 7 (D7; n = 5) for CL collection. Tissue was processed for immunohistochemical localization of adiponectin receptor 2 (AdipoR2), gene expression of FGF2, Ang1, leptin, AdipoR2, and cell culture for adiponectin treatment. The expression of AdipoR2 tended (p = 0.09) to be higher in D7 lutea and was more prevalently localized to the cell surface of large and small luteal cells than in D5 tissue. Adiponectin influenced (p ≤ 0.05) FGF2, leptin, and AdipoR2 gene expression relative to the dose and day (D5 or D7). Collectively, the evidence supports the supposition that adiponectin influences angiogenic factors in the developing CL.
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Affiliation(s)
- Rita Flores
- Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078, USA;
| | - Martha Ramirez
- Department of Animal Science and Veterinary Technology, Texas A&M University-Kingsville, Kingsville, TX 78363, USA; (M.R.); (L.A.); (R.L.S.)
| | - Luis Ayala
- Department of Animal Science and Veterinary Technology, Texas A&M University-Kingsville, Kingsville, TX 78363, USA; (M.R.); (L.A.); (R.L.S.)
| | | | - Fang Xie
- Department of Surgery, University of California-San Francisco, San Francisco, CA 94142, USA;
| | - Adrian Aaron Arellano
- College of Veterinary Medicine, College Station, Texas A&M University, Corpus Christi, TX 77843, USA;
| | - Randy Louis Stanko
- Department of Animal Science and Veterinary Technology, Texas A&M University-Kingsville, Kingsville, TX 78363, USA; (M.R.); (L.A.); (R.L.S.)
| | - Michelle Renee Garcia
- Department of Animal Science and Veterinary Technology, Texas A&M University-Kingsville, Kingsville, TX 78363, USA; (M.R.); (L.A.); (R.L.S.)
- Correspondence: ; Tel.: +1-361-593-3197
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32
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Abbaszadegan MR, Mojarrad M, Rahimi HR, Moghbeli M. Genetic and molecular biology of gastric cancer among Iranian patients: an update. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2022. [DOI: 10.1186/s43042-022-00232-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Abstract
Background
There is a declining trend of gastric cancer (GC) incidence in the world during recent years that is related to the development of novel diagnostic methods. However, there is still a high ratio of GC mortality among the Iranian population that can be associated with late diagnosis. Despite various reports about the novel diagnostic markers, there is not any general and standard diagnostic panel marker for Iranian GC patients. Therefore, it is required to determine an efficient and general panel of molecular markers for early detection.
Main body of the abstract
In the present review, we summarized all of the reported markers until now among Iranian GC patients to pave the way for the determination of a population-based diagnostic panel of markers. In this regard, we categorized these markers in different groups based on their involved processes to know which molecular process is more frequent during the GC progression among Iranians.
Conclusion
We observed that the non-coding RNAs are the main factors involved in GC tumorigenesis in this population.
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33
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Bou Malhab LJ, Abdel-Rahman WM. Obesity and Inflammation: Colorectal Cancer Engines. Curr Mol Pharmacol 2022; 15:620-646. [PMID: 34488607 DOI: 10.2174/1874467214666210906122054] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 05/14/2021] [Accepted: 05/17/2021] [Indexed: 12/24/2022]
Abstract
The prevalence of obesity continues to increase to the extent that it became a worldwide pandemic. An accumulating body of evidence has associated obesity with the development of different types of cancer, including colorectal cancer, which is a notorious disease with a high mortality rate. At the molecular level, colorectal cancer is a heterogenous disease characterized by a myriad of genetic and epigenetic alterations associated with various forms of genomic instability (detailed in Supplementary Materials). Recently, the microenvironment has emerged as a major factor in carcinogenesis. Our aim is to define the different molecular alterations leading to the development of colorectal cancer in obese patients with a focus on the role of the microenvironment in carcinogenesis. We also highlight all existent molecules in clinical trials that target the activated pathways in obesity-associated colorectal cancer, whether used as single treatments or in combination. Obesity predisposes to colorectal cancer via creating a state of chronic inflammation with dysregulated adipokines, inflammatory mediators, and other factors such as immune cell infiltration. A unifying theme in obesity-mediated colorectal cancer is the activation of the PI3K/AKT, mTOR/MAPK, and STAT3 signaling pathways. Different inhibitory molecules towards these pathways exist, increasing the therapeutic choice of obesity-associated colon cancer. However, obese patients are more likely to suffer from chemotherapy overdosing. Preventing obesity through maintaining a healthy and active lifestyle remains to be the best remedy.
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Affiliation(s)
- Lara J Bou Malhab
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
| | - Wael M Abdel-Rahman
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
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34
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Liu J, Bao J, Zhang W, Li Q, Hou J, Wei X, Huang Y. The Potential of Visceral Adipose Tissue in Distinguishing Clear Cell Renal Cell Carcinoma from Renal Angiomyolipoma with Minimal Fat. Cancer Manag Res 2021; 13:8907-8914. [PMID: 34876853 PMCID: PMC8643137 DOI: 10.2147/cmar.s336920] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 11/13/2021] [Indexed: 01/05/2023] Open
Abstract
Purpose To overcome the challenge of preoperative differentiation between clear cell renal cell carcinoma (ccRCC) and renal angiomyolipoma with minimal fat (RMFAML), we evaluated the potential of visceral adipose tissue (VAT) in distinguishing RMFAML from ccRCC. Patients and Methods Patients (191) were divided into ccRCC and RMFAML groups according to postoperative pathology. Umbilical horizontal computed tomography (CT) images were used for visceral fat area (VFA), subcutaneous fat area (SFA) and total fat area (TFA) measurements. Logistic regression was used to identify risk factors for ccRCC. Areas under the receiver operating characteristic (ROC) curve (AUCs) were compared to identify the most valuable indicator for identifying ccRCC and RMFAML. Results In total, 166 patients had ccRCC, and 25 had RMFAML. ccRCC and RMFAML patients showed significant differences in age (P<0.001), sex (P<0.001), hypertension (P=0.027), BMI (P<0.001), SFA (P=0.046), VFA (P<0.001) and TFA (P<0.001). According to multiple logistic regression analysis, male sex [4.311 (1.469~12.653), p=0.008]; older age [1.047 (1.008~1.088), p=0.017]; and higher BMI [1.305 (1.088~1.566), p=0.004], SFA [1.013 (1.003~1.023), p=0.008], VFA [1.026 (1.012~1.041), p<0.001] and TFA [1.011 (1.005~1.017), p=0.001] were associated with ccRCC. The AUCs of sex (male), age, BMI, TFA, VFA, and SFA were 0.726, 0.687, 0.783, 0.769, 0.840, and 0.645, respectively. The VFA cut-off value was 69.99 cm2. The sensitivity and specificity of higher VFA (≥69.99 cm2) for ccRCC diagnosis were 79.52% and 80.00%, respectively. Conclusion In differentiating ccRCC from RMFAML, male sex, older age, and higher BMI, TFA, SFA, and VFA are risk factors for ccRCC. VFA is the most effective indicator for identifying ccRCC.
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Affiliation(s)
- Jianhu Liu
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China.,Department of Urology, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, 215300, People's Republic of China
| | - Jie Bao
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China
| | - Weijie Zhang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China
| | - Qiaoxing Li
- Department of Urology, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, 215300, People's Republic of China
| | - Jianquan Hou
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China
| | - Xuedong Wei
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China
| | - Yuhua Huang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China
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O'Connell F, O'Sullivan J. Help or hindrance: The obesity paradox in cancer treatment response. Cancer Lett 2021; 522:269-280. [PMID: 34534616 DOI: 10.1016/j.canlet.2021.09.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 09/09/2021] [Accepted: 09/13/2021] [Indexed: 12/20/2022]
Abstract
Obesity is a rising epidemic, the influence of which on cancer development, progression as well as its impact on current standard of care cancer treatments is profound with many facets. Obesity is emerging as a modulating factor in many cancer therapies, such as chemotherapy, radiotherapy, immunotherapy and combination therapies. It has been reported to diminish the efficacy of some treatments but has also been alluded to being protective in terms of reduced treatment toxicities, thus the evolution of the obesity paradox. The obese tumour microenvironment influences treatment response through modulation of a series of aspects, including altered adipocyte secretome, angiogenesis, hypoxia, fibrosis, free fatty acid uptake as well as a modulated immune landscape. However, the influence of these underlying mechanisms on cancer treatment response and the biological action of adipose tissue is still largely unknown. Elucidation of these facets may lead to the enhanced efficacy of current treatment options or the identification of novel methods to combat cancer in the obese tumour microenvironment.
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Affiliation(s)
- Fiona O'Connell
- Trinity St. James's Cancer Institute, Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St James's Hospital, Dublin 8, Ireland
| | - Jacintha O'Sullivan
- Trinity St. James's Cancer Institute, Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St James's Hospital, Dublin 8, Ireland.
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Podzolkov VI, Bragina AE, Osadchiy KK, Rodionova YN, Jafarova ZB, Lobanova MV, Larionova YS. Relationship between the volume of perivascular adipose tissue and the vascular wall lesion. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2021. [DOI: 10.15829/1728-8800-2021-2993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Aim. To study the relationship between the volume of perivascular adipose tissue (PVAT) and the vascular wall lesion.Material and methods. The study included 318 patients without cardiovascular disease (mean age, 63,5±13,7 years). Hypertension was detected in 268 (84,3%) patients. All patients underwent assessment of anthropometric characteristics, lipid profile, arterial wall stiffness with the estimation of cardio-ankle vascular index, intima-media thickness, brachial artery endothelial vasomotor function. Chest computed tomography was performed with the estimation of the volumes of PVAT and pericardial adipose tissue (PAT).Results. The volume of PVAT, on average, was 0,3 [0,2; 0,4] cm3 . The VAT volume was significantly higher in obese individuals when compared with patients with normal body weight: 0,4 [0,3; 0,5] vs 0,25 [0,2; 0,4] cm3 (p=0,0007). The VAT volume was higher in individuals with an increased CAVI level when compared with patients with normal CAVI values: 0,4 [0,3; 0,5] vs 0,3 [0,25; 0,3] (p=0,02). A significant correlation was found between the VAT volume and body mass index (r=0,27, p<0,005), waist circumference (r=0,41, p<0,005), CAVI (r=0,49, p<0,05), impaired endothelium-dependent brachial artery vasodilation (r=0,38, p<0,05). When performing multiple linear regression, a significant relationship of CAVI was found with age (β±SE, 0,51±0,15; p=0,002) and volume of PVAT (β±SE, 0,41±0,13; p=0,005).Conclusion. The results indicate the relationship of PVAT with visceral obesity and vascular wall stiffness parameters.
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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: 14] [Impact Index Per Article: 3.5] [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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Okubo S, Shindoh J, Kobayashi Y, Umino R, Akabane M, Kojima K, Hashimoto M. Adipose Tissue Distribution Predicts Prognosis of Cirrhotic Patients Undergoing Hepatectomy for Hepatocellular Carcinoma. Ann Surg Oncol 2021; 28:6738-6746. [PMID: 33554286 DOI: 10.1245/s10434-021-09658-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/09/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND Body composition data are reportedly correlated with patient prognosis for various cancers. However, little is known about the prognostic impact of adipose tissue distribution among patients with hepatocellular carcinoma (HCC). METHODS Data for 181 consecutive cirrhotic patients who underwent hepatectomy for HCC were retrospectively reviewed. The clinical significance of the visceral-to-subcutaneous adipose tissue ratio (VSR) was investigated through analysis of short- and long-term surgical outcomes. RESULTS Of the 181 patients, 60 (33%) were classified as the high-VSR group and 121 (67%) as the low-VSR group. Although VSR was not correlated with a risk of postoperative morbidity, multivariate analysis confirmed that a higher VSR was significantly correlated with a shorter time to interventional failure (hazard ratio [HR] 2.24; P = 0.008) and overall survival (HR 2.65; P = 0.001) independently of American Joint Committed on Cancer stage or preoperative nutritional status. Analysis of the recurrence patterns showed that the proportion of unresectable recurrence at the initial recurrence event was significantly higher in the high-VSR group (39% vs. 18%; P = 0.025). The yearly transition probabilities, defined by a Markov model from postoperative R0 status to advanced disease or death (7.6% vs. 1.5%, P < 0.001) and early recurrence stage to advanced disease or death (15.4% vs. 2.8%, P = 0.004), were higher in the high-VSR group, suggesting that patients with a higher VSR are vulnerable to disease progression. CONCLUSION A high VSR was found to be an independent predictor of disease progression and poor prognosis for HCC patients with underlying liver cirrhosis having resection for HCC.
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Affiliation(s)
- Satoshi Okubo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Junichi Shindoh
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | - Yuta Kobayashi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Ryosuke Umino
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Miho Akabane
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Kazutaka Kojima
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Masaji Hashimoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
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Fragkoulis C, Glykas I, Tzelves L, Stasinopoulos K, Lazarou L, Kaoukis A, Dellis A, Stathouros G, Papadopoulos G, Ntoumas K. Association of metabolic syndrome with prostate cancer diagnosis and aggressiveness in patients undergoing transrectal prostate biopsy. Arch Ital Urol Androl 2021; 93:291-295. [PMID: 34839634 DOI: 10.4081/aiua.2021.3.291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 07/10/2021] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION AND OBJECTIVE Even though the only established risk factors for prostate cancer (PCa) are age, ethnic origin and family history, there are data suggesting that environmental factors, such as the presence of metabolic syndrome (MetS), may also play a role in the etiology of the disease. The aim of this study is to correlate MetS with PCa diagnosis and Gleason score (GS) in patients undergoing transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS This is a prospective, single-center study including 378 patients who underwent transrectal ultrasound guided prostate biopsy in our department during the years from 2018 to 2019. Patients were divided into two groups according to the presence of PCa. Group A included 197 patients diagnosed with PCa while Group B consisted of 181 patients without PCa in their biopsy result. Multiple variables such as the presence of MetS and its components were evaluated in correlation to the presence of PCa and PCa characteristics. Statistical analysis was performed using the IBM SPSS Statistics v.23 program. RESULTS Mean PSA value was 8.7 ng/dl in the PCa group and 7.1 ng/dl in the non PCa group, respectively. MetS was diagnosed in 108 patients (54.8%) with PCa and 80 patients (44.2%) without PCa and the difference was statistically significant. Hypertriglyceridemia was the MetS component with statistically higher frequency in PCa patients. Furthermore, the prevalence of MetS was higher in higher Gleason score PCa (GS ≥ 4+3) patients vs lower Gleason score PCa (GS ≤ 3+4) patients. More specifically, MetS, hypertriglyceridemia, and low HDL levels were independent factors associated with higher Gleason score PCa (GS ≥ 4+3). CONCLUSIONS Patients suffering from MetS who undergo prostate biopsy present with higher rates of PCa diagnosis and higher GS in comparison with patients with a normal metabolic profile.
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Affiliation(s)
| | - Ioannis Glykas
- Department of Urology, General Hospital of Athens ''G. Gennimatas'', Athens.
| | - Lazaros Tzelves
- 2nd Department of Urology, National and Kapodistrian University of Athens, School of Medicine, Sismanoglio Hospital, Athens.
| | | | - Lazaros Lazarou
- 2nd Department of Urology, National and Kapodistrian University of Athens, School of Medicine, Sismanoglio Hospital, Athens.
| | - Andreas Kaoukis
- Department of Cardiology, General Hospital of Athens ''G. Gennimatas'', Athens.
| | - Athanasios Dellis
- 2nd Department of Surgery, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens.
| | - Georgios Stathouros
- Department of Urology, General Hospital of Athens ''G. Gennimatas'', Athens.
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Ghidini M, Ramai D, Facciorusso A, Singh J, Tai W, Rijavec E, Galassi B, Grossi F, Indini A. Metabolic disorders and the risk of cholangiocarcinoma. Expert Rev Gastroenterol Hepatol 2021; 15:999-1007. [PMID: 34423721 DOI: 10.1080/17474124.2021.1946393] [Citation(s) in RCA: 8] [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: 04/05/2021] [Accepted: 06/18/2021] [Indexed: 12/14/2022]
Abstract
Introduction: Cholangiocarcinoma (CCA) is a malignancy which arises from the biliary epithelium. Carcinogenesis of CCA is mainly linked to aberrant glucose metabolism and creation of an immunosuppressive environment around normal biliary epithelium. The incidence of CCA is higher in the East due to Opisthorchis viverrini, an endemic liver fluke. CCA has also be attributed to genetic, metabolic, and lifestyle risk factors.Areas covered: Differences in epidemiological risk factors are associated with varying phenotypes of CCA. Metabolic risk factors include diabetes, obesity, nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), dyslipidemia, and metabolic syndrome. Inherited metabolic risk factors include Wilson's disease and hemochromatosis. Metabolic disease is associated with a higher risk of CCA, with higher risk for the intrahepatic form. In this review, the authors provide an overview of available evidence regarding metabolic conditions associated with the development of CCA.Expert opinion: Metabolic disease is associated with a higher risk of intrahepatic CCA compared to its extrahepatic or hilar counterpart. As rates of obesity and metabolic syndrome increase, particularly in the West, it is conceivable that the incidence of CCA will also rise in the next years.
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Affiliation(s)
- Michele Ghidini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Daryl Ramai
- Department of Internal Medicine, The Brooklyn Hospital Center, Brooklyn, New York, USA
| | - Antonio Facciorusso
- Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Jameel Singh
- Department of Internal Medicine, Mather Hospital, Northwell Health, Port Jefferson, New York, USA
| | - Waqqas Tai
- Department of Internal Medicine, The Brooklyn Hospital Center, Brooklyn, New York, USA
| | - Erika Rijavec
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Barbara Galassi
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Francesco Grossi
- Department of Medicine and Surgery, Medical Oncology Unit, ASST Sette Laghi, Varese, Italy
| | - Alice Indini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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Impact of Body Mass Index on Survival of Metastatic Renal Cancer. J Kidney Cancer VHL 2021; 8:49-54. [PMID: 34414066 PMCID: PMC8336599 DOI: 10.15586/jkcvhl.v8i2.169] [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: 01/23/2021] [Accepted: 07/19/2021] [Indexed: 12/16/2022] Open
Abstract
Obesity has been established as a risk factor for renal cell carcinoma (RCC). Recently, studies have described obesity as a probable protecting factor in the metastatic stage of RCC. In this study, we assessed the relationship between body mass index (BMI) and overall survival in patients under systemic therapy. The correlation between BMI and overall median survival was studied in 76 patients diagnosed with metastatic RCC under systemic therapy. The groups were divided into overweight and obesity (BMI > 25 kg/m2) and underweight or normal (BMI < 25 kg/m2). Statistical analysis was performed using the Cox regression model adjusted by gender. A total of 76 patients were studied: 16 women (21%) and 60 men (79%). The median BMI was 27.96 kg/m2; 24 patients (31.6%) had low BMI and 52 (68.4%) had high BMI. Median overall survival in the group with BMI > 25 kg/m2 was 17 months (95% confidence interval [CI]: 13–34 months), while in the group with BMI ≤ 25 kg/m2, it was 14 months (95% CI: 8–20 months). When adjusted by gender, the group with BMI > 25 kg/m2 presented a hazards ratio of 0.54 (95% CI: 0.30–0.96), P = 0.044 (Log Rank). A high BMI significantly acts as a protecting factor. We observed an increased overall survival of overweight and obese patients within the context of metastatic RCC under systemic treatment. These data confirm the findings published in other studies that suggest the role of lipid metabolism in this type of tumors.
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Nishinaka A, Nakamura S, Tanaka M, Masuda T, Inoue Y, Yamamoto T, Imai T, Hidaka Y, Shimazawa M, Hara H. Excess adiponectin in eyes with progressive ocular vascular diseases. FASEB J 2021; 35:e21313. [PMID: 33484194 DOI: 10.1096/fj.202001740rr] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 12/11/2020] [Accepted: 12/14/2020] [Indexed: 11/11/2022]
Abstract
Anti-vascular endothelial growth factor (VEGF) therapies are now the first-line treatment for many ocular diseases, but some patients are non-responders to these therapies. The purpose of this study was to determine whether the level of adiponectin increased the pathogenesis of retinal edema and neovascularization in the retina of progressive ocular vascular diseases. We examined the role played by adiponectin in two types of cells and animal models which are retinal vein occlusion (RVO) and oxygen-induced retinopathy (OIR) mice. Our results showed that an injection of anti-adiponectin antibody ameliorated the retinal edema and ischemia through the depression of the expression level of VEGF-related factors and tight junction-related proteins in the retina of RVO mice. The intravitreal injection of anti-adiponectin antibody also decreased the degree of retinal neovascularization in an OIR mice. In addition, exposure of human retinal microvascular endothelial cells and human brain microvascular pericytes in culture to adiponectin increased both the vascular permeability and neovascularization through the increase of inflammatory factor and the dropout of the pericytes. These findings indicate that adiponectin plays a critical role in retinal edema and neovascularization, and adiponectin is a potential therapeutic target for the treatment of diabetic macular edema, proliferative diabetic retinopathy, and RVO.
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Affiliation(s)
- Anri Nishinaka
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Shinsuke Nakamura
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Miruto Tanaka
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Tomomi Masuda
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Yuki Inoue
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Takumi Yamamoto
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Takahiko Imai
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Yae Hidaka
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Masamitsu Shimazawa
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
| | - Hideaki Hara
- Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
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Nigro E, Mallardo M, Polito R, Scialò F, Bianco A, Daniele A. Adiponectin and Leptin Exert Antagonizing Effects on HUVEC Tube Formation and Migration Modulating the Expression of CXCL1, VEGF, MMP-2 and MMP-9. Int J Mol Sci 2021; 22:ijms22147516. [PMID: 34299135 PMCID: PMC8307755 DOI: 10.3390/ijms22147516] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/02/2021] [Accepted: 07/12/2021] [Indexed: 12/27/2022] Open
Abstract
Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on viability, migration and tube formation on a human in vitro model, the human umbilical vein endothelial cells (HUVEC) focusing on the expression of the main endothelial angiogenic factors: hypoxia-inducible factor 1-alpha (HIF-1α), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). Treatments with VEGF-A were used as positive control. Our data revealed that, at 24 h treatment, proliferation of HUVEC endothelial cells was not influenced by AdipoRon or leptin administration; after 48 h longer exposure time, the viability was negatively influenced by AdipoRon while leptin treatment and the combination of AdipoRon+leptin produced no effects. In addition, AdipoRon induced a significant increase in complete tubular structures together with induction of cell migration while, on the contrary, leptin did not induce tube formation and inhibited cell migration; interestingly, the co-treatment with both AdipoRon and leptin determined a significant decrease of the tubular structures and cell migration indicating that leptin antagonizes AdipoRon effects. Finally, we found that the effects induced by AdipoRon administration are accompanied by an increase in the expression of CXCL1, VEGF-A, MMP-2 and MMP-9. In conclusion, our data sustain the active role of adiponectin and leptin in linking adipose tissue with the vascular endothelium encouraging the further deepening of the role of adipokines in new vessel’s formation, to candidate them as therapeutic targets.
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Affiliation(s)
- Ersilia Nigro
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy; (E.N.); (M.M.); (R.P.)
- CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy;
| | - Marta Mallardo
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy; (E.N.); (M.M.); (R.P.)
- CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy;
| | - Rita Polito
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy; (E.N.); (M.M.); (R.P.)
- CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy;
| | - Filippo Scialò
- CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy;
- Department of Translational Medical Sciences, Hospital Monaldi, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Andrea Bianco
- Department of Translational Medical Sciences, Hospital Monaldi, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Aurora Daniele
- CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145 Napoli, Italy;
- Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples “Federico II”, 80131 Naples, Italy
- Correspondence: or ; Tel.: +39-0813737856
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Özgöz A, Mutlu Içduygu F, Yükseltürk A, Samli H, Hekimler Öztürk K, Baskan Z, Tütüncü I. Postmenopausal estrogen receptor positive breast cancer and obesity associated gene variants. EXCLI JOURNAL 2021; 20:1133-1144. [PMID: 34345232 PMCID: PMC8326496 DOI: 10.17179/excli2020-2860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 07/02/2021] [Indexed: 11/10/2022]
Abstract
Obesity is one of the most important health risks in postmenopausal women. Molecular pathways that are connected with obesity are believed to interact with the pathogenesis of breast cancer (BC). The aim of this research was to study the polymorphisms of two obesity-associated genes ADIPOQ and FTO that are also related to the pathogenesis of BC. Obesity-associated gene polymorphisms ADIPOQ rs1501299 and rs2241766, and FTO rs1477196, rs7206790, rs8047395, and rs9939609 were studied in 101 Turkish postmenopausal estrogen receptor-positive BC patients and 100 healthy control individuals. ADIPOQ rs1501299 was detected to be associated with protection against BC. The ADIPOQ rs1501299 TT genotype, the rs2241766 GT genotype and the G allele were found to be significantly higher in the control group. In addition, ADIPOQ rs1501299 polymorphism was protective in the recessive model and rs2241766 polymorphism was protective in the dominant model. While none of the FTO gene polymorphisms were found to be associated with BC, the frequencies of rs9939609 A allele and rs7206790 G allele were correlated with body mass index (BMI) in BC patients. ADIPOQ rs1501299 TT genotype, rs2241766 GT genotype, and G allele might be protective against BC in the Turkish population but this conclusion needs to be further verified.
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Affiliation(s)
- Asuman Özgöz
- Kastamonu School of Medicine, Department of Medical Genetics, Kastamonu University, Kastamonu, Turkey
| | - Fadime Mutlu Içduygu
- School of Medicine, Department of Medical Genetics, Giresun University, Giresun, Turkey
| | - Aysegül Yükseltürk
- Fazil Boyner Faculty of Health Sciences, Department of Nutrition and Dietetics, Kastamonu University, Kastamonu, Turkey
| | - Hale Samli
- School of Veterinary Medicine, Department of Genetics, Uludag University, Bursa, Turkey
| | - Kuyas Hekimler Öztürk
- School of Medicine, Department of Medical Genetics, Süleyman Demirel University, Isparta, Turkey
| | - Zuhal Baskan
- Department of Medical Oncology, Acibadem Bursa Hospital, 16110 Bursa, Turkey
| | - Ilknur Tütüncü
- Fazil Boyner Faculty of Health Sciences, Department of Nutrition and Dietetics, Kastamonu University, Kastamonu, Turkey
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Zhao Z, Wu Y, Zhang H, Wang X, Tian X, Wang Y, Qiu Z, Zou L, Tang Z, Huang M. Association of leptin and adiponectin levels with endometriosis: a systematic review and meta-analysis. Gynecol Endocrinol 2021; 37:591-599. [PMID: 33501880 DOI: 10.1080/09513590.2021.1878139] [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] [Indexed: 10/22/2022] Open
Abstract
BACKGROUND We aimed to summarize the available data regarding the levels of leptin and adiponectin and the key modulators of endometriosis compared to the controls. METHODS The electronic databases such as MEDLINE, Embase, Scopus, Cochrane Library, and Web of Science were searched up to October 2020. The circulating and peritoneal levels of leptin and circulating levels of adiponectin were included. We used the Cochrane's Q test and the I2 statistic in this study. These tests' weighted mean difference (WMD) and 95% CIs were considered as the summary effect size. They were then pooled using a random-effects model with the DerSimonian-Laird method. RESULTS Twenty eligible articles (or 25 studies) with 2645 participants (1362 women with endometriosis and 1283 controls) were included. Pooled results showed that women with endometriosis had significantly higher leptin levels (WMD = 4.45 mg/ml, 95%CI = 2.42-6.49, p < .01) and leptin/BMI ratio (WMD = 0.32 mg/ml, 95%CI = 0.23-0.42, p < .001) than the controls, whereas adiponectin levels (WMD = -0.24 mg/ml, 95%CI = -4.27 to -0.01, p = .038) were significantly lower. The pooled results also indicated significantly lower leptin levels in women with advanced-stage endometriosis (WMD = -8.07 mg/ml, 95%CI = -14.22 to -1.92, p = .01) than in the early stage. It was found, however, that there were no significant differences in adiponectin levels of women with advanced-stage endometriosis (WMD = -0.16 mg/ml, 95%CI = -0.64 to 0.32, p = .512) and the early-stage ones. CONCLUSION We showed that leptin levels and leptin/BMI ratio were significantly higher in women with endometriosis than the controls. Nonetheless, patients with endometriosis had significantly lower levels of adiponectin than the controls.
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Affiliation(s)
- Zongquan Zhao
- Department of General Practice, Pingjiang New Town Community Health Service Center, Suzhou, China
| | - Yihong Wu
- Department of General Practice, Runda Community Health Service Center, Suzhou, China
| | - Hao Zhang
- Department of General Practice, Pingjiang New Town Community Health Service Center, Suzhou, China
| | - Xiaohong Wang
- Department of General Practice, Pingjiang New Town Community Health Service Center, Suzhou, China
| | - Xiangfan Tian
- Department of General Practice, Pingjiang New Town Community Health Service Center, Suzhou, China
| | - Yijing Wang
- Community Health Management Center, Suzhou Municipal Hospital, Suzhou, China
| | - Zhenjuan Qiu
- Nursing Department, Pingjiang New Town Community Health Service Center, Suzhou, China
| | - Lingyan Zou
- Department of General Practice, Pingjiang New Town Community Health Service Center, Suzhou, China
| | - Zhenyuan Tang
- Community Health Management Center, Suzhou Municipal Hospital, Suzhou, China
| | - Min Huang
- Department of General Practice, Suzhou Municipal Hospital, Suzhou, China
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Ribatti D, Annese T, Tamma R. Adipocytes, mast cells and angiogenesis. ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY 2021; 61:1051-1056. [PMID: 34171054 PMCID: PMC8343648 DOI: 10.47162/rjme.61.4.07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
Healthy adipose tissue contains a wide variety of innate and adaptive immune cells, including macrophages, dendritic cells, mast cells, eosinophils, neutrophils, and lymphocytes. Numerous signaling molecules in the adipose microenvironment can positively or negatively modulate angiogenic processes, regulate the interaction between the vascular system and adipocytes, and participate in tumor progression. Mast cells are involved in the new formation or metabolism of fat, are present in abundant quantities in fatty tissue, among fat cells, and a number of mediators released from mast cells play a role in adipogenesis. Moreover, mast cells produce several pro-angiogenic factors and are involved in tumor angiogenesis. In this context, the angiogenic effect might be amplified when the adipocytes and mast cells act in concert, and treatment of adipose tissue- and mast cell-associated cancers with anti-angiogenic drugs may represent an alternative or adjuvant strategy for the treatment of these tumors.
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Affiliation(s)
- Domenico Ribatti
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy;
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Jang H, Choi J, Park JK, Won G, Seol JW. Fucoxanthin Exerts Anti-Tumor Activity on Canine Mammary Tumor Cells via Tumor Cell Apoptosis Induction and Angiogenesis Inhibition. Animals (Basel) 2021; 11:1512. [PMID: 34071074 PMCID: PMC8224559 DOI: 10.3390/ani11061512] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 05/12/2021] [Accepted: 05/20/2021] [Indexed: 12/23/2022] Open
Abstract
Fucoxanthin is a carotenoid derived from brown algae. It is known to exhibit anticancer activity, including the promotion of apoptosis and cell cycle arrest in several tumors. However, it remains unclear whether fucoxanthin exhibits anticancer activity against mammary gland tumors. In this study, we evaluated fucoxanthin activity against canine mammary tumor cells (CMT-U27) and human umbilical vein endothelial cells (HUVECs) to investigate its effect on cell viability, migration, tube formation, and angiopoietin 2 (Ang2) expression. Our results showed that fucoxanthin induced apoptosis via caspase activation in CMT-U27 cells. In rat aortic ring assay, fucoxanthin suppressed endothelial cell sprouting. Furthermore, fucoxanthin inhibited tube formation and migration in HUVECs. The number of migrated cells was assessed using CMT-U27 cells. The results demonstrated that fucoxanthin exerted anti-angiogenic activity on HUVECs and CMT-U27 cells by promoting Ang2 expression. In conclusion, our results demonstrated that fucoxanthin induced tumor cell death and inhibited angiogenesis, suggesting that fucoxanthin could be considered as a promising therapeutic agent for canine mammary gland tumors.
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Affiliation(s)
| | | | | | - Gayeon Won
- College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Jeollabuk-do, Korea; (H.J.); (J.C.); (J.-K.P.)
| | - Jae-Won Seol
- College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Jeollabuk-do, Korea; (H.J.); (J.C.); (J.-K.P.)
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Suneja S, Gangopadhyay S, Saini V, Dawar R, Kaur C. Emerging Diabetic Novel Biomarkers of the 21st Century. ANNALS OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES (INDIA) 2021. [DOI: 10.1055/s-0041-1726613] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
AbstractDiabetes is a growing epidemic with estimated prevalence of infected to reach ~592 million by the year 2035. An effective way to approach is to detect the disease at a very early stage to reduce the complications and improve lifestyle management. Although several traditional biomarkers including glucated hemoglobin, glucated albumin, fructosamine, and 1,5-anhydroglucitol have helped in ease of diagnosis, there is lack of sensitivity and specificity and are inaccurate in certain clinical settings. Thus, search for new and effective biomarkers is a continuous process with an aim of accurate and timely diagnosis. Several novel biomarkers have surged in the present century that are helpful in timely detection of the disease condition. Although it is accepted that a single biomarker will have its inherent limitations, combining several markers will help to identify individuals at high risk of developing prediabetes and eventually its progression to frank diabetes. This review describes the novel biomarkers of the 21st century, both in type 1 and type 2 diabetes mellitus, and their present potential for assessing risk stratification due to insulin resistance that will pave the way for improved clinical outcome.
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Affiliation(s)
- Shilpa Suneja
- Department of Biochemistry, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
| | - Sukanya Gangopadhyay
- Department of Biochemistry, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
| | - Vandana Saini
- Department of Biochemistry, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
| | - Rajni Dawar
- Department of Biochemistry, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
| | - Charanjeet Kaur
- Department of Biochemistry, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
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Visceral-to-subcutaneous fat ratio independently predicts the prognosis of locally advanced gastric cancer----- highlighting the role of adiponectin receptors and PPARα, β/ δ, ɤ. Eur J Surg Oncol 2021; 47:3064-3073. [PMID: 33941417 DOI: 10.1016/j.ejso.2021.04.028] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/23/2021] [Accepted: 04/20/2021] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Results of computed tomography body composition (CTBC) predicting long-term outcomes of gastric cancer have been mixed and the plausible mechanism remains elusive. METHODS We retrospectively enrolled a cohort of stage III gastric cancer who had undergone curative-intent gastrectomy. Clinicopathological variables, preoperative CTBC including abdominal muscle, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), and nutritional and inflammatory index were taken together to construct prognostic analysis. In vitro tests using co-culture system of gastric cancer cell lines and visceral adipocytes were conducted. RESULTS A total of 191 eligible patients were enrolled. By multivariate analysis, SAT and VAT/ SAT ratio were prognostic factors of disease-free survival, while sarcopenia was not. SAT remained as a prognostic factor of overall survival. SAT index was positively correlated with prognostic nutritional index, while VAT HU was positively correlated with platelet-to-lymphocyte ratio. Expression of adiponectin receptor 1 and 2 (AdipoR1, R2), and peroxisome proliferator-activated receptor (PPAR) α, β/δ, ɤ of patients with higher VAT/SAT ratio were decreased as compared to those with lower VAT/SAT ratio. Proliferation of gastric cancer cells co-cultured with adipocytes was increased by 50-100% and accompanied by down-regulation of mRNAs of AdipoR1, 2, PPARα, β/δ, ɤ, and pro-apoptotic genes, as compared to their controls. CONCLUSION SAT and VAT played exactly opposite prognostic roles of locally advanced gastric cancers, which might work through modulation of AdipoR1, 2 and PPARα, β/δ, ɤ. Preoperative CTBC, supplementary to classic TNM system, helps clinicians tailor individualized adjuvant therapy and/or nutritional support.
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Hammel JH, Bellas E. Endothelial cell crosstalk improves browning but hinders white adipocyte maturation in 3D engineered adipose tissue. Integr Biol (Camb) 2021; 12:81-89. [PMID: 32219324 DOI: 10.1093/intbio/zyaa006] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 02/07/2020] [Accepted: 02/21/2020] [Indexed: 12/13/2022]
Abstract
Central to the development of adipose tissue (AT) engineered models is the supporting vasculature. It is a key part of AT function and long-term maintenance, but the crosstalk between adipocytes and endothelial cells is not well understood. Here, we directly co-culture the two cell types at varying ratios in a 3D Type I collagen gel. Constructs were evaluated for adipocyte maturation and function and vascular network organization. Further, these constructs were treated with forskolin, a beta-adrenergic agonist, to stimulate lipolysis and browning. Adipocytes in co-cultures were found to be less mature than an adipocyte-only control, shown by smaller lipid droplets and downregulation of key adipocyte-related genes. The most extensive vascular network formation was found in the 1:1 co-culture, supported by vascular endothelial growth factor (VEGF) upregulation. After forskolin treatment, the presence of endothelial cells was shown to upregulate PPAR coactivator 1 alpha (PGC-1α) and leptin, but not uncoupling protein 1 (UCP1), suggesting a specific crosstalk that enhances early stages of browning.
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Affiliation(s)
- Jennifer H Hammel
- Department of Bioengineering, Temple University, Philadelphia, PA, USA
| | - Evangelia Bellas
- Department of Bioengineering, Temple University, Philadelphia, PA, USA
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