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Fu X, Zhao Y, Wu Y, Wen L, Huo W, Zhang D, Zhang Y, Li J, Lu X, Hu F, Zhang M, Hu D. Relationship between trajectory of Chinese visceral adiposity index and risk of type 2 diabetes mellitus: Evidence from the China-PAR project. Diabetes Obes Metab 2025; 27:785-794. [PMID: 39562295 DOI: 10.1111/dom.16074] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 10/28/2024] [Accepted: 11/05/2024] [Indexed: 11/21/2024]
Abstract
AIMS This study aimed to identify the distinct change trajectories of the Chinese visceral adiposity index (CVAI) over time and to investigate their associations with risk of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS This study included 52 394 participants from the prospective project, the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). The CVAI was calculated using measures of age, body mass index, waist circumference, triglycerides and high-density lipoprotein cholesterol. Latent mixture modelling was conducted to fit distinct trajectory patterns. The logistic regression model was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of T2DM with various CVAI trajectory patterns. RESULTS Four distinct CVAI trajectory patterns were identified: low-increasing, moderate-increasing, moderate high-increasing and high-increasing. Compared with low-increasing CVAI, participants with moderate-increasing (OR 1.73, 95% CI 1.49-2.00), moderate high-increasing (3.48, 3.01-4.03) and high-increasing CVAI (5.50, 4.67-6.47) had a significantly increased risk of T2DM. Similar trajectory patterns were identified in both men and women. The ORs (95% CI) for moderate-increasing, moderate high-increasing and high-increasing groups were 3.28 (2.56-4.19), 7.85 (6.09-10.13) and 13.21 (9.98-17.49) in women respectively, and 1.20 (0.99-1.45), 2.18 (1.82-2.62) and 3.60 (2.93-4.43) in men respectively, when compared to the low-increasing CVAI group. Further, significant effect modifications for age, smoking and physical activity (all Pinteraction <0.05) were observed in the relationship between CVAI trajectory patterns and T2DM. CONCLUSIONS Initially high and persistently elevated CVAI is significantly associated with an increased risk of T2DM, with a particular focus on women, younger people, nonsmokers and physically inactive individuals. Continuous monitoring of CVAI levels will benefit effective identification, early intervention and management of individuals at high risk of T2DM.
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Affiliation(s)
- Xueru Fu
- Department of Cardiovascular Medicine, The Seventh People's Hospital of Zhengzhou, Zhengzhou, China
- Henan Provincial Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou, China
| | - Yang Zhao
- Department of General Practice, The Affiliated Luohu Hospital of Shenzhen University Medical School, Shenzhen, China
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Yuying Wu
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Liuding Wen
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Weifeng Huo
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Dongdong Zhang
- Department of General Practice, The Affiliated Luohu Hospital of Shenzhen University Medical School, Shenzhen, China
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Yanyan Zhang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Key Laboratory of Cardiovascular Epidemiology, Chinese Academy of Medical Sciences, Beijing, China
- Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianxin Li
- Key Laboratory of Cardiovascular Epidemiology, Chinese Academy of Medical Sciences, Beijing, China
- Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiangfeng Lu
- Key Laboratory of Cardiovascular Epidemiology, Chinese Academy of Medical Sciences, Beijing, China
- Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fulan Hu
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen, China
| | - Ming Zhang
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen, China
| | - Dongsheng Hu
- Department of Cardiovascular Medicine, The Seventh People's Hospital of Zhengzhou, Zhengzhou, China
- Henan Provincial Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou, China
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Kuai D, Tang Q, Wang X, Yan Q, Tian W, Zhang H. Relationship between serum apelin, visfatin levels, and body composition in Polycystic Ovary Syndrome patients. Eur J Obstet Gynecol Reprod Biol 2024; 297:24-29. [PMID: 38555852 DOI: 10.1016/j.ejogrb.2024.03.034] [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: 01/16/2024] [Revised: 03/08/2024] [Accepted: 03/26/2024] [Indexed: 04/02/2024]
Abstract
OBJECTIVE To investigate the relationship between body composition and serum visfatin and apelin levels in patients with polycystic ovary syndrome (PCOS). METHODS In this prospective observational study, the differences in body composition, levels of gonadal hormone concentrations, glucose metabolism, apelin, and visfatin were compared between PCOS patients and the control group. PCOS patients were further divided into different subgroups according to different obesity criteria and the differences between serum visfatin and apelin levels in different subgroups were compared. Finally, the correlation of serum visfatin levels and apelin levels with body composition, and metabolism-related indicators in PCOS patients was explored. RESULTS A total collected 178 cases of PCOS patients and 172 cases of healthy women (control group) between 2020 July and 2021 November. In PCOS patients, their weight, Body Mass Index (BMI), Waist Hip Rate (WHR), Fat-Free Mass Index (FFMI), Percent Body Fat (PBF), Fat mass index (FMI), PBF of Arm, PBF of Leg, PBF of the Trunk, Visceral Fat Level (VFL), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Luteinizing hormone (LH) were significantly higher than in the control group (all P < 0.001), Percent Skeletal Muscle (PSM), PSM of Leg, and PSM of the Trunk were significantly decreased than in the control group (all P < 0.001). The PCOS patients had significantly higher serum visfatin levels and apelin levels compared with the control group (all P < 0.001). In PBF > 35 % PCOS patients, the apelin and visfatin levels were significantly higher than the PBF ≤ 35 % PCOS patients. In WHR ≥ 0.85 and BMI ≥ 24 kg/m2 PCOS patients, the visfatin levels were significantly higher than the WHR < 0.85 and BMI < 24 kg/m2 PCOS patients. Serum apelin and visfatin positively correlated with BMI level, WHR, FFMI, PBF, FMI, PBF of arms, PBF of legs, PBF of the trunk, VFL, FBG, HOMA-IR index and negatively correlated with PSM, PSM of legs, and PSM of the trunk (all P < 0.001). CONCLUSIONS Compared with healthy women, Patients with PCOS have an increased fat content in various parts of the body, reduced skeletal muscle content, and are often complicated by metabolic abnormalities. Serum visfatin and apelin correlated not only with obesity, fat mass, and fat distribution but also with muscle mass and distribution. It may be possible to reduce the long-term risk of metabolic disease in PCOS through the monitoring and management of the body composition in PCOS patients or to reflect the therapeutic effect of PCOS.
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Affiliation(s)
- Dan Kuai
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Qingtao Tang
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xiang Wang
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Qi Yan
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Wenyan Tian
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Huiying Zhang
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin 300052, China.
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George BT, Jhancy M, Dube R, Kar SS, Annamma LM. The Molecular Basis of Male Infertility in Obesity: A Literature Review. Int J Mol Sci 2023; 25:179. [PMID: 38203349 PMCID: PMC10779000 DOI: 10.3390/ijms25010179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 12/12/2023] [Accepted: 12/20/2023] [Indexed: 01/12/2024] Open
Abstract
The rising incidence of obesity has coincided with rising levels of poor reproductive outcomes. The molecular basis for the association of infertility in obese males is now being explained through various mechanisms. Insulin resistance, hyperglycemia, and changes in serum and gonadal concentrations of adipokines, like leptin, adiponectin, resistin, and ghrelin have been implicated as causes of male infertility in obese males. The effects of obesity and hypogonadism form a vicious cycle whereby dysregulation of the hypothalamic-pituitary-testicular axis-due to the effect of the release of multiple mediators, thus decreasing GnRH release from the hypothalamus-causes decreases in LH and FSH levels. This leads to lower levels of testosterone, which further increases adiposity because of increased lipogenesis. Cytokines such as TNF-α and interleukins, sirtuins, and other inflammatory mediators like reactive oxygen species are known to affect fertility in obese male adults. There is evidence that parental obesity can be transferred through subsequent generations to offspring through epigenetic marks. Thus, negative expressions like obesity and infertility have been linked to epigenetic marks being altered in previous generations. The interesting aspect is that these epigenetic expressions can be reverted by removing the triggering factors. These positive modifications are also transmitted to subsequent generations.
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Affiliation(s)
- Biji Thomas George
- Department of Surgery, RAK College of Medical Sciences, RAKMHSU, Ras al Khaimah P.O. Box 11172, United Arab Emirates
| | - Malay Jhancy
- Department of Pediatrics, RAK College of Medical Sciences, RAKMHSU, Ras al Khaimah P.O. Box 11172, United Arab Emirates; (M.J.); (S.S.K.)
| | - Rajani Dube
- Department of Obstetrics and Gynecology, RAK College of Medical Sciences, RAKMHSU, Ras al Khaimah P.O. Box 11172, United Arab Emirates;
| | - Subhranshu Sekhar Kar
- Department of Pediatrics, RAK College of Medical Sciences, RAKMHSU, Ras al Khaimah P.O. Box 11172, United Arab Emirates; (M.J.); (S.S.K.)
| | - Lovely Muthiah Annamma
- Department of Clinical Sciences, Ajman University, Ajman P.O. Box 346, United Arab Emirates;
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Pelczyńska M, Miller-Kasprzak E, Piątkowski M, Mazurek R, Klause M, Suchecka A, Bucoń M, Bogdański P. The Role of Adipokines and Myokines in the Pathogenesis of Different Obesity Phenotypes-New Perspectives. Antioxidants (Basel) 2023; 12:2046. [PMID: 38136166 PMCID: PMC10740719 DOI: 10.3390/antiox12122046] [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: 10/30/2023] [Revised: 11/19/2023] [Accepted: 11/25/2023] [Indexed: 12/24/2023] Open
Abstract
Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes: normal-weight obesity (NWO), metabolically obese normal-weight (MONW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). A range of pathophysiological mechanisms underlie the occurrence of obesity, including inflammation, oxidative stress, adipokine secretion, and other processes related to the pathophysiology of adipose tissue (AT). Body mass index (BMI) is the key indicator in the diagnosis of obesity; however, in the case of the NWO and MONW phenotypes, the metabolic disturbances are present despite BMI being within the normal range. On the other hand, MHO subjects with elevated BMI values do not present metabolic abnormalities. The MUO phenotype involves both a high BMI value and an abnormal metabolic profile. In this regard, attention has been focused on the variety of molecules produced by AT and their role in the development of obesity. Nesfatin-1, neuregulin 4, myonectin, irisin, and brain-derived neurotrophic factor (BDNF) all seem to have protective effects against obesity. The primary mechanism underlying the action of nesfatin-1 involves an increase in insulin sensitivity and reduced food intake. Neuregulin 4 sup-presses lipogenesis, decreases lipid accumulation, and reduces chronic low-grade inflammation. Myonectin lowers the amount of fatty acids in the bloodstream by increasing their absorption in the liver and AT. Irisin stimulates the browning of white adipose tissue (WAT) and consequently in-creases energy expenditure, additionally regulating glucose metabolism. Another molecule, BDNF, has anorexigenic effects. Decorin protects against the development of hyperglycemia, but may also contribute to proinflammatory processes. Similar effects are shown in the case of visfatin and chemerin, which may predispose to obesity. Visfatin increases adipogenesis, causes cholesterol accumulation in macrophages, and contributes to the development of glucose intolerance. Chemerin induces angiogenesis, which promotes the expansion of AT. This review aims to discuss the role of adipokines and myokines in the pathogenesis of the different obesity phenotypes.
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Affiliation(s)
- Marta Pelczyńska
- Chair and Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poznań, Poland; (E.M.-K.); (P.B.)
| | - Ewa Miller-Kasprzak
- Chair and Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poznań, Poland; (E.M.-K.); (P.B.)
| | - Marcin Piątkowski
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland
| | - Roksana Mazurek
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland
| | - Mateusz Klause
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland
| | - Anna Suchecka
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland
| | - Magdalena Bucoń
- Faculty of Medicine, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland
| | - Paweł Bogdański
- Chair and Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569 Poznań, Poland; (E.M.-K.); (P.B.)
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Tarfeen N, Nisa KU, Ahmad MB, Waza AA, Ganai BA. Metabolic and Genetic Association of Vitamin D with Calcium Signaling and Insulin Resistance. Indian J Clin Biochem 2023; 38:407-417. [PMID: 37746541 PMCID: PMC10516840 DOI: 10.1007/s12291-022-01105-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 11/29/2022] [Indexed: 12/14/2022]
Abstract
Various evidences have unveiled the significance of Vitamin D in diverse processes which include its action in prevention of immune dysfunction, cancer and cardiometabolic disorders. Studies have confirmed the function of VD in controlling the expression of approximately nine hundred genes including gene expression of insulin. VD insufficiency may be linked with the pathogenesis of diseases that are associated with insulin resistance (IR) including diabetes as well as obesity. Thus, VD lowers IR-related disorders such as inflammation and oxidative stress. This review provides an insight regarding the molecular mechanism manifesting, how insufficiency of VD may be connected with the IR and diabetes. It also discusses the effect of VD in maintaining the Ca2+ levels in beta cells of the pancreas and in the tissues that are responsive to insulin.
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Affiliation(s)
- Najeebul Tarfeen
- Centre of Research for Development, University of Kashmir, Srinagar, India
| | - Khair Ul Nisa
- Department of Environmental Science, University of Kashmir, Srinagar, India
| | - Mir Bilal Ahmad
- Department of Biochemistry, University of Kashmir, Srinagar, India
| | - Ajaz Ahmad Waza
- Multidisciplinary Research Unit (MRU), Government Medical Collage (GMC) Srinagar, Srinagar, J & K 190010 India
| | - Bashir Ahmad Ganai
- Centre of Research for Development, University of Kashmir, Srinagar, India
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Chen TH, Hsu HC, You JF, Lai CC, Tsou YK, Hsu CL, Fann CSJ, Chien RN, Chang ML. Extracellular Nicotinamide Phosphoribosyltransferase as a Surrogate Marker of Prominent Malignant Potential in Colonic Polyps: A 2-Year Prospective Study. Cancers (Basel) 2023; 15:1702. [PMID: 36980589 PMCID: PMC10046025 DOI: 10.3390/cancers15061702] [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: 01/06/2023] [Revised: 03/03/2023] [Accepted: 03/08/2023] [Indexed: 03/14/2023] Open
Abstract
BACKGROUND/AIMS The implications of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a cancer metabokine, in colonic polyps remain uncertain. METHODS A 2-year prospective cohort study of patients who underwent colonoscopy was conducted. Biochemical parameters and serum eNAMPT levels were analyzed at baseline and every 24 weeks postpolypectomy. NAMPT-associated single-nucleotide polymorphisms (SNPs), including rs61330082, rs2302559, rs10953502, and rs23058539, were assayed. RESULTS Of 532 patients, 80 (15%) had prominent malignant potential (PMP) in colonic polyps, including villous adenomas (n = 18, 3.3%), adenomas with high-grade dysplasia (n = 33, 6.2%), and adenocarcinomas (n = 29, 5.5%). Baseline associations were as follows: colonic polyp pathology (p < 0.001), total cholesterol (p = 0.019), and neutrophil-to-lymphocyte ratio (p = 0.023) with eNAMPT levels; and age (p < 0.001), polyp size (p < 0.001), and eNAMPT levels (p < 0.001) with polyp pathology. Higher baseline eNAMPT levels were noted in patients harboring polyps with PMP than in patients without PMP (p < 0.001), and baseline eNAMPT levels significantly predicted PMP (cutoff: >4.238 ng/mL, p < 0.001). Proportions of eNAMPT-positive glandular and stromal cells were higher in polyps with PMP than in polyps without PMP (64.55 ± 11.94 vs. 14.82 ± 11.45%, p = 0.025). eNAMPT levels decreased within 48 weeks postpolypectomy (p = 0.01) and remained stable afterward regardless of PMP until 96 weeks postpolypectomy. However, those with PMP had a higher degree of eNAMPT decline within 24 weeks (p = 0.046). All investigated SNPs were in linkage disequilibrium with each other but were not associated with eNAMPT levels. CONCLUSION With a link to inflammation and lipid metabolism, along with its decreasing trend after polypectomy, serum eNAMPT may serve as a surrogate marker of PMP in colonic polyps. In situ probing of the NAMPT-associated pathway holds promise in attenuating PMP, as much of the eNAMPT likely originates from colonic polyps.
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Affiliation(s)
- Tsung-Hsing Chen
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
| | - Hung-Chih Hsu
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
- Division of Hematology-Oncology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Jeng-Fu You
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
- Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Cheng-Chou Lai
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
- Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Yung-Kuan Tsou
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
| | - Chia-Lin Hsu
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Cathy S. J. Fann
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
| | - Ming-Ling Chang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
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Adipokines as Regulators of Autophagy in Obesity-Linked Cancer. Cells 2022; 11:cells11203230. [PMID: 36291097 PMCID: PMC9600294 DOI: 10.3390/cells11203230] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 10/02/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022] Open
Abstract
Excess body weight and obesity have become significant risk factors for cancer development. During obesity, adipose tissue alters its biological function, deregulating the secretion of bioactive factors such as hormones, cytokines, and adipokines that promote an inflammatory microenvironment conducive to carcinogenesis and tumor progression. Adipokines regulate tumor processes such as apoptosis, proliferation, migration, angiogenesis, and invasion. Additionally, it has been found that they can modulate autophagy, a process implicated in tumor suppression in healthy tissue and cancer progression in established tumors. Since the tumor-promoting role of autophagy has been well described, the process has been suggested as a therapeutic target in cancer. However, the effects of targeting autophagy might depend on the tumor type and microenvironmental conditions, where circulating adipokines could influence the role of autophagy in cancer. Here, we review recent evidence related to the role of adipokines in cancer cell autophagy in an effort to understand the tumor response in the context of obesity under the assumption of an autophagy-targeting treatment.
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Exposure to nanographene oxide induces gene expression dysregulation in normal human astrocytes. Endocr Regul 2022; 56:216-226. [DOI: 10.2478/enr-2022-0023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Objective. Nanographene oxide, an oxidation derivative of graphene, is considered to be one of the nanomaterials attractive for biomedical applications, although this nanomaterial is toxic. The increasing exploitation of graphene-based materials necessitates a comprehensive evaluation of the potential impact of these materials on the human health. Moreover, it is necessary to investigate in detail the mechanisms of its toxic effect on living cells particularly at the genome level. The present study aimed to evaluate the impact of low doses of nanographene oxide on the expression of key regulatory genes in normal human astrocytes.
Methods. Normal human astrocytes, line NHA/TS, were exposed to low doses of nanographene oxide (1 and 4 ng/ml) for 24 h. RNA was extracted from the cells and used for cDNA synthesis. The expression levels of NAMPT, TSPAN13, BCAR3, BRCA1, PTGS2, P4HA1, and P4HA2 mRNAs as well as microRNAs were measured by quantitative polymerase chain reaction.
Results. It was found that the low doses of nanographene oxide induced a dysregulation in the expression of the key regulatory genes in normal human astrocytes in dose-dependent (1 and 4 ng/ml) and gene-specific manner. Nanographene oxide also strongly suppressed the expression of NAMPT, BCAR3, and TSPAN13 genes and significantly up-regulated BRCA1, PTGS2, P4HA1, and P4HA2 ones with a more significant effect in P4HA1 and P4HA2 genes. The expression of miR-96-5p and miR-145-5p was also down-regulated in astrocytes treated with nanographene oxide in a dose-dependent manner.
Conclusion. The data obtained demonstrate that the low doses of nanographene oxide disturbed the genome functions by changing the expression levels of key regulatory genes in gene-specific and dose-dependent manner. Moreover, a higher dose of nanographene oxide induced more pronounced changes in expression of genes indicating for both genotoxic and neurotoxic possible effects in the normal human astrocytes.
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Suau R, Pardina E, Domènech E, Lorén V, Manyé J. The Complex Relationship Between Microbiota, Immune Response and Creeping Fat in Crohn's Disease. J Crohns Colitis 2022; 16:472-489. [PMID: 34528668 DOI: 10.1093/ecco-jcc/jjab159] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In the last decade, there has been growing interest in the pathological involvement of hypertrophic mesenteric fat attached to the serosa of the inflamed intestinal segments involved in Crohn's disease [CD], known as creeping fat. In spite of its protective nature, creeping fat harbours an aberrant inflammatory activity which, in an already inflamed intestine, may explain why creeping fat is associated with a greater severity of CD. The transmural inflammation of CD facilitates the interaction of mesenteric fat with translocated intestinal microorganisms, contributing to activation of the immune response. This may be not the only way in which microorganisms alter the homeostasis of this fatty tissue: intestinal dysbiosis may also impair xenobiotic metabolism. All these CD-related alterations have a functional impact on nuclear receptors such as the farnesoid X receptor or the peroxisome proliferator-activated receptor γ, which are implicated in regulation of the immune response, adipogenesis and the maintenance of barrier function, as well as on creeping fat production of inflammatory-associated cells such as adipokines. The dysfunction of creeping fat worsens the inflammatory course of CD and may favour intestinal fibrosis and fistulizing complications. However, our current knowledge of the pathophysiology and pathogenic role of creeping fat is controversial and a better understanding might provide new therapeutic targets for CD. Here we aim to review and update the key cellular and molecular alterations involved in this inflammatory process that link the pathological components of CD with the development of creeping fat.
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Affiliation(s)
- Roger Suau
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| | - Eva Pardina
- Biochemistry and Molecular Biomedicine Department, University of Barcelona, Barcelona (Catalonia), Spain
| | - Eugeni Domènech
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain.,Gastroenterology Department, 'Germans Trias i Pujol' University Hospital, Badalona (Catalonia), Spain
| | - Violeta Lorén
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| | - Josep Manyé
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
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Molecular Mechanisms Underlying the Relationship between Obesity and Male Infertility. Metabolites 2021; 11:metabo11120840. [PMID: 34940598 PMCID: PMC8706114 DOI: 10.3390/metabo11120840] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/01/2021] [Accepted: 12/02/2021] [Indexed: 01/29/2023] Open
Abstract
In recent decades, the worldwide prevalence of obesity has risen dramatically and is currently estimated to be around 20%. Obesity is linked to an increased risk of comorbidities and premature mortality. Several studies have shown that obesity negatively impacts male fertility through various mechanisms. This review aims to investigate the molecular mechanisms through which obesity impairs male reproduction, including obesity-associated hypogonadism and its effects on spermatogenesis, chronic inflammation, and oxidative stress. Obesity negatively impacts both conventional and biofunctional sperm parameters, and it also induces epigenetic changes that can be transferred to offspring. Moreover, obesity-related diseases are linked to a dysregulation of adipocyte function and micro-environmental inflammatory processes. The dysregulated adipokines significantly influence insulin signaling, and they may also have a detrimental effect on testicular function. Sirtuins can also play an important role in inflammatory and metabolic responses in obese patients. Understanding the molecular mechanisms that are involved in obesity-induced male infertility could increase our ability to identify novel targets for the prevention and treatment of obesity and its related consequences.
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Qie R, Li Q, Zhao Y, Han M, Liu D, Guo C, Zhou Q, Tian G, Huang S, Wu X, Zhang Y, Qin P, Li H, Wang J, Cheng R, Lin J, Sun X, Wu Y, Li Y, Yang X, Zhao Y, Feng Y, Zhang M, Hu D. Association of hypertriglyceridemic waist-to-height ratio and its dynamic status with risk of type 2 diabetes mellitus: The Rural Chinese Cohort Study. Diabetes Res Clin Pract 2021; 179:108997. [PMID: 34371063 DOI: 10.1016/j.diabres.2021.108997] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 05/25/2021] [Accepted: 08/04/2021] [Indexed: 11/29/2022]
Abstract
AIMS To evaluate the risk of type 2 diabetes mellitus (T2DM) in a prospective study with hypertriglyceridemic waist-to-height ratio (HWHtR) and its dynamic status. METHODS We collected data for 12,248 participants ≥18 years in this study. Cox's proportional-hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM risk by baseline HWHtR. Multiple logistic regression analysis was used to estimate odds ratios (ORs) and 95% CIs for T2DM risk by transformation in HWHtR. RESULTS We identified 839 T2DM cases during a median follow-up of 5.92 years. Compared with normal TG level and normal WHtR, T2DM risk was increased with high TG level and high WHtR (aHR 2.04, 95% CI 1.49-2.79). Similar results were observed in subgroup analyses by sex and age. During follow-up, T2DM risk was increased with stable high TG level and high WHtR (aOR 4.45, 95% CI 2.76-7.17) compared with stable normal TG level and normal WHtR. The results above were robust in sensitivity analyses. CONCLUSIONS HWHtR phenotype and its dynamic status were associated with risk of T2DM. Our study suggests that primary prevention and avoiding the appearance of the HWHtR phenotype in the rural Chinese population may reduce the T2DM risk.
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Affiliation(s)
- Ranran Qie
- Department of Endocrinology, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, PR China.; Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Quanman Li
- Department of Endocrinology, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, PR China.; Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yang Zhao
- Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Minghui Han
- Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Dechen Liu
- Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Chunmei Guo
- Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Qionggui Zhou
- School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Gang Tian
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Shengbing Huang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Xiaoyan Wu
- School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yanyan Zhang
- School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Pei Qin
- School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Honghui Li
- Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Jian Wang
- Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Ruirong Cheng
- Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Jinchun Lin
- Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Xizhuo Sun
- Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yuying Wu
- School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Yang Li
- School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Xingjin Yang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Yang Zhao
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Yifei Feng
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Ming Zhang
- School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China
| | - Dongsheng Hu
- Department of Endocrinology, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, PR China.; Study Team of Shenzhen's Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China.
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Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer's Disease. Int J Mol Sci 2021; 22:ijms22115603. [PMID: 34070553 PMCID: PMC8198882 DOI: 10.3390/ijms22115603] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/16/2021] [Accepted: 05/21/2021] [Indexed: 02/07/2023] Open
Abstract
Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia. Metabolic disorders including obesity and type 2 diabetes mellitus (T2DM) may stimulate amyloid β (Aβ) aggregate formation. AD, obesity, and T2DM share similar features such as chronic inflammation, increased oxidative stress, insulin resistance, and impaired energy metabolism. Adiposity is associated with the pro-inflammatory phenotype. Adiposity-related inflammatory factors lead to the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of the pro-inflammatory cytokines including interleukin-1β (IL-1β) and interleukin-18 (IL-18). Activation of the inflammasome complex, particularly NLRP3, has a crucial role in obesity-induced inflammation, insulin resistance, and T2DM. The abnormal activation of the NLRP3 signaling pathway influences neuroinflammatory processes. NLRP3/IL-1β signaling could underlie the association between adiposity and cognitive impairment in humans. The review includes a broadened approach to the role of obesity-related diseases (obesity, low-grade chronic inflammation, type 2 diabetes, insulin resistance, and enhanced NLRP3 activity) in AD. Moreover, we also discuss the mechanisms by which the NLRP3 activation potentially links inflammation, peripheral and central insulin resistance, and metabolic changes with AD.
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13
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Karaskova E, Velganova-Veghova M, Geryk M, Foltenova H, Kucerova V, Karasek D. Role of Adipose Tissue in Inflammatory Bowel Disease. Int J Mol Sci 2021; 22:4226. [PMID: 33921758 PMCID: PMC8073530 DOI: 10.3390/ijms22084226] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/05/2021] [Accepted: 04/16/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBDs), chronic inflammatory disorders affecting the gastrointestinal tract, include Crohn's disease and ulcerative colitis. There are increasing clinical and experimental data showing that obesity, especially visceral adiposity, plays a substantial role in the pathogenesis of IBD. Obesity seems to be an important risk factor also for IBD disease severity and clinical outcomes. Visceral adipose tissue is an active multifunctional metabolic organ involved in lipid storage and immunological and endocrine activity. Bowel inflammation penetrates the surrounding adipose tissue along the mesentery. Mesenteric fat serves as a barrier to inflammation and controls immune responses to the translocation of gut bacteria. At the same time, mesenteric adipose tissue may be the principal source of cytokines and adipokines responsible for inflammatory processes associated with IBD. This review is particularly focusing on the potential role of adipokines in IBD pathogenesis and their possible use as promising therapeutic targets.
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Affiliation(s)
- Eva Karaskova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Maria Velganova-Veghova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Milos Geryk
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Hana Foltenova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Veronika Kucerova
- Department of Clinical Biochemistry, University Hospital Olomouc, 77900 Olomouc, Czech Republic;
| | - David Karasek
- Third Department of Internal Medicine—Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic;
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The Influence of Biologically Active Substances Secreted by the Adipose Tissue on Endometrial Cancer. Diagnostics (Basel) 2021; 11:diagnostics11030494. [PMID: 33799622 PMCID: PMC8000529 DOI: 10.3390/diagnostics11030494] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 03/07/2021] [Accepted: 03/08/2021] [Indexed: 12/24/2022] Open
Abstract
Endometrial cancer is one of the most frequently diagnosed gynecological neoplasms in developed countries and its incidence is rising. Usually, it is diagnosed in the early stages of the disease and has a good prognosis; however, in later stages, the rate of recurrence reaches up to 60%. The discrepancy in relapse rates is due to the heterogeneity of the group related to the presence of prognostic factors affecting survival parameters. Increased body weight, diabetes, metabolic disturbances and estrogen imbalance are important factors for the pathogenesis of endometrial cancer. Even though prognostic factors such as histopathological grade, clinical stage, histological type and the presence of estrogen and progesterone receptors are well known in endometrial cancer, the search for novel prognostic biomarkers continues. Adipose tissue is an endocrine organ involved in metabolism, immune response and the production of biologically active substances participating in cell growth and differentiation, angiogenesis, apoptosis and carcinogenesis. In this manuscript, we review the impact of factors secreted by the adipose tissue involved in the regulation of glucose and lipid metabolism (leptin, adiponectin, omentin, vaspin, galectins) and factors responsible for homeostasis maintenance, inflammatory processes, angiogenesis and oxidative stress (IL-1β, 6, 8, TNFα, Vascular endothelial growth factor (VEGF), Fibroblast growth factors (FGFs)) in the diagnosis and prognosis of endometrial cancer.
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15
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Heyde I, Begemann K, Oster H. Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism. Endocrinology 2021; 162:6102571. [PMID: 33453099 PMCID: PMC7864004 DOI: 10.1210/endocr/bqab009] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Indexed: 12/17/2022]
Abstract
The term energy metabolism comprises the entirety of chemical processes associated with uptake, conversion, storage, and breakdown of nutrients. All these must be tightly regulated in time and space to ensure metabolic homeostasis in an environment characterized by cycles such as the succession of day and night. Most organisms evolved endogenous circadian clocks to achieve this goal. In mammals, a ubiquitous network of cellular clocks is coordinated by a pacemaker residing in the hypothalamic suprachiasmatic nucleus. Adipocytes harbor their own circadian clocks, and large aspects of adipose physiology are regulated in a circadian manner through transcriptional regulation of clock-controlled genes. White adipose tissue (WAT) stores energy in the form of triglycerides at times of high energy levels that then serve as fuel in times of need. It also functions as an endocrine organ, releasing factors in a circadian manner to regulate food intake and energy turnover in other tissues. Brown adipose tissue (BAT) produces heat through nonshivering thermogenesis, a process also controlled by the circadian clock. We here review how WAT and BAT contribute to the circadian regulation of energy metabolism. We describe how adipose rhythms are regulated by the interplay of systemic signals and local clocks and summarize how adipose-originating circadian factors feed-back on metabolic homeostasis. The role of adipose tissue in the circadian control of metabolism becomes increasingly clear as circadian disruption leads to alterations in adipose tissue regulation, promoting obesity and its sequelae. Stabilizing adipose tissue rhythms, in turn, may help to combat disrupted energy homeostasis and obesity.
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Affiliation(s)
- Isabel Heyde
- Institute of Neurobiology, University of Lübeck, Lübeck, Germany
| | | | - Henrik Oster
- Institute of Neurobiology, University of Lübeck, Lübeck, Germany
- Correspondence: Henrik Oster, PhD, Institute of Neurobiology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.
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16
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Rajesh Y, Sarkar D. Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer. Int J Mol Sci 2021; 22:ijms22042163. [PMID: 33671547 PMCID: PMC7926723 DOI: 10.3390/ijms22042163] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/01/2021] [Accepted: 02/02/2021] [Indexed: 12/20/2022] Open
Abstract
Obesity is rapidly dispersing all around the world and is closely associated with a high risk of metabolic diseases such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), leading to carcinogenesis, especially hepatocellular carcinoma (HCC). It results from an imbalance between food intake and energy expenditure, leading to an excessive accumulation of adipose tissue (AT). Adipocytes play a substantial role in the tumor microenvironment through the secretion of several adipokines, affecting cancer progression, metastasis, and chemoresistance via diverse signaling pathways. AT is considered an endocrine organ owing to its ability to secrete adipokines, such as leptin, adiponectin, resistin, and a plethora of inflammatory cytokines, which modulate insulin sensitivity and trigger chronic low-grade inflammation in different organs. Even though the precise mechanisms are still unfolding, it is now established that the dysregulated secretion of adipokines by AT contributes to the development of obesity-related metabolic disorders. This review focuses on several obesity-associated adipokines and their impact on obesity-related metabolic diseases, subsequent metabolic complications, and progression to HCC, as well as their role as potential therapeutic targets. The field is rapidly developing, and further research is still required to fully understand the underlying mechanisms for the metabolic actions of adipokines and their role in obesity-associated HCC.
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Affiliation(s)
- Yetirajam Rajesh
- Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA;
| | - Devanand Sarkar
- Massey Cancer Center, Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, VA 23298, USA
- Correspondence: ; Tel.: +1-804-827-2339
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17
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AlZaim I, Hammoud SH, Al-Koussa H, Ghazi A, Eid AH, El-Yazbi AF. Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases. Front Cardiovasc Med 2020; 7:602088. [PMID: 33282920 PMCID: PMC7705180 DOI: 10.3389/fcvm.2020.602088] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 10/22/2020] [Indexed: 12/12/2022] Open
Abstract
Adipose tissue is a critical regulator of systemic metabolism and bodily homeostasis as it secretes a myriad of adipokines, including inflammatory and anti-inflammatory cytokines. As the main storage pool of lipids, subcutaneous and visceral adipose tissues undergo marked hypertrophy and hyperplasia in response to nutritional excess leading to hypoxia, adipokine dysregulation, and subsequent low-grade inflammation that is characterized by increased infiltration and activation of innate and adaptive immune cells. The specific localization, physiology, susceptibility to inflammation and the heterogeneity of the inflammatory cell population of each adipose depot are unique and thus dictate the possible complications of adipose tissue chronic inflammation. Several lines of evidence link visceral and particularly perivascular, pericardial, and perirenal adipose tissue inflammation to the development of metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular diseases. In addition to the implication of the immune system in the regulation of adipose tissue function, adipose tissue immune components are pivotal in detrimental or otherwise favorable adipose tissue remodeling and thermogenesis. Adipose tissue resident and infiltrating immune cells undergo metabolic and morphological adaptation based on the systemic energy status and thus a better comprehension of the metabolic regulation of immune cells in adipose tissues is pivotal to address complications of chronic adipose tissue inflammation. In this review, we discuss the role of adipose innate and adaptive immune cells across various physiological and pathophysiological states that pertain to the development or progression of cardiovascular diseases associated with metabolic disorders. Understanding such mechanisms allows for the exploitation of the adipose tissue-immune system crosstalk, exploring how the adipose immune system might be targeted as a strategy to treat cardiovascular derangements associated with metabolic dysfunctions.
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Affiliation(s)
- Ibrahim AlZaim
- Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon
- Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon
| | - Safaa H. Hammoud
- Department of Pharmacology and Therapeutics, Beirut Arab University, Beirut, Lebanon
| | - Houssam Al-Koussa
- Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon
| | - Alaa Ghazi
- Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon
| | - Ali H. Eid
- Department of Pharmacology and Therapeutics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
- Department of Basic Medical Sciences, College of Medicine, Qatar University, Doha, Qatar
- Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar
| | - Ahmed F. El-Yazbi
- Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
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18
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Ezzati-Mobaser S, Malekpour-Dehkordi Z, Nourbakhsh M, Tavakoli-Yaraki M, Ahmadpour F, Golpour P, Nourbakhsh M. The up-regulation of markers of adipose tissue fibrosis by visfatin in pre-adipocytes as well as obese children and adolescents. Cytokine 2020; 134:155193. [PMID: 32707422 DOI: 10.1016/j.cyto.2020.155193] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 06/25/2020] [Accepted: 07/04/2020] [Indexed: 01/01/2023]
Abstract
Adipocytes are surrounded by a three-dimensional network of extracellular matrix (ECM) proteins. Aberrant ECM accumulation and remodeling leads to adipose tissue fibrosis. Visfatin is one of the adipocytokines that is increased in obesity and is implicated in insulin resistance. The objective of this study was to investigate the effect of visfatin on major components of ECM remodeling. In this study, plasma levels of both endotrophin and visfatin in obese children and adolescents were significantly higher than those in control subjects and they showed a positive correlation with each other. Treatment of 3T3-L1 pre-adipocytes with visfatin caused significant up-regulation of Osteopontin (Opn), Collagen type VI (Col6), matrix metalloproteinases MMP-2 and MMP-9. By using inhibitors of major signaling pathways it was shown that visfatin exerted its effect on Col6a3 gene expression through PI3K, JNK, and NF-кB pathways, while induced Opn gene expression via PI3K, JNK, MAPK/ERK, and NOTCH1. Our conclusion is that, the relationship between visfatin, endotrophin and insulin resistance parameters in obesity as well as increased expression of ECM proteins by visfatin suggests adipose tissue fibrosis as a mechanism for devastating effects of visfatin in obesity.
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Affiliation(s)
- Samira Ezzati-Mobaser
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Malekpour-Dehkordi
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular -Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mona Nourbakhsh
- Hazrat Aliasghar Children's Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Tavakoli-Yaraki
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Ahmadpour
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Pegah Golpour
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mitra Nourbakhsh
- Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Zorena K, Jachimowicz-Duda O, Ślęzak D, Robakowska M, Mrugacz M. Adipokines and Obesity. Potential Link to Metabolic Disorders and Chronic Complications. Int J Mol Sci 2020; 21:E3570. [PMID: 32443588 PMCID: PMC7278967 DOI: 10.3390/ijms21103570] [Citation(s) in RCA: 240] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 05/14/2020] [Accepted: 05/15/2020] [Indexed: 12/19/2022] Open
Abstract
The World Health Organization (WHO) has recognized obesity as one of the top ten threats to human health. It is estimated that the number of obese and overweight people worldwide exceeds the number of those who are undernourished. Obesity is not only a state of abnormally increased adipose tissue in the body, but also of increased release of biologically active adipokines. Adipokines released into the circulating blood, due to their specific receptors on the surface of target cells, act as classic hormones affecting the metabolism of tissues and organs. What is more, adipokines and cytokines may decrease the insulin sensitivity of tissues and induce inflammation and development of chronic complications. Certainly, it can be stated that in an era of a global obesity pandemic, adipokines may gain more and more importance as regards their use in the diagnostic evaluation and treatment of diseases. An extensive search for materials on the role of white, brown and perivascular fatty tissue and obesity-related metabolic and chronic complications was conducted online using PubMed, the Cochrane database and Embase.
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Affiliation(s)
- Katarzyna Zorena
- Department of Immunobiology and Environment Microbiology, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Olga Jachimowicz-Duda
- Independent Public Specialized Health Care Center in Lębork, Department of Internal Diseases, Węgrzynowicza 13, 84-300 Lębork, Poland;
| | - Daniel Ślęzak
- Department of Emergency Medicine, Faculty of Health Sciences, Medical University of Gdańsk, Smoluchowskiego 17, 80-214 Gdańsk, Poland;
| | - Marlena Robakowska
- Department of Public Health & Social Medicine, Faculty of Health Sciences, Medical University of Gdańsk, Al. Zwycięctwa 42a, 80-210 Gdańsk, Poland;
| | - Małgorzata Mrugacz
- Department of Ophthalmology and Eye Rehabilitation, Medical University of Bialystok, Kilinskiego 1, 15-089 Białystok, Poland;
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de Guia RM, Agerholm M, Nielsen TS, Consitt LA, Søgaard D, Helge JW, Larsen S, Brandauer J, Houmard JA, Treebak JT. Aerobic and resistance exercise training reverses age-dependent decline in NAD + salvage capacity in human skeletal muscle. Physiol Rep 2020; 7:e14139. [PMID: 31207144 PMCID: PMC6577427 DOI: 10.14814/phy2.14139] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 05/08/2019] [Indexed: 12/18/2022] Open
Abstract
Aging decreases skeletal muscle mass and strength, but aerobic and resistance exercise training maintains skeletal muscle function. NAD+ is a coenzyme for ATP production and a required substrate for enzymes regulating cellular homeostasis. In skeletal muscle, NAD+ is mainly generated by the NAD+ salvage pathway in which nicotinamide phosphoribosyltransferase (NAMPT) is rate‐limiting. NAMPT decreases with age in human skeletal muscle, and aerobic exercise training increases NAMPT levels in young men. However, whether distinct modes of exercise training increase NAMPT levels in both young and old people is unknown. We assessed the effects of 12 weeks of aerobic and resistance exercise training on skeletal muscle abundance of NAMPT, nicotinamide riboside kinase 2 (NRK2), and nicotinamide mononucleotide adenylyltransferase (NMNAT) 1 and 3 in young (≤35 years) and older (≥55 years) individuals. NAMPT in skeletal muscle correlated negatively with age (r2 = 0.297, P < 0.001, n = 57), and VO2peak was the best predictor of NAMPT levels. Moreover, aerobic exercise training increased NAMPT abundance 12% and 28% in young and older individuals, respectively, whereas resistance exercise training increased NAMPT abundance 25% and 30% in young and in older individuals, respectively. None of the other proteins changed with exercise training. In a separate cohort of young and old people, levels of NAMPT, NRK1, and NMNAT1/2 in abdominal subcutaneous adipose tissue were not affected by either age or 6 weeks of high‐intensity interval training. Collectively, exercise training reverses the age‐dependent decline in skeletal muscle NAMPT abundance, and our findings highlight the value of exercise training in ameliorating age‐associated deterioration of skeletal muscle function.
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Affiliation(s)
- Roldan M de Guia
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Marianne Agerholm
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Thomas S Nielsen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Leslie A Consitt
- Department of Biomedical Sciences, Ohio Musculoskeletal and Neurological Institute, Diabetes Institute, Ohio University, Athens, Ohio
| | - Ditte Søgaard
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jørn W Helge
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Steen Larsen
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Josef Brandauer
- Department of Health Sciences, Gettysburg College, Gettysburg, Pennsylvania
| | - Joseph A Houmard
- Department of Kinesiology, Human Performance Laboratory, East Carolina University, Greenville, North Carolina.,East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina
| | - Jonas T Treebak
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Audrito V, Messana VG, Deaglio S. NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation. Front Oncol 2020; 10:358. [PMID: 32266141 PMCID: PMC7096376 DOI: 10.3389/fonc.2020.00358] [Citation(s) in RCA: 138] [Impact Index Per Article: 27.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 03/02/2020] [Indexed: 12/13/2022] Open
Abstract
Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT) are two intracellular enzymes that catalyze the first step in the biosynthesis of NAD from nicotinamide and nicotinic acid, respectively. By fine tuning intracellular NAD levels, they are involved in the regulation/reprogramming of cellular metabolism and in the control of the activity of NAD-dependent enzymes, including sirtuins, PARPs, and NADases. However, during evolution they both acquired novel functions as extracellular endogenous mediators of inflammation. It is well-known that cellular stress and/or damage induce release in the extracellular milieu of endogenous molecules, called alarmins or damage-associated molecular patterns (DAMPs), which modulate immune functions through binding pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), and activate inflammatory responses. Increasing evidence suggests that extracellular (e)NAMPT and eNAPRT are novel soluble factors with cytokine/adipokine/DAMP-like actions. Elevated eNAMPT were reported in several metabolic and inflammatory disorders, including obesity, diabetes, and cancer, while eNAPRT is emerging as a biomarker of sepsis and septic shock. This review will discuss available data concerning the dual role of this unique family of enzymes.
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Affiliation(s)
- Valentina Audrito
- Laboratory of Tumor Immunogenetics, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Vincenzo Gianluca Messana
- Laboratory of Tumor Immunogenetics, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Silvia Deaglio
- Laboratory of Tumor Immunogenetics, Department of Medical Sciences, University of Turin, Turin, Italy
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22
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Potential role of adipose tissue and its hormones in burns and critically III patients. Burns 2020; 46:259-266. [DOI: 10.1016/j.burns.2019.01.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Revised: 12/17/2018] [Accepted: 01/30/2019] [Indexed: 12/26/2022]
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Huang X, Wang C, Tian S, Huang R, Guo D, Zhang H, Shi J, Wang S. Higher Plasma Level of Nampt Presaging Memory Dysfunction in Chinese Type 2 Diabetes Patients with Mild Cognitive Impairment. J Alzheimers Dis 2019; 70:303-314. [PMID: 31177228 DOI: 10.3233/jad-190269] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Xi Huang
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China
| | - Chenchen Wang
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China
- Medical School of Southeast University, Nanjing, PR China
| | - Sai Tian
- Medical School of Southeast University, Nanjing, PR China
| | - Rong Huang
- Medical School of Southeast University, Nanjing, PR China
| | - Dan Guo
- Medical School of Southeast University, Nanjing, PR China
| | - Haoqiang Zhang
- Medical School of Southeast University, Nanjing, PR China
| | - Jijing Shi
- Medical School of Southeast University, Nanjing, PR China
| | - Shaohua Wang
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China
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24
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The Role of Adipose Tissue in the Pathogenesis and Therapeutic Outcomes of Inflammatory Bowel Disease. Cells 2019; 8:cells8060628. [PMID: 31234447 PMCID: PMC6627060 DOI: 10.3390/cells8060628] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 06/16/2019] [Accepted: 06/18/2019] [Indexed: 02/06/2023] Open
Abstract
Though historically regarded as an inert energy store, adipose tissue is a complex endocrine organ, which is increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD). Accumulating evidence points to visceral adipose tissue and specifically to its mesenteric component, or “creeping fat” as impacting on the disease course through its immunomodulatory properties. On the one hand, mesenteric fat acts as a physical barrier to inflammation and is involved in controlling host immune response to translocation of gut bacteria. On the other hand, however, there exists a strong link between visceral fat and complicated course of the disease with unfavorable therapeutic outcomes. Furthermore, “creeping fat” appears to play different roles in different IBD phenotypes, with the greatest pathogenetic contribution probably to an ileal form of Crohn’s disease. In this review, we summarize and discuss the existing literature on the subject and identify high-priority areas for future research. It may be that a better understanding of the role of mesenteric fat in IBD will determine new therapeutic targets and translate into improved clinical outcomes.
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Adipocytokines in Rheumatoid Arthritis: The Hidden Link between Inflammation and Cardiometabolic Comorbidities. J Immunol Res 2018; 2018:8410182. [PMID: 30584543 PMCID: PMC6280248 DOI: 10.1155/2018/8410182] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 07/19/2018] [Accepted: 10/11/2018] [Indexed: 02/07/2023] Open
Abstract
Rheumatoid arthritis is a chronic autoimmune disease affecting typically synovial joints and leading to progressive articular damage, disability, and reduced quality of life. Despite better recent therapeutic strategies improving long-term outcomes, RA is associated with a high rate of comorbidities, infections, malignancies, and cardiovascular disease (CVD). Remarkably, some well-known pathogenic proinflammatory mediators in RA, such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF), may play a pivotal role in the development of CVD. Interestingly, different preclinical and clinical studies have suggested that biologic agents commonly used to treat RA patients may be effective in improving CVD. In this context, the contribution of adipocytokines has been suggested. Adipocytokines are pleiotropic molecules, mainly released by white adipose tissue and immune cells. Adipocytokines modulate the function of different tissues and cells, and in addition to energy homeostasis and metabolism, amplify inflammation, immune response, and tissue damage. Adipocytokines may contribute to the proinflammatory state in RA patients and development of bone damage. Furthermore, they could be associated with the occurrence of CVD. In this study, we reviewed available evidence about adipocytokines in RA, because of their involvement in disease activity, associated CVD, and possible biomarkers of prognosis and treatment outcome and because of their potential as a possible new therapeutic target.
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26
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Xia MF, Lin HD, Chen LY, Wu L, Ma H, Li Q, Aleteng Q, Chen Y, Sun YX, Hu Y, Pan BS, Li XY, Gao X. Association of visceral adiposity and its longitudinal increase with the risk of diabetes in Chinese adults: A prospective cohort study. Diabetes Metab Res Rev 2018; 34:e3048. [PMID: 30035847 DOI: 10.1002/dmrr.3048] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 07/04/2018] [Accepted: 07/15/2018] [Indexed: 12/31/2022]
Abstract
OBJECTIVE A Chinese visceral adiposity index (CVAI) was recently established to estimate the visceral fat area in Chinese adults. This study aimed to investigate the risk of incident prediabetes and diabetes in relation to visceral adiposity calculated by CVAI. METHODS A total of 2558 subjects with normal plasma glucose levels from the Shanghai Changfeng Study were enrolled in a prospective cohort study. The independent associations of basal visceral fat area by CVAI and its longitudinal change with incident prediabetes and diabetes were identified using Cox regression analyses. RESULTS During an average of 4.4 years of follow-up, 546 (21.3%) and 99 (3.9%) of 2558 nondiabetic subjects developed prediabetes and diabetes, respectively. Visceral fat area by CVAI and its longitudinal increase were independently associated with incident prediabetes and diabetes in Chinese adults. In a multivariable-adjusted regression model, CVAI, as well as its annual change, was the strongest independent predictor of incident prediabetes (HR, 1.383 [1.162-1.647]) and diabetes (HR, 1.607 [1.092-2.364]) compared with other estimates of obesity (BMI and waist circumference). Receiver operating characteristic curve analyses showed that CVAI had better performance than BMI and waist circumference for the prediction of prediabetes and diabetes in Chinese adults. CONCLUSIONS Visceral adiposity plays a pivotal role in the pathogenesis of diabetes, and the visceral adiposity estimated by CVAI is superior to the traditional estimates of obesity for the prediction of incident prediabetes and diabetes in Chinese adults.
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Affiliation(s)
- Ming-Feng Xia
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
| | - Huan-Dong Lin
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
| | - Ling-Yan Chen
- Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li Wu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
| | - Hui Ma
- Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qian Li
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
| | - Qiqige Aleteng
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
| | - Ying Chen
- Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Yi-Xuan Sun
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
| | - Yu Hu
- Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Bai-Shen Pan
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiao-Ying Li
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China
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Oikonomou EK, Antoniades C. Immunometabolic Regulation of Vascular Redox State: The Role of Adipose Tissue. Antioxid Redox Signal 2018; 29:313-336. [PMID: 28657335 DOI: 10.1089/ars.2017.7017] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
SIGNIFICANCE Vascular oxidative stress plays a crucial role in atherogenesis and cardiovascular disease (CVD). Recent evidence suggests that vascular redox state is under the control of complex pathophysiological mechanisms, ranging from inflammation to obesity and insulin resistance (IR). Recent Advances: Adipose tissue (AT) is now recognized as a dynamic endocrine and paracrine organ that secretes several bioactive molecules, called adipokines. AT has recently been shown to regulate vascular redox state in both an endocrine and a paracrine manner through the secretion of adipokines, therefore providing a mechanistic link for the association between obesity, IR, inflammation, and vascular disease. Importantly, AT behaves as a sensor of cardiovascular oxidative stress, modifying its secretory profile in response to cardiovascular oxidative injury. CRITICAL ISSUES The present article presents an up-to-date review of the association between AT and vascular oxidative stress. We focus on the effects of individual adipokines on modulating reactive oxygen species production and scavenging in the vascular wall. In addition, we highlight how inflammation, obesity, and IR alter the biology and secretome of AT leading to a more pro-oxidant phenotype with a particular focus on the local regulatory mechanisms of perivascular AT driven by vascular oxidation. FUTURE DIRECTIONS The complex and dynamic biology of AT, as well as its importance in the regulation of vascular redox state, provides numerous opportunities for the development of novel, targeted treatments in the management of CVD. Therapeutic modulation of AT biology could improve vascular redox state affecting vascular disease pathogenesis. Antioxid. Redox Signal. 29, 313-336.
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Affiliation(s)
- Evangelos K Oikonomou
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford , Oxford, United Kingdom
| | - Charalambos Antoniades
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford , Oxford, United Kingdom
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Dalamaga M, Christodoulatos GS, Mantzoros CS. The role of extracellular and intracellular Nicotinamide phosphoribosyl-transferase in cancer: Diagnostic and therapeutic perspectives and challenges. Metabolism 2018; 82:72-87. [PMID: 29330025 DOI: 10.1016/j.metabol.2018.01.001] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 12/23/2017] [Accepted: 01/04/2018] [Indexed: 02/07/2023]
Abstract
Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties. Nampt is upregulated in many malignancies, including obesity-associated cancers, and is associated with worse prognosis. Serum Nampt may be a potential diagnostic and prognostic biomarker in cancer. Pharmacologic agents that neutralize Nampt or medications that decrease Nampt levels or downregulate signaling pathways downstream of Nampt may prove to be useful anti-cancer treatments. In particular, Nampt inhibitors as monotherapy or in combination therapy have displayed anti-cancer activity in vivo and in vitro. The aim of this review is to explore the role of Nampt in cancer pathophysiology as well as to synopsize the mechanisms underlying the association between extracellular and intracellular Nampt, and malignancy. Exploring the interplay of cellular bioenergetics, inflammation and adiposopathy is expected to be of importance in the development of preventive and therapeutic strategies against cancer.
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Affiliation(s)
- Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527 Athens, Greece.
| | - Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527 Athens, Greece; Department of Microbiology, KAT Hospital, Nikis 2, Kifisia, 14561 Athens, Greece
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA
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Dias S, Paredes S, Ribeiro L. Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue. Int J Endocrinol 2018; 2018:2637418. [PMID: 29593789 PMCID: PMC5822899 DOI: 10.1155/2018/2637418] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 09/28/2017] [Accepted: 10/11/2017] [Indexed: 12/15/2022] Open
Abstract
Metabolic syndrome can be defined as a state of disturbed metabolic homeostasis characterized by visceral obesity, atherogenic dyslipidemia, arterial hypertension, and insulin resistance. The growing prevalence of metabolic syndrome will certainly contribute to the burden of cardiovascular disease. Obesity and dyslipidemia are main features of metabolic syndrome, and both can present with adipose tissue dysfunction, involved in the pathogenic mechanisms underlying this syndrome. We revised the effects, and underlying mechanisms, of the current approved drugs for dyslipidemia and obesity (fibrates, statins, niacin, resins, ezetimibe, and orlistat; sibutramine; and diethylpropion, phentermine/topiramate, bupropion and naltrexone, and liraglutide) on adipose tissue. Specifically, we explored how these drugs can modulate the complex pathways involved in metabolism, inflammation, atherogenesis, insulin sensitivity, and adipogenesis. The clinical outcomes of adipose tissue modulation by these drugs, as well as differences of major importance for clinical practice between drugs of the same class, were identified. Whether solutions to these issues will be found in further adjustments and combinations between drugs already in use or necessarily in new advances in pharmacology is not known. To better understand the effect of drugs used in dyslipidemia and obesity on adipose tissue not only is challenging for physicians but could also be the next step to tackle cardiovascular disease.
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Affiliation(s)
- Sofia Dias
- Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Sílvia Paredes
- Department of Endocrinology, Hospital de Braga, 4710-243 Braga, Portugal
- Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Laura Ribeiro
- Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- I3S-Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal
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Yan N, Yang W, Dong X, Fang Q, Gong Y, Zhou JL, Xu JJ. Promotion of anoxia-reoxygenation-induced inflammation and permeability enhancement by nicotinamide phosphoribosyltransferase-activated MAPK signaling in human umbilical vein endothelial cells. Exp Ther Med 2017; 14:4595-4601. [PMID: 29104667 DOI: 10.3892/etm.2017.5083] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 05/19/2017] [Indexed: 01/02/2023] Open
Abstract
Previous studies have demonstrated that nicotinamide phosphoribosyltransferase (NAMPT) promoted inflammation and permeability of vascular endothelial cells following cardiopulmonary bypass (CPB). In addition, mitogen-activated protein kinase (MAPK) signaling was activated and contributed to these cell responses. However, the mechanism by which NAMPT regulates cellular inflammation and permeability remains unknown, and whether NAMPT regulates MAPK signaling during this process is also not clear. The present study established an anoxia-reoxygenation (A-R) model using human umbilical vein endothelial cells (HUVECs) and investigated the regulation of MAPK signaling by NAMPT by using small RNA transfection, ELISA and western blot analysis. The results demonstrated that A-R significantly induced the expression levels of NAMPT and cellular permeability-associated proteins, and the release of several inflammatory factors. Furthermore, calcium and MAPK signaling were evidently increased. When the A-R cells were transfected with NAMPT small interfering RNA, the expression of cellular permeability-associated proteins was downregulated, the release of inflammatory factors was decreased, and calcium and MAPK signaling was blocked. These data suggest that NAMPT may activate MAPK signaling to promote A-R-induced inflammation and permeability enhancement of HUVECs. Therefore, the current study indicates that NAMPT may be a potential drug target for A-R-induced endothelial cell injury subsequent to CPB.
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Affiliation(s)
- Nao Yan
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Wei Yang
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Xiao Dong
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Qiao Fang
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Yi Gong
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Jian-Liang Zhou
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Jian-Jun Xu
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
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Javanmard SH, Dehghananzadeh R, Rafiee L, Naji H, Rezayat A, Sarrafzadegan N. Genetic associations of the visfatin G-948T polymorphism with obesity-related metabolic traits in an Iranian population. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2017; 21:105. [PMID: 28250782 PMCID: PMC5322690 DOI: 10.4103/1735-1995.193177] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 08/21/2016] [Accepted: 09/05/2016] [Indexed: 11/22/2022]
Abstract
Background: Obesity is a global public health problem. Visfatin, as an adipocytokine, is coded by a gene known as nicotinamide phosphoribosyltransferase. So far, results were conflicted regarding correlations of visfatin with obesity and metabolic variables. The present study aimed to explore the association between G-948T polymorphism of visfatin gene with obesity and lipid profile in a nationally representative sample of Iranian population. Materials and Methods: In this case–control study, we assessed 129 randomly selected patients with obesity and 182 healthy normal weight controls from participants of Isfahan Healthy Heart Program. Genomic DNA was isolated from peripheral blood cells, and high-resolution melt polymerase chain reaction was performed to explore the presence of G-948T polymorphism. Results: T carriers “GT + TT” were statistically more frequent in the obese patients than the controls (P = 0.013; odds ratio = 1.9, 95% confidence interval = 1.1–3.1). The serum levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly different between T carriers and GG homozygote genotype (P = 0.03 and 0.02, respectively). Conclusion: We concluded that visfatin G-948T polymorphism was correlated with obesity, total cholesterol, and LDL-C levels in our population.
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Affiliation(s)
- Shaghayegh Haghjooy Javanmard
- Applied Physiology Research Centre, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Raheleh Dehghananzadeh
- Applied Physiology Research Centre, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Laleh Rafiee
- Applied Physiology Research Centre, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hajar Naji
- Applied Physiology Research Centre, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Azadeh Rezayat
- Applied Physiology Research Centre, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nizal Sarrafzadegan
- Isfahan Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
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Owczarek AJ, Olszanecka-Glinianowicz M, Kocełak P, Bożentowicz-Wikarek M, Brzozowska A, Mossakowska M, Puzianowska-Kuźnicka M, Grodzicki T, Więcek A, Chudek J. The relationship between circulating visfatin/nicotinamide phosphoribosyltransferase, obesity, inflammation and lipids profile in elderly population, determined by structural equation modeling. Scand J Clin Lab Invest 2016; 76:632-640. [PMID: 27712122 DOI: 10.1080/00365513.2016.1230884] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Revised: 08/07/2016] [Accepted: 08/28/2016] [Indexed: 01/21/2023]
Abstract
BACKGROUND The available literature suggests that circulating visfatin/Nicotinamide Phosphoribosyltransferase (NAMPT) level variability in humans is related to obesity, insulin resistance, inflammation, and lipid profile. The aim of the study was to assess the relationship between circulating visfatin/NAMPT, obesity, insulin resistance, inflammation, and lipid profile in a large population-based, elderly cohort, applying structural equation modeling. MATERIALS AND METHODS The analysis included 2983 elderly participants of the PolSenior study with assessed total blood count, fasting concentrations of lipids, glucose, insulin, hs-CRP, interleukin-6, and visfatin/NAMPT (by ELISA), and calculated HOMA-IR. RESULTS The circulating visfatin/NAMPT levels were higher in obese compared to normal weight subjects, in those with hs-CRP above 3 mg/L, with low serum HDL cholesterol, and in insulin resistant subjects. Based on results of the exploratory factor analysis, a baseline model of mutual relationship between four latent and measured variables was created and a final model was developed by maintaining only two significant categories. The important variables for 'latent inflammation' proved to be hs-CRP and IL-6 serum levels. In the case of 'nutritional status', important variables were BMI, waist circumference, and to a lesser extent insulin resistance. Additionally, the residual correlation between those two constructs was also statistically significant. CONCLUSION The structural equation modeling provided support for the existence of a link between nutritional status, inflammation and circulating visfatin/NAMPT level. This indicates that circulating visfatin/NAMPT can be considered as a novel surrogate marker of systemic inflammation associated with fat depot, especially visceral, in the elderly population.
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Affiliation(s)
- Aleksander J Owczarek
- a Department of Statistics, Department of Instrumental Analysis, Faculty of Pharmacy and Laboratory Medicine in Sosnowiec , Medical University of Silesia , Katowice , Poland
| | - Magdalena Olszanecka-Glinianowicz
- b Health Promotion and Obesity Management Unit, Department of Pathophysiology , Medical Faculty in Katowice, Medical University of Silesia , Katowice , Poland
| | - Piotr Kocełak
- b Health Promotion and Obesity Management Unit, Department of Pathophysiology , Medical Faculty in Katowice, Medical University of Silesia , Katowice , Poland
| | - Maria Bożentowicz-Wikarek
- c Pathophysiology Unit, Department of Pathophysiology , Medical Faculty in Katowice, Medical University of Silesia , Katowice , Poland
| | - Aniceta Brzozowska
- b Health Promotion and Obesity Management Unit, Department of Pathophysiology , Medical Faculty in Katowice, Medical University of Silesia , Katowice , Poland
| | | | - Monika Puzianowska-Kuźnicka
- e Department of Human Epigenetics , Mossakowski Medical Research Centre , Warsaw , Poland
- f Department of Geriatrics and Gerontology , Medical Center of Postgraduate Education , Warsaw , Poland
| | - Tomasz Grodzicki
- g Department of Internal Medicine and Gerontology , Jagiellonian University Medical College , Krakow , Poland
| | - Andrzej Więcek
- h Department of Nephrology, Transplantation and Internal Medicine, Medical Faculty in Katowice , Medical University of Silesia , Katowice , Poland
| | - Jerzy Chudek
- c Pathophysiology Unit, Department of Pathophysiology , Medical Faculty in Katowice, Medical University of Silesia , Katowice , Poland
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Santangelo C, Filesi C, Varì R, Scazzocchio B, Filardi T, Fogliano V, D'Archivio M, Giovannini C, Lenzi A, Morano S, Masella R. Consumption of extra-virgin olive oil rich in phenolic compounds improves metabolic control in patients with type 2 diabetes mellitus: a possible involvement of reduced levels of circulating visfatin. J Endocrinol Invest 2016; 39:1295-1301. [PMID: 27344308 DOI: 10.1007/s40618-016-0506-9] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 06/16/2016] [Indexed: 12/11/2022]
Abstract
AIM Phenolic compounds naturally contained in extra-virgin olive oil (EVOO) have demonstrated anti-inflammatory and antioxidant properties. The present study aimed at evaluating the effects of a polyphenol-rich extra-virgin olive oil (EVOO) (high-polyphenol EVOO, HP-EVOO) on the metabolic control and the production of specific pro-/anti-inflammatory adipokines in overweight patients with type 2 diabetes mellitus (T2D). METHODS Eleven overweight T2D patients not in treatment with insulin were invited to follow their habitual diet for a total of 8 weeks. During the first 4 weeks (wash-out period), they were asked to consume refined olive oil (ROO, polyphenols not detectable) and then to replace ROO with HP-EVOO (25 mL/day, 577 mg of phenolic compounds/kg) for the remaining 4 weeks. Anthropometric parameters, fasting glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein, plasma lipid profile, liver function and serum levels of TNF-α, IL-6, adiponectin, visfatin and apelin were assessed at the end of each 4-week period. RESULTS HP-EVOO consumption significantly reduced fasting plasma glucose (P = 0.023) and HbA1c (P = 0.039) levels as well as BMI (P = 0.012) and body weight (P = 0.012). HP-EVOO ingestion determined a reduction in serum level of aspartate aminotransferase (AST, P = 0.0056) and alanine aminotransferase (ALT, P = 0.024). Serum visfatin levels strongly decreased after HP-EVOO ingestion (P = 0.0021). CONCLUSIONS Daily consumption of polyphenol-rich EVOO might improve metabolic control and circulating inflammatory adipokines profile in overweight T2D patients.
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Affiliation(s)
- C Santangelo
- Unit of Nutrition, Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy.
| | - C Filesi
- Unit of Nutrition, Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy
| | - R Varì
- Unit of Nutrition, Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy
| | - B Scazzocchio
- Unit of Nutrition, Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy
| | - T Filardi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - V Fogliano
- Food Quality and Design Group, Wageningen University, Wageningen, The Netherlands
| | - M D'Archivio
- Unit of Nutrition, Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy
| | - C Giovannini
- Unit of Nutrition, Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy
| | - A Lenzi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - S Morano
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | - R Masella
- Unit of Nutrition, Department of Veterinary Public Health and Food Safety, Italian National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy
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Novak S, Divkovic D, Drenjancevic I, Cosic A, Selthofer-Relatic K. Visfatin serum level and expression in subcutaneous and visceral adipose tissue in prepubertal boys. Pediatr Obes 2016; 11:411-7. [PMID: 26486101 DOI: 10.1111/ijpo.12080] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 09/04/2015] [Accepted: 09/17/2015] [Indexed: 12/31/2022]
Abstract
BACKGROUND The biological role of visfatin in humans, especially in eutrophic and healthy children, is not understood yet, except for its link to obesity-related disorders in adolescents and adults. OBJECTIVES To determine the physiological values of serum visfatin concentrations, and visfatin mRNA expression in subcutaneous (SAT) and visceral adipose tissue (VAT), and to correlate them with anthropometric/metabolic data in prepubertal healthy boys. METHODS The study included 59 healthy boys, age 1-10 years, hospitalized for elective surgery, divided according to age into group I (1-3 years old), group II (3-7 years old) and group III (7-10 years old). Anthropometric and biochemical measurements, and the visfatin serum and mRNA level in SAT and VAT were determined in all patients. RESULTS Visfatin mRNA expression was higher in SAT compared with VAT in all three studied groups. Highest visfatin mRNA was found in SAT of group III compared with group II (P = 0.030). VAT visfatin mRNA expression negatively correlates with body weight (P = 0.039), waist circumference (P = 0.027) and morning glucose level (P = 0.007). CONCLUSION Lack of changes in serum visfatin level despite the changes in visfatin mRNA expression of adipose tissue suggests paracrine effect of visfatin rather than endocrine. Negative correlation of visfatin VAT mRNA expression with anthropometric parameters indicates important role of VAT visfatin in maturation and in glucose metabolism.
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Affiliation(s)
- S Novak
- Department for Physiology and Immunology, Faculty of Medicine, University of Osijek, Osijek, Croatia
| | - D Divkovic
- Department for Childhood Surgery, Osijek University Hospital, Osijek, Croatia
| | - I Drenjancevic
- Department for Physiology and Immunology, Faculty of Medicine, University of Osijek, Osijek, Croatia
| | - A Cosic
- Department for Physiology and Immunology, Faculty of Medicine, University of Osijek, Osijek, Croatia
| | - K Selthofer-Relatic
- Department for Cardiovascular Diseases, Osijek University Hospital, Osijek, Croatia.
- Department for Internal Medicine, Faculty of Medicine, University of Osijek, Osijek, Croatia.
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Berezin AE, Samura TA, Kremzer AA, Berezina TA, Martovitskaya YV, Gromenko EA. An association of serum vistafin level and number of circulating endothelial progenitor cells in type 2 diabetes mellitus patients. Diabetes Metab Syndr 2016; 10:205-212. [PMID: 27377688 DOI: 10.1016/j.dsx.2016.06.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Accepted: 06/06/2016] [Indexed: 01/11/2023]
Abstract
BACKGROUND The decreased number and impaired functions of endothelial progenitor cells (EPCs) may associate with cardiovascular disease (CV) including atherosclerosis. However, the role of vistafin in regulation of angiogenic EPC subset maturation in T2DM patients without known atherosclerosis is still not fully understood. THE AIM OF THE STUDY To investigate an association of serum vistafin level and number of circulating EPCs in T2DM patients beyond known CV disease. METHODS This case-control observational investigation was evolved 54 subjects with T2DM and 35 healthy volunteers. The flow cytometry was used for predictably distinguishing cell subsets, which depend on expression of CD45, CD34, CD14, Tie-2, and VEGFR2. Biomarkers were measured at baseline of the study. RESULTS All T2DM patients were divided depending median of vistafin level (5.88ng/mL) in to two cohorts with low vistafin level (<5.88ng/mL; n=29) and high vistafin level (≥5.88ng/mL; n=25) respectively. Logistic regression analysis has shown that visfatin, hs-CRP, age and BMI were the best variables in the prediction of EPC number labeled as CD14+CD309+ and CD14+CD309+Tie2+ cells. After adjustment of the model to age and BMI elevated visfatin level remained the best predictor for both CD14+CD309+ and CD14+CD309+Tie2+ EPCs (OR 0.92, 95% CI: 0.88-0.95; P=0.001 and OR 0.90, 95% CI: 0.87-0.96; P=0.001 respectively). CONCLUSION We found that elevated level of vistafin was an independent predictor for declined numerous of non-classical EPCs labeled as CD14+CD309+ and CD14+CD309+Tie2+, whereas CD34+ subsets of EPCs did not associate with vistafin level in T2DM individuals.
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Affiliation(s)
- Alexander E Berezin
- Internal Medicine Department, State Medical University, 26, Mayakovsky Av., Zaporozhye, Postcode 69035, Ukraine.
| | - Tatyana A Samura
- Clinical Pharmacology Department, State Medical University, Zaporozhye, Ukraine
| | - Alexander A Kremzer
- Clinical Pharmacology Department, State Medical University, Zaporozhye, Ukraine
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Ilhan TT, Kebapcilar A, Yilmaz SA, Ilhan T, Kerimoglu OS, Pekin AT, Akyurek F, Unlu A, Celik C. Relations of Serum Visfatin and Resistin Levels with Endometrial Cancer and Factors Associated with its Prognosis. Asian Pac J Cancer Prev 2016; 16:4503-8. [PMID: 26107194 DOI: 10.7314/apjcp.2015.16.11.4503] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The aims of this study were compare the serum visfatin and resistin levels between endometrial cancer (EC) patients and controls and evaluate their power to predict prognosis. MATERIALS AND METHODS This prospective study was conducted between March 2013 to June 2014 on the Gynecologic Oncology Department of the University of Selcuk, Konya, Turkey. A total of 42 EC patients and 42 controls were included and assessed for differences in serum visfatin and resistin levels, along with prognostic factors. RESULTS Endometrial cancer patients had significantly higher visfatin levels than control s (p: 0.011), associated with deep myometrial invasion (p: 0.019). In contrast the serum level of resistin did not significantly differ between EC patients and controls (p: 0.362). However, high resistin level in EC patients was associated with increase lymph node metastasis (p: 0.009). On logistic regression analysis, we found that serum visfatin elevation was associated with risk of myometrial invasion (OR: 1,091; 95%CI: 1.021- 1.166; p: 0.010) and serum resistin with risk of lymph node metastasis (OR: 1.018; 95%CI: 1.000- 1.035; p: 0.046). For myometrial invasion prediction, a serum visfatin level greater than 26.8 ng/mL demonstrated a sensitivity and specificity of 66.6 % and 96.4%, respectively. For lymph node metastasis prediction, the best cut-off for serum resistin level was 599ng/mL. A serum resistin level greater than this demonstrated a sensitivity and specificity of 87.5% and 77.1%, respectively. CONCLUSIONS Our data suggest that serum visfatin is elevated in patients with EC and serum visfatin and resistin levels could be used to predict the risk of advance stage lesions.
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Affiliation(s)
- Tolgay Tuyan Ilhan
- Gynecologic Oncology, Medical Faculty, University of Selcuk, Turkey E-mail :
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Nagy K, Nagaraju SP, Rhee CM, Mathe Z, Molnar MZ. Adipocytokines in renal transplant recipients. Clin Kidney J 2016; 9:359-73. [PMID: 27274819 PMCID: PMC4886901 DOI: 10.1093/ckj/sfv156] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 12/18/2015] [Indexed: 02/07/2023] Open
Abstract
In the last two decades, perceptions about the role of body fat have changed. Adipocytes modulate endocrine and immune homeostasis by synthesizing hundreds of hormones, known as adipocytokines. Many studies have been investigating the influences and effects of these adipocytokines and suggest that they are modulated by the nutritional and immunologic milieu. Kidney transplant recipients (KTRs) are a unique and relevant population in which the function of adipocytokines can be examined, given their altered nutritional and immune status and subsequent dysregulation of adipocytokine metabolism. In this review, we summarize the recent findings about four specific adipocytokines and their respective roles in KTRs. We decided to evaluate the most widely described adipocytokines, including leptin, adiponectin, visfatin and resistin. Increasing evidence suggests that these adipocytokines may lead to cardiovascular events and metabolic changes in the general population and may also increase mortality and graft loss rate in KTRs. In addition, we present findings on the interrelationship between serum adipocytokine levels and nutritional and immunologic status, and mechanisms by which adipocytokines modulate morbidity and outcomes in KTRs.
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Affiliation(s)
- Kristof Nagy
- Department of Transplantation and Surgery , Semmelweis University , Budapest , Hungary
| | | | - Connie M Rhee
- Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension , University of California Irvine , Orange, CA , USA
| | - Zoltan Mathe
- Department of Transplantation and Surgery , Semmelweis University , Budapest , Hungary
| | - Miklos Z Molnar
- Division of Nephrology, Department of Medicine , University of Tennessee Health Science Center , Memphis, TN , USA
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Qu S, Mo L, Niu Y, Sun X, Li H, Wang Z, Xu W, Rong A. Expression of visfatin in the diabetic rat retina. Clin Exp Ophthalmol 2016; 44:251-9. [PMID: 26694625 DOI: 10.1111/ceo.12692] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 12/01/2015] [Accepted: 12/11/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Visfatin has been found in adipose tissue, liver and kidney of healthy and diabetic people, with its expression being increased in the aforementioned tissues in diabetes. Based on the former researches, visfatin may exist in the retina and affect the development of diabetic retinopathy. The expression of visfatin in Sprague-Dawley rats' retina, which may carve a path to study the pathogenesis of diabetic retinopathy, was investigated by this study. METHODS The mRNA and protein expression of visfatin in Sprague-Dawley rats' retina were detected by the reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Immunohistochemical staining was applied to detect the expression location of visfatin in the rats' retinas. RESULTS The mRNA and visfatin protein expressions in both normal and streptozocin-induced diabetic rats' retina increased significantly in 2 to 8 weeks of diabetes mellitus (DM). Compared with the normal control groups, the difference was statistically significant (P < 0.05). The histological examination showed that the retinal thickness decreased gradually over the course of DM and the decrease in the outer nuclear layer was the most obvious. At 4 and 8 weeks, the decrease in the retinal thickness was significant (P < 0.01). Visfatin was expressed in the retinal nerve fibre layer, inner plexiform layer and outer plexiform layer, and with the progression of DM, its expression was increased. CONCLUSIONS Visfatin was expressed in the rats' retinas, mainly in the retinal nerve fibre layer, inner plexiform layer and outer plexiform layer. As the development of DM course, its expression was gradually increased.
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Affiliation(s)
- Shen Qu
- Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lijuan Mo
- Department of Ophthalmology, Putuo District Centre Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yunli Niu
- Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaoting Sun
- University of Nebraska Medical Centre, Omaha, Nebraska, USA
| | - Houshuo Li
- Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhen Wang
- Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wei Xu
- Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ao Rong
- Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
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Saad MI, Abdelkhalek TM, Saleh MM, Kamel MA, Youssef M, Tawfik SH, Dominguez H. Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells. Endocrine 2015; 50:537-67. [PMID: 26271514 DOI: 10.1007/s12020-015-0709-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 07/25/2015] [Indexed: 12/13/2022]
Abstract
Diabetes mellitus is a heterogeneous, multifactorial, chronic disease characterized by hyperglycemia owing to insulin insufficiency and insulin resistance (IR). Recent epidemiological studies showed that the diabetes epidemic affects 382 million people worldwide in 2013, and this figure is expected to be 600 million people by 2035. Diabetes is associated with microvascular and macrovascular complications resulting in accelerated endothelial dysfunction (ED), atherosclerosis, and cardiovascular disease (CVD). Unfortunately, the complex pathophysiology of diabetic cardiovascular damage is not fully understood. Therefore, there is a clear need to better understand the molecular pathophysiology of ED in diabetes, and consequently, better treatment options and novel efficacious therapies could be identified. In the light of recent extensive research, we re-investigate the association between diabetes-associated metabolic disturbances (IR, subclinical inflammation, dyslipidemia, hyperglycemia, dysregulated production of adipokines, defective incretin and gut hormones production/action, and oxidative stress) and ED, focusing on oxidative stress and endothelial progenitor cells (EPCs). In addition, we re-emphasize that oxidative stress is the final common pathway that transduces signals from other conditions-either directly or indirectly-leading to ED and CVD.
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Affiliation(s)
- Mohamed I Saad
- Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.
- Hudson Institute of Medical Research, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia.
| | - Taha M Abdelkhalek
- Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Moustafa M Saleh
- Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Maher A Kamel
- Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Mina Youssef
- Department of Human Genetics, McGill University, Montreal, QC, Canada
| | - Shady H Tawfik
- Department of Molecular Medicine, University of Padova, Padua, Italy
| | - Helena Dominguez
- Department of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark
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Rong J, Chu M, Xing B, Zhu L, Wang S, Tao T, Zhao Y, Jiang L. Variations in the PBEF1 gene are associated with body mass index: A population-based study in northern China. Meta Gene 2015; 6:65-68. [PMID: 30941280 PMCID: PMC5963396 DOI: 10.1016/j.mgene.2015.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 08/15/2015] [Accepted: 08/19/2015] [Indexed: 10/27/2022] Open
Abstract
OBJECTIVE PBEF1 and its polymorphisms may be important in the physiopathology of obesity. We hypothesized that polymorphisms in PBEF1 gene may modify body mass index (BMI). METHODS Thus, we systematically screened 4 tagging polymorphisms (rs4730153, rs2058540, rs3801267 and rs16872158) in PBEF1 gene and evaluated the association between the genetic variants and BMI in a population-based study including 442 subjects in northern China. RESULTS We found that the SNP rs3801267 was significantly associated with decreased BMI (P = 0.026 in additive model), while the other 2 SNPs (rs4730153 and rs16872158) showed a borderline significant association with decreased BMI (P = 0.068 and 0.060 in additive models). Combined analysis of these 3 SNPs showed a significant allele-dosage association between the number of variant alleles and decreased BMI (P trend = 0.007). CONCLUSIONS These findings indicate that genetic variants in PBEF1 gene may modify individual BMI in the Chinese population.
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Affiliation(s)
- Jiesheng Rong
- Second Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China
| | - Minjie Chu
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, PR China
| | - Baifen Xing
- Hongqi Community Health Service Center, Xiangfang District, Harbin, Heilongjiang Province, PR China
| | - Lin Zhu
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China
| | - Shengyu Wang
- Second Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China
| | - Tianzun Tao
- Second Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China
| | - Yashuang Zhao
- Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China
| | - Liying Jiang
- Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, PR China
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Chakraborti CK. Role of adiponectin and some other factors linking type 2 diabetes mellitus and obesity. World J Diabetes 2015; 6:1296-1308. [PMID: 26557957 PMCID: PMC4635140 DOI: 10.4239/wjd.v6.i15.1296] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Revised: 09/14/2015] [Accepted: 10/27/2015] [Indexed: 02/05/2023] Open
Abstract
Because of the intimate association of obesity with type 2 diabetes mellitus (T2DM), during the last two decades, extensive research work is being conducted to find out whether the coexistence of the two is a simple association or there is a positive correlating link between the two. In this article, an attempt has been made to collect and analyse the recent developments in this field and to arrive at a conclusion on the subject. The possible role of several important factors (obtained from adipocytes/not of adipocyte origin) in linking the two has been discussed in detail. Some of the agents, specifically adiponectin, are beneficial (i.e., reduce the incidence of both), while others are harmful (i.e., increase their incidence). From the analysis, it appears that obesity and T2DM are intimately linked.
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Shen CJ, Wang SH, Lee CH, Chan TF. Breastfeeding effects on visfatin levels in postpartum women. Taiwan J Obstet Gynecol 2015; 54:217-20. [DOI: 10.1016/j.tjog.2013.06.019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/04/2013] [Indexed: 02/07/2023] Open
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Kraemer RR, Castracane VD. Endocrine alterations from concentric vs. eccentric muscle actions: a brief review. Metabolism 2015; 64:190-201. [PMID: 25467839 DOI: 10.1016/j.metabol.2014.10.024] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Revised: 10/22/2014] [Accepted: 10/23/2014] [Indexed: 12/31/2022]
Abstract
Resistance exercise has a positive effect on many tissues, including heart, bone, skeletal muscle, and nervous tissue. Eccentric muscle actions offer a unique and a potentially beneficial form of exercise for maintaining and improving health. During resistance exercise, the effects of gravity, and mechanical properties of the sarcomere and connective tissue in skeletal muscle allow a greater muscle load during an eccentric (lengthening) muscle contraction than a concentric (shortening) muscle contraction. Consequently, older patients, patients with muscle or limb movement limitations or injuries, as well as cancer patients may be able to benefit from isolated eccentric muscle actions. There are specific physiological responses to eccentric muscle contractions. This review will describe the effects of different eccentric muscle contraction protocols on endocrine responses that could have positive effects on different tissues and recommend direction for future research.
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Affiliation(s)
- Robert R Kraemer
- Deparment of Kinesiology and Health Studies, Southeastern Louisiana University, Hammond, LA, 70402.
| | - V Daniel Castracane
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, 701 W. 5th St. Odessa, TX, 79763
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Olszanecka-Glinianowicz M, Owczarek A, Bożentowicz-Wikarek M, Brzozowska A, Mossakowska M, Zdrojewski T, Grodzicki T, Więcek A, Chudek J. Relationship between circulating visfatin/NAMPT, nutritional status and insulin resistance in an elderly population - results from the PolSenior substudy. Metabolism 2014; 63:1409-1418. [PMID: 25172122 DOI: 10.1016/j.metabol.2014.07.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Revised: 07/07/2014] [Accepted: 07/29/2014] [Indexed: 12/22/2022]
Abstract
BACKGROUND Circulating visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) levels according to some studies are related to nutritional status and insulin resistance. These associations have not been studied in large elderly populations. Therefore, the aim of our study was to assess the relationships between circulating visfatin/NAMPT levels, nutritional status, and insulin resistance in a large population of the elderly. MATERIALS AND METHODS Concentrations of glucose, albumin, creatinine, CRP, interleukin-6, insulin, and visfatin/NAMPT (by ELISA) were assessed, and HOMA-IR calculated in 3050 elderly participants of the PolSenior study. RESULTS The highest plasma visfatin/NAMPT levels were observed in obese, as well as in non-diabetic insulin resistant subjects; however there were only significant differences found in women. The regression models showed that plasma visfatin/NAMPT levels decline with age and increased with waist circumference, BMI, and hs-CRP. Waist circumference was better correlated than BMI for visfatin/NAMPT levels in statistical models not adjusted by sex, and just the opposite in models which were. We demonstrated a 0.023ng/mL increase of Visfatin/NAMPT levels for 1mg/L increase of hs-CRP, and a 0.007ng/mL decline for each year of age. CONCLUSION Our study revealed that in elderly subjects, circulating visfatin/NAMPT levels are related to age, nutritional status, especially visceral obesity, and inflammation.
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Affiliation(s)
- Magdalena Olszanecka-Glinianowicz
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Faculty of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
| | - Aleksander Owczarek
- Division of Statistics, Department of Instrumental Analysis, Faculty of Pharmacy and Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland
| | - Maria Bożentowicz-Wikarek
- Pathophysiology Unit, Department of Pathophysiology, Faculty of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Aniceta Brzozowska
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Faculty of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | | | - Tomasz Zdrojewski
- Department of Arterial Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland
| | - Tomasz Grodzicki
- Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow, Poland
| | - Andrzej Więcek
- Department of Nephrology, Endocrinology and Metabolic Diseases, Faculty of Medicine in Katowice Medical University of Silesia, Katowice, Poland
| | - Jerzy Chudek
- Pathophysiology Unit, Department of Pathophysiology, Faculty of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; Department of Nephrology, Endocrinology and Metabolic Diseases, Faculty of Medicine in Katowice Medical University of Silesia, Katowice, Poland
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Özcan E, Saygun NI, Serdar MA, Kurt N. Evaluation of the salivary levels of visfatin, chemerin, and progranulin in periodontal inflammation. Clin Oral Investig 2014; 19:921-8. [DOI: 10.1007/s00784-014-1308-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Accepted: 08/17/2014] [Indexed: 12/11/2022]
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Gouranton E, Romier B, Marcotorchino J, Tourniaire F, Astier J, Peiretti F, Landrier JF. Visfatin is involved in TNFα-mediated insulin resistance via an NAD(+)/Sirt1/PTP1B pathway in 3T3-L1 adipocytes. Adipocyte 2014; 3:180-9. [PMID: 25068084 PMCID: PMC4110094 DOI: 10.4161/adip.28729] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 03/21/2014] [Accepted: 03/31/2014] [Indexed: 12/11/2022] Open
Abstract
Tumor necrosis factor α (TNFα) is a well-known mediator of inflammation in the context of obesity in adipose tissue. Its action appears to be directly linked to perturbations of the insulin pathway, leading to the development of insulin resistance. Visfatin has been suspected to be linked to insulin sensitivity, but the mechanism involved is still partly unknown. The aim of this study was to evaluate the role of visfatin in the impairment of the insulin pathway by TNFα activity in 3T3-L1 adipocytes and to unveil the mechanisms involved in such impairment.
We demonstrated in 3T3-L1 adipocytes that visfatin was involved in TNFα-mediated insulin resistance in adipocytes. Indeed, after TNFα treatment in 3T3-L1 cells, visfatin was downregulated, leading to decreased nicotinamide adenine dinucleotide (NAD+) concentrations in cells. This decrease was followed by a decrease in Sirt1 activity, which was linked to an increase in PTP1B expression. The modulation of PTP1B by visfatin was likely responsible for the observed decreases in glucose uptake and Akt phosphorylation in 3T3-L1 adipocytes.
Here, we demonstrated a complete pathway involving visfatin, NAD+, Sirt1, and PTP1B that led to the perturbation of insulin signaling by TNFα in 3T3-L1 adipocytes.
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Tsouma I, Kouskouni E, Demeridou S, Boutsikou M, Hassiakos D, Chasiakou A, Hassiakou S, Baka S. Correlation of visfatin levels and lipoprotein lipid profiles in women with polycystic ovary syndrome undergoing ovarian stimulation. Gynecol Endocrinol 2014; 30:516-9. [PMID: 24576225 DOI: 10.3109/09513590.2014.896896] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The aim of this study was to determine serum and follicular fluid (FF) visfatin levels in age and weight-matched women with polycystic ovary syndrome (PCOS) and normally ovulating subjects undergoing controlled ovarian stimulation and correlate them with their lipid and lipoprotein levels. We included 80 PCOS women (40 lean and 40 overweight) and 80 age- and weight-matched controls, enrolled in the IVF program. In PCOS women, we determined significantly increased serum and FF visfatin as well as serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B, lipoprotein(a) and homocysteine, while high-density lipoprotein cholesterol and apolipoprotein A1 were significantly lower compared to controls. Serum visfatin levels positively correlated with total cholesterol, LDL cholesterol, triglycerides, lipoprotein(a) and homocysteine levels and negatively with apolipoprotein A1. FF visfatin levels positively correlated with triglycerides and homocysteine and negatively with apolipoprotein A1. Dyslipidemia is common in reproductive age women with PCOS exposing them to risk for cardiovascular diseases. However, the detailed role of visfatin on lipoprotein lipid profile awaits further clarification through future investigation.
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Farshchian F, Ramezani Tehrani F, Amirrasouli H, Rahimi Pour H, Hedayati M, Kazerouni F, Soltani A. Visfatin and resistin serum levels in normal-weight and obese women with polycystic ovary syndrome. Int J Endocrinol Metab 2014; 12:e15503. [PMID: 25237319 PMCID: PMC4166205 DOI: 10.5812/ijem.15503] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2013] [Revised: 05/03/2014] [Accepted: 05/19/2014] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of reproductive age that is linked to insulin resistance and obesity. While studies have shown that plasma levels of resistin and visfatin increase with obesity, the association between PCOS and these markers has not been described well. OBJECTIVES This case-control study aimed to compare the serum levels of visfatin and resistin in women with PCOS in comparison with the healthy controls matched for age and body mass index (BMI). PATIENTS AND METHODS A total of 80 women consisted of 40 women with PCOS and 40 matched eumenorrheic women without hyperandrogenism enrolled in the study. They were subcategorized into obese and normal-weight women according to their BMI. Serum visfatin and resistin levels were assessed using sandwich enzyme-linked Immunosorbent assay (ELISA). RESULTS Serum levels of resistin were higher among both obese and normal-weight women with PCOS in comparison with the controls (2.36 and 1.58 ng/mL in normal-weight women with PCOS and controls, respectively; and 2.10 and 1.91 ng/mL in obese women with PCOS and controls, respectively). Serum visfatin levels was higher in both obese women with PCOS and controls (3.46 and 3.49 ng/mL PCOS and control groups, respectively) in comparison with normal-weight women in both groups (3.16 and 3.15 in PCOS and control groups, respectively); however; there were no statistically significant differences in serum resistin and visfatin levels between PCOS and control groups (P > 0.05). CONCLUSIONS While the expression of visfatin and resistin may be upregulated in women with PCOS, it is not translated at serum level.
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Affiliation(s)
- Fatemeh Farshchian
- Medical Laboratory Technology Department, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Houshang Amirrasouli
- Medical Laboratory Technology Department, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
- Corresponding author: Houshang Amirrasouli, Medical Laboratory Technology Department, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran. Tel:+98-2126850560, Fax: +98-2126850560, E-mail:
| | - Hooman Rahimi Pour
- Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Mehdi Hedayati
- Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Faranak Kazerouni
- Medical Laboratory Technology Department, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Adeleh Soltani
- Medical Laboratory Technology Department, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
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Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 2014; 15:6184-223. [PMID: 24733068 PMCID: PMC4013623 DOI: 10.3390/ijms15046184] [Citation(s) in RCA: 1296] [Impact Index Per Article: 117.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Revised: 03/27/2014] [Accepted: 04/01/2014] [Indexed: 02/06/2023] Open
Abstract
Accumulating evidence indicates that obesity is closely associated with an increased risk of metabolic diseases such as insulin resistance, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease. Obesity results from an imbalance between food intake and energy expenditure, which leads to an excessive accumulation of adipose tissue. Adipose tissue is now recognized not only as a main site of storage of excess energy derived from food intake but also as an endocrine organ. The expansion of adipose tissue produces a number of bioactive substances, known as adipocytokines or adipokines, which trigger chronic low-grade inflammation and interact with a range of processes in many different organs. Although the precise mechanisms are still unclear, dysregulated production or secretion of these adipokines caused by excess adipose tissue and adipose tissue dysfunction can contribute to the development of obesity-related metabolic diseases. In this review, we focus on the role of several adipokines associated with obesity and the potential impact on obesity-related metabolic diseases. Multiple lines evidence provides valuable insights into the roles of adipokines in the development of obesity and its metabolic complications. Further research is still required to fully understand the mechanisms underlying the metabolic actions of a few newly identified adipokines.
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Affiliation(s)
- Un Ju Jung
- Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 Sankyuk Dong Puk-ku, Daegu 702-701, Korea.
| | - Myung-Sook Choi
- Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 Sankyuk Dong Puk-ku, Daegu 702-701, Korea.
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Karbaschian Z, Hosseinzadeh-Attar MJ, Giahi L, Golpaie A, Masoudkabir F, Talebpour M, Kosari F, Karbaschian N, Hoseini M, Mazaherioun M. Portal and systemic levels of visfatin in morbidly obese subjects undergoing bariatric surgery. Endocrine 2013; 44:114-8. [PMID: 23104149 DOI: 10.1007/s12020-012-9821-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2012] [Accepted: 10/12/2012] [Indexed: 01/22/2023]
Abstract
The aim of the present study was to compare the levels of visfatin in portal and systemic circulations and to assess the possible relationship of visfatin with systemic inflammation and insulin resistance in morbidly obese patients undergoing bariatric surgery. A total of 46 morbidly obese patients (BMI = 45.3 ± 5.3 kg/m(2)) undergoing bariatric surgery were included in this study. Blood samplings were performed simultaneously from portal and systemic veins during surgery. Visfatin was measured in both portal and systemic venous samples. Besides, fasting serum levels of insulin, glucose, lipid profile, visfatin, and hs-CRP were determined in systemic venous blood samples. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). Visfatin concentrations were significantly higher in portal vein than systemic veins (11.9 ± 12.1 vs. 5.1 ± 3.3 ng/ml, p < 0.0001). While systemic levels of visfatin were significantly correlated with circulating levels of hs-CRP (r = 0.527, p < 0.0001), there were no significant correlations between portal levels of visfatin with systemic levels of hs-CRP concentrations. Substantially higher levels of visfatin in portal vein than systemic veins provide evidence that visceral adipose tissue is the major secretory source of visfatin in humans. Our findings underscore that visceral adipose tissue is an active endocrine organ that is involved in the complex interrelationship between obesity and pathologic conditions.
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Affiliation(s)
- Zohreh Karbaschian
- Tehran University of Medical Sciences, International Campus, (TUMS, IC), Tehran, Iran
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