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Vachher M, Bansal S, Kumar B, Yadav S, Arora T, Wali NM, Burman A. Contribution of organokines in the development of NAFLD/NASH associated hepatocellular carcinoma. J Cell Biochem 2022; 123:1553-1584. [PMID: 35818831 DOI: 10.1002/jcb.30252] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/17/2022] [Accepted: 03/29/2022] [Indexed: 12/16/2022]
Abstract
Globally the incidence of hepatocellular carcinoma (HCC) is on an upsurge. Evidence is accumulating that liver disorders like nonalcoholic fatty liver disease (NAFLD) and its more progressive form nonalcoholic steatohepatitis (NASH) are associated with increased risk of developing HCC. NAFLD has a prevalence of about 25% and 50%-90% in obese population. With the growing burden of obesity epidemic worldwide, HCC presents a major healthcare burden. While cirrhosis is one of the major risk factors of HCC, available literature suggests that NAFLD/NASH associated HCC also develops in minimum or noncirrhotic livers. Therefore, there is an urgent need to understand the pathogenesis and risk factors associated with NAFLD and NASH related HCC that would help in early diagnosis and favorable prognosis of HCC secondary to NAFLD. Adipokines, hepatokines and myokines are factors secreted by adipocytes, hepatocytes and myocytes, respectively, playing essential roles in cellular homeostasis, energy balance and metabolism with autocrine, paracrine and endocrine effects. In this review, we endeavor to focus on the role of these organokines in the pathogenesis of NAFLD/NASH and its progression to HCC to augment the understanding of the factors stimulating hepatocytes to acquire a malignant phenotype. This shall aid in the development of novel therapeutic strategies and tools for early diagnosis of NAFLD/NASH and HCC.
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Affiliation(s)
- Meenakshi Vachher
- Department of Biochemistry, Institute of Home Economics, University of Delhi, Delhi, India
| | - Savita Bansal
- Department of Biochemistry, Institute of Home Economics, University of Delhi, Delhi, India
| | - Bhupender Kumar
- Department of Biochemistry, Institute of Home Economics, University of Delhi, Delhi, India
| | - Sandeep Yadav
- Department of Biochemistry, Institute of Home Economics, University of Delhi, Delhi, India
| | - Taruna Arora
- Department of Biochemistry, Institute of Home Economics, University of Delhi, Delhi, India
| | - Nalini Moza Wali
- Department of Biochemistry, Institute of Home Economics, University of Delhi, Delhi, India
| | - Archana Burman
- Department of Biochemistry, Institute of Home Economics, University of Delhi, Delhi, India
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Kukla M, Menżyk T, Dembiński M, Winiarski M, Garlicki A, Bociąga-Jasik M, Skonieczna M, Hudy D, Maziarz B, Kusnierz-Cabala B, Skladany L, Grgurevic I, Wójcik-Bugajska M, Grodzicki T, Stygar D, Rogula T. Anti-inflammatory adipokines: chemerin, vaspin, omentin concentrations and SARS-CoV-2 outcomes. Sci Rep 2021; 11:21514. [PMID: 34728695 PMCID: PMC8563971 DOI: 10.1038/s41598-021-00928-w] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 10/11/2021] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml; p < 0.001 and 482.1 vs. 814.3 ng/ml; p = 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity.
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Affiliation(s)
- Michał Kukla
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland.,Department of Endoscopy, University Hospital in Kraków, Cracow, Poland
| | - Tomasz Menżyk
- Department of Internal Medicine, Gastroenterology and Acute Intoxication, Regional Hospital, Tarnów, Poland
| | - Marcin Dembiński
- Department of Endoscopy, University Hospital in Kraków, Cracow, Poland.,2nd Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Marek Winiarski
- Department of Endoscopy, University Hospital in Kraków, Cracow, Poland.,2nd Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Aleksander Garlicki
- Chair of Gastroenterology, Hepatology and Infectious Diseases, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Monika Bociąga-Jasik
- Chair of Gastroenterology, Hepatology and Infectious Diseases, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Magdalena Skonieczna
- Department of Systems Biology and Engineering, Silesian University of Technology, 44-100, Gliwice, Poland.,Biotechnology Centre, Silesian University of Technology, 44-100, Gliwice, Poland
| | - Dorota Hudy
- Department of Systems Biology and Engineering, Silesian University of Technology, 44-100, Gliwice, Poland.,Biotechnology Centre, Silesian University of Technology, 44-100, Gliwice, Poland
| | - Barbara Maziarz
- Chair of Clinical BioChemistry, Department of Diagnostics, Faculty of Medicine, Jagiellonian University Medical College, 31-501, Cracow, Poland
| | - Beata Kusnierz-Cabala
- Chair of Clinical BioChemistry, Department of Diagnostics, Faculty of Medicine, Jagiellonian University Medical College, 31-501, Cracow, Poland
| | - Lubomir Skladany
- Department of Internal Medicine and HEGITO (Hepatology, Gastroenterology and Liver Transplantation), F.D. Roosevelt University Hospital, Banska Bystrica, Slovakia
| | - Ivica Grgurevic
- Zagreb University School of Medicine, Šalata ul. 2, 10000, Zagreb, Croatia.,Division for Liver Diseases, Department of Gastroenterology, Dubrava University Hospital, Zagreb, Croatia
| | - Małgorzata Wójcik-Bugajska
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Tomasz Grodzicki
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Dominika Stygar
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, 40-055, Katowice, Poland.
| | - Tomasz Rogula
- Case Western Reserve University School of Medicine, Cleveland, OH, USA.,1st Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
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Chaudhari R, Fouda S, Sainu A, Pappachan JM. Metabolic complications of hepatitis C virus infection. World J Gastroenterol 2021; 27:1267-1282. [PMID: 33833481 PMCID: PMC8015302 DOI: 10.3748/wjg.v27.i13.1267] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/10/2021] [Accepted: 03/12/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.
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Affiliation(s)
- Rahul Chaudhari
- Department of Medicine, Pennsylvania Hospital of the University of Pennsylvania, Pennsylvania, PA 19104, United States
| | - Sherouk Fouda
- School of Health and Biomedical Sciences, RMIT University, Melbourne VIC 3000, Australia
| | - Ashik Sainu
- Department of Gastroenterology and Hepatology, Aster Oman Hospital, Al Ghubra, Muscat OM 133, Oman
| | - Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
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Serum concentrations of selected adipokines in virus-related liver cirrhosis and hepatocellular carcinoma. Clin Exp Hepatol 2020; 6:235-242. [PMID: 33145430 PMCID: PMC7592085 DOI: 10.5114/ceh.2020.99517] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 05/28/2020] [Indexed: 12/16/2022] Open
Abstract
Aim of the study Hepatotropic viruses cause metabolic disturbances such as insulin resistance and hepatosteatosis. Moreover, metabolic factors, such as insulin resistance, obesity, and type 2 diabetes mellitus, increase the risk for hepatocellular carcinoma (HCC) in patients with virus-related liver cirrhosis. Cytokines secreted by the adipose tissue (adipokines) may be implicated in these metabolic disturbances, but there is little evidence regarding the role of adipokines in virus-related cirrhosis and HCC. Thus, we studied whether serum concentrations of selected adipokines were altered in patients with virus-related liver cirrhosis, including patients with HCC. Material and methods We included 43 patients with liver cirrhosis due to chronic hepatitis B or chronic hepatitis C. Of these patients, 36 had HCC and 7 did not have any malignant lesions. In addition to routine clinical and laboratory variables, we analyzed serum concentrations of betatrophin, insulin, vaspin, visfatin, and irisin. Results Compared with healthy controls, patients with HCC had significantly increased vaspin concentrations and significantly reduced irisin concentrations. Compared with controls, patients with virus-related cirrhosis, with or without HCC, had significantly increased concentrations of insulin and betatrophin. The serum visfatin concentration was non-significantly higher in patients with virus-related cirrhosis than in controls. None of the studied adipokines was a significant predictor of HCC. Serum concentrations of the studied adipokines were not related to cirrhosis severity or HCC stage. Conclusions Metabolic parameters, including serum adipokine concentrations, are altered in patients with virus-related liver cirrhosis. Adipokines might be related to the HCC risk in these patients.
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Pazgan-Simon M, Kukla M, Zuwała-Jagiełło J, Derra A, Bator M, Menżyk T, Lekstan A, Grzebyk E, Simon K. Serum visfatin and vaspin levels in hepatocellular carcinoma (HCC). PLoS One 2020; 15:e0227459. [PMID: 31935230 PMCID: PMC6959555 DOI: 10.1371/journal.pone.0227459] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Accepted: 12/18/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver cancer, accountable for 90% cases. Visfatin and vaspin are adipocytokines with various suggested functions and proven significant correlations between BMI and percentage of body fat. The aim was to assess visfatin and vaspin serum levels in HCC patients and controls, compare their levels in patients with different cancer etiology and grade assessed according to the Barcelona-Clinic Liver Cancer (BCLC) staging system. The additional aim was to analyze relationship between analyzed adipokines and metabolic abnormalities and liver disfunction severity. The study was performed on 69 cirrhotic patients (54 males/15 females) with HCC, aged 59.0 ± 12.1 years, and with BMI 29.0 ± 4.5 kg/m2 compared to 20 healthy volunteers. Serum visfatin and vaspin concentrations were significantly increased in HCC patients compared to controls (p = 0.01 and p = 0.02, respectively). Serum vaspin was significantly higher in HCC patients with viral compared to those with non-viral etiology (p = 0.02), with more evident increase in chronic hepatitis C patients (CHC). Serum visfatin levels were significantly higher in patients with higher insulin resistance (p = 0.04) and with platelets count > 100 000/mm3 (p<0.001). Patients with BMI >30 kg/m2 had markedly up-regulated vaspin levels (p = 0.04). There was no difference in vaspin and visfatin serum levels with respect to liver dysfunction and BCLC classification. In conclusion, our study revealed serum vaspin and visfatin to be significantly increased in HCC patients independently of cancer etiology compared to controls. Additionally, serum vaspin was elevated in viral disease, especially in CHC. Vaspin up-regulation can be a compensatory mechanism against IR in HCC patients. Serum visfatin and vaspin, although up-regulated, seem not to be associated with cancer grade and cirrhosis severity.
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Affiliation(s)
- Monika Pazgan-Simon
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wroclaw, Poland
| | - Michał Kukla
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wroclaw, Poland
- Department of Gastroenterology and Hepatology, Medical University of Silesia in Katowice, Katowice, Poland
- * E-mail:
| | | | | | - Martyna Bator
- Medical University of Silesia in Katowice, Katowice, Poland
| | - Tomasz Menżyk
- Medical University of Silesia in Katowice, Katowice, Poland
| | - Andrzej Lekstan
- Department of Digestive Tract Surgery, Medical University of Silesia in Katowice, Katowice, Poland
| | - Ewa Grzebyk
- Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Wroclaw, Poland
| | - Krzysztof Simon
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Wroclaw, Poland
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Skonieczna M, Hudy D, Hejmo T, Buldak RJ, Adamiec M, Kukla M. The adipokine vaspin reduces apoptosis in human hepatocellular carcinoma (Hep-3B) cells, associated with lower levels of NO and superoxide anion. BMC Pharmacol Toxicol 2019; 20:58. [PMID: 31511067 PMCID: PMC6737690 DOI: 10.1186/s40360-019-0334-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 08/29/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Among adipose-derived factors, adipocytokines play roles as hormones and signaling mediators for apoptotic pathway. Among of them, vaspin, regulates the metabolism of adipose tissue itself as an endocrine organ, and stimulates adipocytes to maturation, differentiation, etc. Damaged adipocytes, present in obesity and hepatocellular carcinoma (HCC) respond with over-production of inflammatory cytokines. Such pro-inflammatory stimulation remains under adipokine control. Pro-inflammatory pathways are connected to oxidative stress and apoptosis, reported as co-existing with an elevated level of some adipokines in cancer cell lines. However, some hormones, such as vaspin, reduce apoptosis, have anti-inflammatory and anti-oxidative roles in cancer cell lines. METHODS Hep-3B cells were cytometrically evaluated under vaspin treatment for reactive oxygen species (ROS) and apoptosiss induction. The statistical significant changes to the untreated controls was calculated by T-tests (indicated at value p < 0.05). RESULTS Here we studied the production of reactive oxygen and nitrogen species in cells of HCC line Hep-3B after vaspin treatment. A decreased level of nitric oxide and superoxide anion 24 h after vaspin addition at 5 ng/ml was correlated with restricted, to the physiological level, apoptosis. A protective role of vaspin was displayed as enhanced cell viability and proliferation, which could be a poor prognostic in liver cancer. CONCLUSIONS Apoptosis was suppressed after vaspin treatment, together with low levels of nitric oxide and superoxide anions.
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Affiliation(s)
- Magdalena Skonieczna
- Systems Engineering Group, Silesian University of Technology, Institute of Automatic Control, 16 Akademicka Street, 44-100 Gliwice, Poland
- Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland
| | - Dorota Hudy
- Systems Engineering Group, Silesian University of Technology, Institute of Automatic Control, 16 Akademicka Street, 44-100 Gliwice, Poland
- Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland
| | - Tomasz Hejmo
- Department of Biochemistry, Medical University of Silesia, School of Medicine with the Division of Dentistry, Jordana 19, 41-808 Zabrze, Poland
| | - Rafal J. Buldak
- Department of Biochemistry, Medical University of Silesia, School of Medicine with the Division of Dentistry, Jordana 19, 41-808 Zabrze, Poland
| | - Małgorzata Adamiec
- Systems Engineering Group, Silesian University of Technology, Institute of Automatic Control, 16 Akademicka Street, 44-100 Gliwice, Poland
- Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland
| | - Michal Kukla
- Department of Gastroenterology and Hepatology, School of Medicine in Katowice, Medical University of Silesia, Medyków 14, 40-752 Katowice, Poland
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Ali S, Ellakwa D, Emara S, El-Sabbagh N. The role of chemerin and vaspin in Egyptian patients with viral hepatitis C. Meta Gene 2018. [DOI: 10.1016/j.mgene.2018.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Wang Q, Xi W, Yin L, Wang J, Shen H, Gao Y, Min J, Zhang Y, Wang Z. Human Epicardial Adipose Tissue cTGF Expression is an Independent Risk Factor for Atrial Fibrillation and Highly Associated with Atrial Fibrosis. Sci Rep 2018; 8:3585. [PMID: 29483593 PMCID: PMC5827202 DOI: 10.1038/s41598-018-21911-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 02/13/2018] [Indexed: 12/19/2022] Open
Abstract
Epicardial adipose tissue (EAT) is associated with the incidence, perpetuation, and recurrence of atrial fibrillation (AF), with elusive underlying mechanisms. We analyzed adipokine expression in samples from 20 patients with sinus rhythm (SR) and 16 with AF. Quantitative real-time PCR showed that connective tissue growth factor (cTGF) expression was significantly higher in EAT than in subcutaneous adipose tissue (SAT) or paracardial adipose tissue (PAT) from patients with AF, and in EAT from patients with SR (P < 0.001). Galectin-3 expression was significantly higher in EAT than in SAT or PAT (P < 0.001), with no significant differences between patients with AF and SR (P > 0.05). Leptin and vaspin expression were lower in EAT than in PAT (P < 0.001). Trichrome staining showed that the fibrosis was much more severe in patients with AF than SR (P < 0.001). We found a linear relationship between cTGF mRNA expression level and collagen volume fraction (y = 1.471x + 27.330, P < 0.001), and logistic regression showed that cTGF level was an independent risk factor for AF (OR 2.369, P = 0.027). In conclusion, highly expressed in EAT, cTGF is associated with atrial fibrosis, and can be an important risk factor for AF.
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Affiliation(s)
- Qing Wang
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wang Xi
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Liang Yin
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jing Wang
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Hua Shen
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yang Gao
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jie Min
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yufeng Zhang
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
| | - Zhinong Wang
- Center for Comprehensive Treatment of Atrial Fibrillation, Department of Cardiothoracic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
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Vaspin regulates the osteogenic differentiation of MC3T3-E1 through the PI3K-Akt/miR-34c loop. Sci Rep 2016; 6:25578. [PMID: 27156573 PMCID: PMC4860647 DOI: 10.1038/srep25578] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Accepted: 04/18/2016] [Indexed: 01/15/2023] Open
Abstract
Vaspin (visceral adipose tissue-derived serine protease inhibitor) is a newly discovered adipokine that widely participates in diabetes mellitus, polycystic ovarian syndrome and other disorders of metabolism. However, the effect of vaspin on the regulation of osteogenesis and the mechanism responsible are still unclear. Here, we found that vaspin can attenuate the osteogenic differentiation of the preosteoblast cell line MC3T3-E1 in a dose-dependent way; also, during this process, the expression of miRNA-34c (miR-34c) was significantly increased. Down-regulation of the expression of miR-34c in MC3T3-E1 diminished the osteogenic inhibitory effect of vaspin, while the up-regulation of miR-34c increased this effect through its target gene Runx2. Meanwhile, we found that vaspin could also activate the PI3K-Akt signalling pathway. Blocking the PI3K-Akt signalling pathway with specific inhibitors could decrease the osteogenic inhibitory effect of vaspin as well as the expression level of miR-34c. Furthermore, knock-down of miR-34c could promote the activation of Akt, which was probably realised by targeting c-met expression. Thus, PI3K-Akt and miR-34c constituted a modulation loop and controlled the expression of each other. Taken together, our study showed that vaspin could inhibit the osteogenic differentiation in vitro, and the PI3K-Akt/miR-34c loop might be the underlying mechanism.
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Kukla M, Piotrowski D, Waluga M, Hartleb M. Insulin resistance and its consequences in chronic hepatitis C. Clin Exp Hepatol 2015; 1:17-29. [PMID: 28856251 PMCID: PMC5421163 DOI: 10.5114/ceh.2015.51375] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2015] [Accepted: 03/10/2015] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis C (CHC) is generally a slowly progressive disease, but some factors associated with rapid progression have been identified. Hepatitis C virus (HCV) may contribute to a broad spectrum of metabolic disturbances - namely, steatosis, insulin resistance (IR), increased prevalence of impaired glucose tolerance, type 2 diabetes mellitus (T2DM), lipid metabolism abnormalities and atherosclerosis. HCV can directly or indirectly cause both IR and steatosis, but it is still not resolved whether this viral impact bears the same prognostic value as the metabolic counterparts. As the population exposed to HCV ages, the morbidity due to this disease is increasing. The rising epidemic of obesity contributes to higher prevalence of IR and T2DM. Our understanding of the mutual association between both disease states continues to grow, but is still far from complete. This review briefly discusses the most probable mechanisms involved in IR development in the course of CHC. Molecular mechanisms for the direct and indirect influence of HCV on intracellular insulin signaling are described. Subsequently, the consequences of IR/T2DM for disease progression and management are summarized.
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Affiliation(s)
- Michał Kukla
- Department of Gastroenterology and Hepatology, Medical University of Silesia in Katowice, Poland
| | - Damian Piotrowski
- Department of Infectious Diseases in Bytom, Medical University of Silesia in Katowice, Poland
| | - Marek Waluga
- Department of Gastroenterology and Hepatology, Medical University of Silesia in Katowice, Poland
| | - Marek Hartleb
- Department of Gastroenterology and Hepatology, Medical University of Silesia in Katowice, Poland
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Long-term Effect of Ileal Transposition on Adipokine Serum Level in Zucker (Orl)-Lepr fa Fatty Rats. Obes Surg 2015; 25:1848-57. [DOI: 10.1007/s11695-015-1618-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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