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Tasli NG, Gunay BO, Ugurlu A, Eren MA, Aykut M, Esenülkü CM. Optical coherence tomography angiography in non-alcoholic fatty liver disease: is it a disease affecting the microvascular system?? BMC Ophthalmol 2025; 25:311. [PMID: 40410774 PMCID: PMC12102921 DOI: 10.1186/s12886-025-04136-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Accepted: 05/13/2025] [Indexed: 05/25/2025] Open
Abstract
PURPOSE To investigate retinal thickness and vascular structure in patients with non-alcoholic fatty liver disease (NAFLD) using optical coherence tomography (OCT) and OCT angiography (OCTA) and to compare the results with healthy controls. METHOD The medical records of NAFLD patients were retrospectively reviewed. Macular thickness (MT) and peripapillary retinal nerve fibre layer (pRNFL) thickness were assessed. The vessel density (VD) of Superficial Capillary Plexus (SCP), Deep Capillary Plexus (DCP), foveal avascular zone (FAZ) area, FAZ circularity index (CI), and FAZ perimeter were also recorded. RESULTS The study included 64 patients with NAFLD and 64 healthy controls. Mean MT and pRNFLT were similar between groups. The study group showed a significant reduction in VD-DCP compared to the control group (36.0 ± 5.2 vs. 38.5 ± 4.1, p < 0.001). Total FAZ area was greater in the study group than in the control group (0.42 ± 0.10 vs. 0.33 ± 0.12mm2, p < 0.001). FAZ CI also differed between groups (0.47 ± 0.08 vs. 0.53 ± 0.08, p < 0.001). Enlarged FAZ area and decreased VD-DCP were significantly associated with NAFLD severity. CONCLUSION Individuals with NAFLD have certain changes in the retinal microvasculature, including reduced VD-DCP, an increased FAZ area, and a decreased of FAZ CI. The variations in VD-DCP and FAZ area exhibit discrepancies according to the disease grade. There are some limitations, including its retrospective nature, the small number of participants, the lack of analysis of the peripapillary area, and the lack of examination of longitudinal changes.
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Affiliation(s)
- Nurdan Gamze Tasli
- Department of Ophthalmology, University of Health Sciences, Trabzon Kanuni Training and Resarch Hospital, Trabzon, Turkey.
| | - Betul Onal Gunay
- Department of Ophthalmology, University of Health Sciences, Trabzon Kanuni Training and Resarch Hospital, Trabzon, Turkey
| | - Adem Ugurlu
- Department of Ophthalmology, College of Medicine, Erzincan Binali Yıldırım University Hospital, Erzincan, Turkey
| | - Mehtap Arslanturk Eren
- Department of Ophthalmology, University of Health Sciences, Trabzon Kanuni Training and Resarch Hospital, Trabzon, Turkey
| | - Murat Aykut
- Department of Ophthalmology, University of Health Sciences, Trabzon Kanuni Training and Resarch Hospital, Trabzon, Turkey
| | - Cenap Mahmut Esenülkü
- Department of Ophthalmology, University of Health Sciences, Trabzon Kanuni Training and Resarch Hospital, Trabzon, Turkey
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Zhu Y, Ke Y, Hu Y, Wu K, Liu S, Hu J. Association of circulating vaspin levels and patients with metabolic-associated fatty liver disease: a systematic review and meta-analysis. Lipids Health Dis 2022; 21:57. [PMID: 35780150 PMCID: PMC9250748 DOI: 10.1186/s12944-022-01658-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 05/24/2022] [Indexed: 11/14/2022] Open
Abstract
Background The incidence rate of metabolic-associated fatty liver disease (MAFLD) is increasing annually; however, there are still no effective methods for establishing an early diagnosis and conducting real-time tracing. Vaspin can affect the metabolic processes in the body, and it is closely associated with many metabolic diseases. Many previous studies have speculated on the association between vaspin and MAFLD, but the results of these studies have not been conclusive. This meta-analysis examined the differences in circulating vaspin levels between patients with MAFLD and healthy individuals. Methods Six databases and other sources were searched with free terms and Medical Subject Headings terms, and a total of 13 articles were included (900 cases and 669 controls). RevMan 5.3 and Stata 16 were used for analysis. The standardised mean difference (SMD) and 95% confidence interval (CI) were used to assess the overall outcomes. Cohen’s kappa coefficient was applied to examine the differences between the two authors in the selection of studies and in the evaluation of the quality of evidence for the studies. Results The results demonstrated that there was no significant difference in the circulating vaspin levels between the MAFLD group and healthy group (SMD = 0.46, 95% CI: [− 0.12, 1.04]). The subgroup analysis suggested that area and body mass index (BMI) may be the sources of heterogeneity, and the results of univariate meta-regression analysis were consistent with those of the subgroup analysis (P = 0.005 and P < 0.001, respectively). Furthermore, BMI may better explain the source of heterogeneity (P = 0.032) in the multivariate meta-regression analysis. Conclusion In summary, no significant correlation was observed between the circulating vaspin levels and MAFLD. BMI may be an important factor affecting this correlation, which may provide a reference for further studies on mechanism and diagnosis of MAFLD. Supplementary Information The online version contains supplementary material available at 10.1186/s12944-022-01658-2.
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Affiliation(s)
- Yuqing Zhu
- The First Clinical Medical College of Zhejiang Chinese Medical University, No 548, Binwen Road, Hangzhou, 310051, Zhejiang Province, China
| | - Yani Ke
- The Second Clinical Medical College of Zhejiang Chinese Medical University, No 548, Binwen Road, Hangzhou, 310051, Zhejiang Province, China
| | - Yijie Hu
- The Third Clinical Medical College of Zhejiang Chinese Medical University, No 548, Binwen Road, Hangzhou, 310051, Zhejiang Province, China
| | - Kaihan Wu
- The First Clinical Medical College of Zhejiang Chinese Medical University, No 548, Binwen Road, Hangzhou, 310051, Zhejiang Province, China
| | - Shan Liu
- Department of Clinical Evaluation Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, Hangzhou, 310006, Zhejiang Province, China.
| | - Jie Hu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, Hangzhou, 310006, Zhejiang Province, China.
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Tumkosit M, Han WM, Tankittiwat K, Chattranukulchai P, Siwamogsatham S, Apornpong T, Ureaphongsukkit T, Kerr SJ, Boonyaratavej S, Avihingsanon A. Higher epicardial fat in older adults living with HIV with viral suppression and relationship with liver steatosis, coronary calcium and cardiometabolic risks. AIDS 2022; 36:1073-1081. [PMID: 35212667 DOI: 10.1097/qad.0000000000003204] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES HIV infection is associated with ectopic fat deposition, which leads to chronic inflammation and cardiometabolic dysregulation. We assessed the epicardial adipose tissue (EAT) volume and its associated factors among people with HIV (PWH). DESIGN A cross-sectional study. METHODS We conducted a cross-sectional study among PWH aged at least 50 years and age-matched and sex-matched HIV-negative older individuals in Bangkok, Thailand. Participants underwent a noncontrast, cardiac computed tomography (CT) scan to assess coronary artery calcium (CAC) score and EAT between March 2016 and June 2017. Multivariate linear regression analyses were used to investigate HIV-related factors, cardiac and metabolic markers associated with EAT volume. RESULTS Median age was 55 years [interquartile range (IQR) 52-60] and 63% were men. Median duration of antiretroviral therapy (ART) was 16 years with 97% had HIV-1 RNA less than 50 copies/ml and median CD4 + cell count of 617 cells/μl. Median EAT volume was significantly higher in PWH [99 (IQR 75-122) cm 3 ] than HIV-negative individuals [93 (IQR 69-117) cm 3 ], P = 0.022. In adjusted model, factors associated with EAT volume included male sex ( P = 0.045), older age ( P < 0.001), abnormal waist circumference ( P < 0.001) and HOMA-IR ( P = 0.01). In addition, higher CAC score was independently associated with EAT volume. Higher mean EAT volume was seen in PWH with severe liver steatosis than those without steatosis ( P = 0.018). In adjusted PWH-only model, duration of HIV was significantly associated with higher EAT volume ( P = 0.028). CONCLUSION In an aging cohort, PWH had higher EAT volume than HIV-negative controls. EAT was also independently associated with central fat accumulation, insulin resistance, liver steatosis and CAC score.
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Affiliation(s)
- Monravee Tumkosit
- Department of Radiology, Faculty of Medicine, Chulalongkorn University
| | - Win Min Han
- HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
- The Kirby Institute, University of New South Wales, Sydney, Australia
- Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | | | | | | | | | - Stephen J Kerr
- HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
- The Kirby Institute, University of New South Wales, Sydney, Australia
- Biostatistics Excellence Centre
| | | | - Anchalee Avihingsanon
- HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
- Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Yong JN, Ng CH, Lee CWM, Chan YY, Tang ASP, Teng M, Tan DJH, Lim WH, Quek J, Xiao J, Chin YH, Foo R, Chan M, Lin W, Noureddin M, Siddiqui MS, Muthiah MD, Sanyal A, Chew NWS. Non-alcoholic fatty liver disease association with structural heart, systolic and diastolic dysfunction: a meta-analysis. Hepatol Int 2022; 16:269-281. [PMID: 35320497 DOI: 10.1007/s12072-022-10319-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 02/11/2022] [Indexed: 01/30/2023]
Abstract
OBJECTIVE Several studies have documented a relationship between non-alcoholic fatty liver disease (NAFLD) and structural heart disease, particularly diastolic function. This meta-analysis will be the first to examine the echocardiographic-derived cardiac function and structural characteristics in NAFLD patients, and its association with liver disease severity and metabolic profile. METHODS Medline and Embase were searched and pairwise meta-analysis was conducted in DerSimonian and Laird to obtain the odds ratio (OR) and mean difference (MD) for dichotomous and continuous variables, respectively, to compare the effects of NAFLD on the echocardiography parameters. RESULTS Forty-one articles involving 33,891 patients underwent echocardiography. NAFLD patients had worse systolic indices with lower ejection fraction (EF, MD: - 0.693; 95% CI: - 1.112 to - 0.274; p = 0.001), and worse diastolic indices with higher E/e' (MD: 1.575; 95% CI: 0.924 to 2.227; p < 0.001) compared to non-NAFLD patients. NAFLD patients displayed increased left ventricular mass (LVM, MD: 34.484; 95% CI: 26.236 to 42.732; p < 0.001) and epicardial adipose thickness (EAT, MD: 0.1343; 95% CI: 0.055 to 0.214; p = 0.001). An increased severity of NAFLD was associated with worse diastolic indices (decreased E/A ratio, p = 0.007), but not with systolic indices. CONCLUSIONS NAFLD is associated with impaired systolic and diastolic function with changes in cardiac structure. Concomitant metabolic risk factors and liver disease severity are independently associated with worsening systolic and diastolic function.
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Affiliation(s)
- Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chloe Wen-Min Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yu Yi Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ansel Shao Pin Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Margaret Teng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yip Han Chin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Roger Foo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Department of Cardiology, National University Heart Centre, National University Hospital, Tower Block Level 9, 1E Kent Ridge Road, Singapore, 119228, Singapore
| | - Mark Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Department of Cardiology, National University Heart Centre, National University Hospital, Tower Block Level 9, 1E Kent Ridge Road, Singapore, 119228, Singapore
| | - Weiqin Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Department of Cardiology, National University Heart Centre, National University Hospital, Tower Block Level 9, 1E Kent Ridge Road, Singapore, 119228, Singapore
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Comprehensive Transplant Center, Los Angeles, CA, USA
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. .,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore. .,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.
| | - Arun Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Nicholas W S Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. .,Department of Cardiology, National University Heart Centre, National University Hospital, Tower Block Level 9, 1E Kent Ridge Road, Singapore, 119228, Singapore.
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Özkan EA, Sadigov A, Öztürk O. Evaluation of Serum Omentin-1, Vaspin, Leptin, Adiponectin Levels in Obese/Overweight Children and Their Relationship With Non-Alcoholic Fatty Liver Disease. Clin Nutr Res 2022; 11:194-203. [PMID: 35949560 PMCID: PMC9348910 DOI: 10.7762/cnr.2022.11.3.194] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/06/2022] [Accepted: 07/11/2022] [Indexed: 11/26/2022] Open
Abstract
To investigate adipokines (vaspin, omentin-1, adiponectin and leptin) and their correlation with hepatosteatosis degree in obese/overweight (O/O) children. We analyzed adipokine levels of 81 children (49 O/O, [body mass index (BMI) > 95th] and 32 non-obese (BMI = 5-85th) admitted to the pediatric outpatient clinic. Serum triglyceride, glucose, low density lipoprotein-cholesterol, total cholesterol, high density lipoprotein-cholesterol, alanine aminotransferase, aspartate aminotransferase (AST), insulin, HbA1c levels and leptin, omentin-1, vaspin, adiponectin levels were studied. O/O children with hepatosteatosis were divided into grades 1, 2 and 3 according to the degree of hepatosteatosis determined by ultrasonography. While AST (p = 0.001), triglyceride (p = 0.006), BMI percentile (p = 0.000), HOMA index (p = 0.002), systolic blood pressure (p = 0.02), leptin (p = 0.001), omentin-1 (p = 0.001), adiponectin (p = 0.001) levels were higher, vaspin level was lower (p = 0.008) in the (O/O) group compared to the controls. There was a positive correlation between HDL and vaspin, and a negative correlation between HDL and omentin-1 in the O/O group. Also it was observed that as the degree of hepatosteotosis increased, leptin (p = 0.004), omentin-1 (p = 0.001) levels were increased. There was no significant change in vaspin level (p = 0.128). The high levels of omentin-1, leptin and adiponectin have an association with the development of hepatosteatosis in O/O children.
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Affiliation(s)
- Esra Akyüz Özkan
- Ondokuz Mayıs University Medical Faculty, Department of Pediatrics, Samsun 55139, Turkey
| | - Allahverdi Sadigov
- Yozgat Bozok University Medical Faculty, Department of Pediatrics, Yozgat 66200, Turkey
| | - Osman Öztürk
- Yozgat Bozok University Medical Faculty, Department of Pediatrics, Yozgat 66200, Turkey
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Emamat H, Tangestani H, Behrad Nasab M, Ghalandari H, Hekmatdoost A. The association between epicardial adipose tissue and non-alcoholic fatty liver disease: A systematic review of existing human studies. EXCLI JOURNAL 2021; 20:1096-1105. [PMID: 34345229 PMCID: PMC8326500 DOI: 10.17179/excli2021-3815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 06/10/2021] [Indexed: 11/24/2022]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) has significantly risen all around the world. Although visceral fat mass has been identified as an independent risk factor for NAFLD, the association of other ectopic fat depots, such as Epicardial adipose tissue (EAT), with the disease has not been fully elucidated. The aim of the current study was to systematically review all available human studies conducted on the associations between EAT and NAFLD. All human studies published in English, which examined the association between the thickness or the volume of EAT and the incidence of NAFLD were systematically searched on PubMed, Scopus, and Google Scholar search engines, from inception up to April 2021. Eighteen studies that met inclusion criteria were included in the final review. A total of 86 studies were found through searching the databases. After excluding duplicates, seventy six remained studies were scanned by title and abstract, out of which, 58 were excluded. Finally, eighteen articles (thirteen cross-sectional studies and five case-control studies) published between 2008 and 2021, were included in the review. According to the results of the reviewed articles, EAT was associated with the presence and progression of NAFLD. Furthermore, NAFLD patients with thicker EAT may need a more intensive hepatic follow-up. However, we suggest further investigation to find out the underlying mechanisms describing the observed association.
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Affiliation(s)
- Hadi Emamat
- Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hadith Tangestani
- Department of Nutrition, Faculty of Health and Nutrition, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Mojgan Behrad Nasab
- Nutritionist, Emam Reza Hospital, AJA University of Medical Sciences, Tehran, Iran
| | - Hamid Ghalandari
- Department of Clinical Nutrition, Faculty of Nutrition and Food Sciences, Shiraz University of Medical Sciences
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Jichitu A, Bungau S, Stanescu AMA, Vesa CM, Toma MM, Bustea C, Iurciuc S, Rus M, Bacalbasa N, Diaconu CC. Non-Alcoholic Fatty Liver Disease and Cardiovascular Comorbidities: Pathophysiological Links, Diagnosis, and Therapeutic Management. Diagnostics (Basel) 2021; 11:689. [PMID: 33921359 PMCID: PMC8069361 DOI: 10.3390/diagnostics11040689] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/09/2021] [Accepted: 04/11/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has a growing prevalence in recent years. Its association with cardiovascular disease has been intensively studied, and certain correlations have been identified. The connection between these two entities has lately aroused interest regarding therapeutic management. In order to find the best therapeutic options, a detailed understanding of the pathophysiology that links (NAFLD) to cardiovascular comorbidities is needed. This review focuses on the pathogenic mechanisms that are behind these two diseases and on the therapeutic management available at this time.
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Affiliation(s)
- Alexandra Jichitu
- Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania; (A.J.); (C.C.D.)
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
| | - Ana Maria Alexandra Stanescu
- Department 5, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Cosmin Mihai Vesa
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (C.M.V.); (C.B.)
| | - Mirela Marioara Toma
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
| | - Cristiana Bustea
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (C.M.V.); (C.B.)
| | - Stela Iurciuc
- Department of Cardiology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Marius Rus
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania;
| | - Nicolae Bacalbasa
- Department 13, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Department of Surgery, “Ion Cantacuzino” Clinical Hospital, 030167 Bucharest, Romania
| | - Camelia Cristina Diaconu
- Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania; (A.J.); (C.C.D.)
- Department 5, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
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Oikonomidou AC, Doundoulakis I, Antza C, Kalopitas G, Dardavessis T, Chourdakis M. Evaluation of subclinical cardiac damage in biopsy-proven nonalcoholic fatty liver disease: a systematic review and meta-analysis. Ann Gastroenterol 2021; 34:424-430. [PMID: 33948069 PMCID: PMC8079885 DOI: 10.20524/aog.2021.0594] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 10/20/2020] [Indexed: 12/11/2022] Open
Abstract
Background Data on the association of nonalcoholic fatty liver disease (NAFLD) with subclinical cardiac damage are scanty. We performed a systematic review to provide comprehensive information on subclinical cardiac alterations among NAFLD subjects. Methods PubMed and the Cochrane Library were searched to identify studies comparing subclinical cardiac damage between NAFLD and healthy adults. We also searched PROSPERO to check for any similar meta-analysis in progress in order to avoid duplication with our study. Conference abstracts and the reference lists of relevant studies and systematic reviews were perused. The Newcastle-Ottawa quality assessment scale for case-control and cohort studies were used to assess study quality. Results Seven studies were finally included in the meta-analysis (1 cross sectional and 6 case-control), with a total of 602 individuals (362 patients with NAFLD). Epicardial fat thickness were statistically significantly higher in patients with NAFLD than in controls (mean difference [MD] 1.17, 95% confidence interval [CI] 0.45-1.89, I2=89%). Global longitudinal strain was lower in NAFLD, to a statistically significant degree (MD -3.17, 95%CI -5.09 to -1.24, I2=89%). However, significant heterogeneity of the findings was observed. Conclusions Our findings indicate that NAFLD is related to subclinical cardiac damage. Further studies with a larger number of biopsy-proven NAFLD patients are needed to confirm this finding. Preventive and therapeutic interventions early in the course of the disease might decrease morbidity in this high-risk patient group.
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Affiliation(s)
- Artemis Christina Oikonomidou
- Department of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki (Artemis Christina Oikonomidou, Ioannis Doundoulakis, Theodoros Dardavessis, Michail Chourdakis)
| | - Ioannis Doundoulakis
- Department of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki (Artemis Christina Oikonomidou, Ioannis Doundoulakis, Theodoros Dardavessis, Michail Chourdakis).,Department of Cardiology, 424 General Military Training Hospital, Thessaloniki (Ioannis Doundoulakis)
| | - Christina Antza
- 3 Department of Internal Medicine, G.H. "Papageorgiou", School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki (Christina Antza)
| | - Georgios Kalopitas
- Division of Gastroenterology and Hepatology, 1 Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki (Georgios Kalopitas), Greece
| | - Theodoros Dardavessis
- Department of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki (Artemis Christina Oikonomidou, Ioannis Doundoulakis, Theodoros Dardavessis, Michail Chourdakis)
| | - Michail Chourdakis
- Department of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki (Artemis Christina Oikonomidou, Ioannis Doundoulakis, Theodoros Dardavessis, Michail Chourdakis)
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9
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Kang GJ, Kim EJ, Lee CH. Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators on Cardiac Fibrosis via NRF2 Activation. Antioxidants (Basel) 2020; 9:antiox9121259. [PMID: 33321955 PMCID: PMC7764646 DOI: 10.3390/antiox9121259] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/09/2020] [Accepted: 12/09/2020] [Indexed: 12/19/2022] Open
Abstract
Heart disease is the number one mortality disease in the world. In particular, cardiac fibrosis is considered as a major factor causing myocardial infarction and heart failure. In particular, oxidative stress is a major cause of heart fibrosis. In order to control such oxidative stress, the importance of nuclear factor erythropoietin 2 related factor 2 (NRF2) has recently been highlighted. In this review, we will discuss the activation of NRF2 by docosahexanoic acid (DHA), eicosapentaenoic acid (EPA), and the specialized pro-resolving lipid mediators (SPMs) derived from polyunsaturated lipids, including DHA and EPA. Additionally, we will discuss their effects on cardiac fibrosis via NRF2 activation.
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Affiliation(s)
- Gyeoung Jin Kang
- Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; (G.J.K.); (E.J.K.)
| | - Eun Ji Kim
- Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; (G.J.K.); (E.J.K.)
- College of Pharmacy, Dongguk University, Seoul 04620, Korea
| | - Chang Hoon Lee
- College of Pharmacy, Dongguk University, Seoul 04620, Korea
- Correspondence: ; Tel.: +82-31-961-5213
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Tang K, Zheng X, Lin J, Zheng M, Lin H, Li T, Wang L. Association between non-alcoholic fatty liver disease and myocardial glucose uptake measured by 18F-fluorodeoxyglucose positron emission tomography. J Nucl Cardiol 2020; 27:1679-1688. [PMID: 30238301 DOI: 10.1007/s12350-018-1446-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 09/11/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has emerged as an independent risk factor for cardiovascular diseases. However, there were few studies evaluating the condition of myocardial glucose metabolism in patients with NAFLD. Therefore, the aim of this study was to investigate the association between NAFLD and myocardial glucose uptake assessed by using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and whether or not alteration of myocardial glucose uptake could be an indicator linking to cardiac dysfunction in NAFLD individuals. METHODS AND RESULTS A total of 743 asymptomatic subjects (201 with NAFLD, 542 without NAFLD) were retrospectively studied. The ratio of maximum myocardium FDG uptake to the mean standardized uptake value of liver (SUVratio) was calculated to estimate myocardial glucose uptake by using 18F-FDG PET. The diagnosis of fatty liver and fatty liver grading was confirmed by unenhanced CT according to diagnostic criterion of previous studies. The myocardial geometric and functional data were obtained by echocardiogram. Myocardial glucose uptake was significantly lower in individuals with NAFLD compared with those without fatty liver (P < .001). When analysis of association trend was performed, SUVratio quartiles showed correlated inversely and strongly with liver steatosis (P < .001). NAFLD patients with lower myocardial glucose uptake were more likely to have higher proportion of increased LV filling pressure (P < .05). A significant relationship between myocardial SUVratio and E/e' ratio was presented in the trend analysis (P < .05). Moreover, multivariate regression analysis showed that myocardial glucose uptake was independently associated with NAFLD after adjusting for clinical important factors (all P < .001). CONCLUSIONS The presence of NAFLD in otherwise healthy subjects is closely associated with decreased myocardial glucose uptake assessing by 18F-FDG PET imaging. Furthermore, the NAFLD individuals with lower myocardial glucose uptake are more likely to have high risk of having impaired diastolic heart function.
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Affiliation(s)
- Kun Tang
- Department of PET/CT, The First Affiliated Hospital of Wenzhou Medical University, Xuefu North Road, Wenzhou, 325000, Zhejiang, China
| | - Xiangwu Zheng
- Department of PET/CT, The First Affiliated Hospital of Wenzhou Medical University, Xuefu North Road, Wenzhou, 325000, Zhejiang, China
| | - Jie Lin
- Department of PET/CT, The First Affiliated Hospital of Wenzhou Medical University, Xuefu North Road, Wenzhou, 325000, Zhejiang, China
| | - Minghua Zheng
- Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Haixia Lin
- Department of Ultrasound, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China
| | - Tiancheng Li
- Department of PET/CT, The First Affiliated Hospital of Wenzhou Medical University, Xuefu North Road, Wenzhou, 325000, Zhejiang, China
| | - Ling Wang
- Department of Nuclear Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
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Kaya E, Yılmaz Y. Non-alcoholic fatty liver disease: A growing public health problem in Turkey. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 30:865-871. [PMID: 31258135 DOI: 10.5152/tjg.2019.18045] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is histologically classified as either non-alcoholic fatty liver or non-alcoholic steatohepatitis (NASH). NASH is the progressive subtype of NAFLD. Individuals with NASH are at significant risk of developing hepatic fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related and all-cause mortality. NAFLD is closely associated with obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome, and cardiovascular events. Its prevalence is estimated to be above 30% in Turkey; and recent studies confirm this estimate. According to these studies, the prevalence of NAFLD in Turkey is between 48.3% and 60.1%. Currently, Turkey can be considered a risky region in terms of NAFLD burden as it is the most obese country in Europe with an obesity prevalence of 32.1% according to the 2016 World Health Organization data. Moreover, along with the increasing prevalence of obesity and T2DM in Turkey, the burden of NAFLD is estimated to increase in the upcoming decade. Despite the growing burden, we lack well-designed systemic studies that investigate NAFLD and its marked histological severity. In this review, we present studies on the burden of NAFLD and NASH, the natural history of NAFLD, and its association with other systemic diseases conducted with Turkish populations.
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Affiliation(s)
- Eda Kaya
- İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Yusuf Yılmaz
- Department of Gastroenterology, Marmara University School of Medicine, İstanbul, Turkey; Marmara University Institute of Gastroenterology, İstanbul, Turkey
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12
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Yilmaz Y, Eren F. NFS Is Not a Marker of Nonalcoholic Fatty Liver Disease Per Se: What Is the True Relationship With CAD Complexity? Angiology 2020; 71:83-84. [DOI: 10.1177/0003319719862458] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey
- Institute of Gastroenterology, Marmara University, Istanbul, Turkey
| | - Fatih Eren
- Institute of Gastroenterology, Marmara University, Istanbul, Turkey
- Department of Medical Biology, School of Medicine, Marmara University, Istanbul, Turkey
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13
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Epicardial Adipose Tissue: Clinical Biomarker of Cardio-Metabolic Risk. Int J Mol Sci 2019; 20:ijms20235989. [PMID: 31795098 PMCID: PMC6929015 DOI: 10.3390/ijms20235989] [Citation(s) in RCA: 119] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 11/23/2019] [Accepted: 11/26/2019] [Indexed: 02/07/2023] Open
Abstract
Epicardial adipose tissue (EAT) is part of the visceral adipose tissue (VAT) that surrounds the heart and it is a quantifiable, modifiable, and multifaceted tissue that has both local and systemic effects. When EAT is enlarged, EAT contributes to atherosclerotic cardiovascular disease (ASCVD) risk and plays a role in the development of metabolic syndrome (MetS). In this review, we will discuss the role of EAT in various facets of MetS, including type 2 diabetes mellitus (T2DM) and insulin resistance. We examine the association between EAT and liver steatosis. We also address the correlations of EAT with HIV therapy and with psoriasis. We discuss racial differences in baseline EAT thickness. We conclude that EAT measurement serves as a powerful potential diagnostic tool in assessing cardiovascular and metabolic risk. Measurement of EAT is made less costly, more convenient, and yet accurate and reliable by transthoracic echocardiography. Furthermore, modification of EAT thickness has therapeutic implications for ASCVD, T2DM, and MetS.
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14
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Turan Y, Demir V, Turan E, Hidayet Ş. Reply to the Letter to the Editor Entitled “NFS Is Not a Marker of Nonalcoholic Fatty Liver Disease Per Se: What Is the True Relationship With CAD Complexity?”. Angiology 2019; 71:85-86. [DOI: 10.1177/0003319719870023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Yaşar Turan
- Division of Cardiology, School of Medicine, Bozok University, Yozgat, Turkey
| | - Vahit Demir
- Division of Cardiology, School of Medicine, Bozok University, Yozgat, Turkey
| | - Elif Turan
- Division of Endocrinology, School of Medicine, Bozok University, Yozgat, Turkey
| | - Şiho Hidayet
- Division of Cardiology, School of Medicine, Bozok University, Yozgat, Turkey
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15
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Association of epicardial adipose tissue with non-alcoholic fatty liver disease: a meta-analysis. Hepatol Int 2019; 13:757-765. [PMID: 31432447 DOI: 10.1007/s12072-019-09972-1] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 07/26/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Increased epicardial adipose tissue (EAT) has been proposed as a risk factor for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the association of EAT with NAFLD. METHODS The PubMed, EMBASE, and Cochrane databases were systematically reviewed by two independent investigators to identify relevant studies assessing the association of EAT thickness (EAT-t) and volume (EAT-v) with NAFLD. Comparisons between NAFLD subjects and controls were performed with meta-analysis and trial sequential analysis (TSA). RESULTS A total of thirteen case-control studies (n = 2260 patients) were included in the final analysis. The EAT was significantly increased in NAFLD patients compared with the controls (EAT, SMD: 0.73, 95% CI 0.51-0.94, p < 0.001; TSA-adjusted 95% CI 0.07-0.18; p < 0.001). When comparing the subgroups of NAFLD, the EAT-t in the severe-hepatic steatosis subgroup was thicker than that in the moderate subgroup (SMD: 1.43, 95% CI 0.15-2.71, p = 0.029). This study indicated that the EAT-t in the F3-4 fibrosis subgroup was thicker than that in the F0-2 fibrosis subgroup (SMD: 0.72, 95% CI 0.30-1.14, p = 0.001). The proportion of hypertension (OR = 1.64, 95% CI = 1.24-2.18, p = 0.001) and atherosclerotic cardiovascular disease (ASCVD) (OR = 1.66, 95% CI = 1.21-2.28, p = 0.002) was higher in the high-EAT-t group compared with the low-EAT-t group in NAFLD patients. CONCLUSIONS The EAT was increased in the NAFLD subjects compared to the controls. The increase in the EAT was associated with the severity of steatosis, fibrosis and cardiovascular disease in patients with NAFLD. These findings provide new information regarding the development and progression of NAFLD.
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16
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Er LK, Hsu LA, Juang JMJ, Chiang FT, Teng MS, Tzeng IS, Wu S, Lin JF, Ko YL. Circulating Chemerin Levels, but not the RARRES2 Polymorphisms, Predict the Long-Term Outcome of Angiographically Confirmed Coronary Artery Disease. Int J Mol Sci 2019; 20:1174. [PMID: 30866520 PMCID: PMC6429458 DOI: 10.3390/ijms20051174] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 02/24/2019] [Accepted: 03/01/2019] [Indexed: 12/12/2022] Open
Abstract
Chemerin, a novel adipokine, has been associated with metabolic, inflammatory, and atherosclerotic diseases. We aimed to determine the genetic basis of chemerin levels by conducting a genome-wide association study (GWAS) and to investigate the role of RARRES2 polymorphisms and circulating chemerin levels in the long-term outcome of coronary artery disease (CAD). A total of 2197 participants from the Taiwan Biobank (TWB) were recruited for the GWAS analysis, and 481 patients with angiographically confirmed CAD were enrolled for long-term outcome analysis. One locus of genome-wide significance with a single independent association signal was identified in the GWAS for chemerin levels with the peak association at the RARRES2 gene promoter region polymorphism rs3735167 (p = 2.35 × 10-21). In the CAD population, borderline significance was noted between RARRES2 polymorphisms and chemerin levels, whereas high chemerin levels were associated with obesity, female sex, diabetes mellitus, hypertension, current smoking, high platelet and leukocyte counts, anemia, impaired renal function, high C-reactive protein (CRP) levels, and multi-vessel disease. Kaplan⁻Meier survival curves indicated that the patients with high chemerin and CRP levels, but not those with RARRES2 polymorphisms, had a lower survival rate and higher combined cerebral and cardiovascular event rates. Combined chemerin and CRP levels further revealed a stepwise increase in poor clinical outcomes from low- to high-risk subgroups. In conclusion, rs3735167 is the lead RARRES2 polymorphism for chemerin levels in Taiwanese. Chemerin levels, but not the rs3735167 genotypes, predicted the long-term outcome of CAD, especially when combined with CRP levels.
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Grants
- TCRD-TPE-MOST-105-03, TCRD-TPE-MOST-106-01, TCRD-TPE-106-C1-1, TCRD-TPE-106-RT-3 Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
- TCMF-A 106-01-16 Buddhist Tzu Chi Medical Foundation Academic Advancement
- MOST 104-2314-B-303-013-MY3 National Science Council
- NTUH-104-S2649, NTUH-104-S2671, NTUH104-2640, NTUH104-UN001, NTUH104L005, MOST-104-2314-B-002-193-MY3, MOST 103-2314-B-002-189 Natinal taiwan univeristy hospital
- MOST 103-2314-B-002-189 and MOST 107-2314-B-002 -009 and MOST 107-2314-B-002 -261-MY3 National Science Council
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Affiliation(s)
- Leay Kiaw Er
- The Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan.
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
| | - Lung-An Hsu
- The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 33305, Taiwan.
| | - Jyh-Ming Jimmy Juang
- Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital city, Taipei 10002, Taiwan.
- Taipei, Taiwan and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
| | - Fu-Tien Chiang
- Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital city, Taipei 10002, Taiwan.
- Taipei, Taiwan and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
- Cardiovascular Center and Division of Cardiology, Fu-Jen Catholic University Hospital, New Taipei city 24352, Taiwan.
| | - Ming-Sheng Teng
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city 23142, Taiwan.
| | - I-Shiang Tzeng
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city 23142, Taiwan.
| | - Semon Wu
- Department of Life Science, Chinese Culture University, Taipei 11114, Taiwan.
| | - Jeng-Feng Lin
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
- Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city 23142, Taiwan.
| | - Yu-Lin Ko
- School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city 23142, Taiwan.
- Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city 23142, Taiwan.
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17
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Zarzour RHA, Alshawsh MA, Asif M, Al-Mansoub MA, Mohamed Z, Ahmad M, Majid AMSA, Asmawi MZ, Kaur G, Al-Dualimi DW, Yam MF. Adipocytokine Regulation and Antiangiogenic Activity Underlie the Molecular Mechanisms of Therapeutic Effects of Phyllanthus niruri against Non-Alcoholic Fatty Liver Disease. Nutrients 2018; 10:E1057. [PMID: 30096951 PMCID: PMC6115813 DOI: 10.3390/nu10081057] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 08/06/2018] [Accepted: 08/07/2018] [Indexed: 12/23/2022] Open
Abstract
The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague⁻Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.
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Affiliation(s)
- Raghdaa Hamdan Al Zarzour
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
| | - Mohammed A Alshawsh
- Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
| | - Muhammad Asif
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
- Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan.
| | - Majed Ahmed Al-Mansoub
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
| | - Zahurin Mohamed
- Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
| | - Mariam Ahmad
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
| | - Amin Malik Shah Abdul Majid
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
| | - Mohd Zaini Asmawi
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
| | - Gurjeet Kaur
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
| | - Dhamraa Waleed Al-Dualimi
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
| | - Mun Fei Yam
- Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
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Ebrahimi S, Gargari BP, Izadi A, Imani B, Asjodi F. The effects of Ramadan fasting on serum concentrations of vaspin and omentin-1 in patients with nonalcoholic fatty liver disease. Eur J Integr Med 2018. [DOI: 10.1016/j.eujim.2018.03.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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19
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Nakanishi K, Fukuda S, Tanaka A, Otsuka K, Taguchi H, Shimada K. Relationships Between Periventricular Epicardial Adipose Tissue Accumulation, Coronary Microcirculation, and Left Ventricular Diastolic Dysfunction. Can J Cardiol 2017; 33:1489-1497. [DOI: 10.1016/j.cjca.2017.08.001] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 08/02/2017] [Accepted: 08/02/2017] [Indexed: 01/23/2023] Open
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20
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Rabkin SW. Is Reduction in Coronary Blood Flow the Mechanism by Which Epicardial Fat Produces Left Ventricular Diastolic Dysfunction? Can J Cardiol 2017; 33:1459-1461. [DOI: 10.1016/j.cjca.2017.08.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Revised: 08/15/2017] [Accepted: 08/15/2017] [Indexed: 01/24/2023] Open
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Rietdorf K, MacQueen H. Investigating interactions between epicardial adipose tissue and cardiac myocytes: what can we learn from different approaches? Br J Pharmacol 2017; 174:3542-3560. [PMID: 27882550 PMCID: PMC5610165 DOI: 10.1111/bph.13678] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 11/14/2016] [Accepted: 11/18/2016] [Indexed: 01/08/2023] Open
Abstract
Heart disease is a major cause of morbidity and mortality throughout the world. Some cardiovascular conditions can be modulated by lifestyle factors such as increased exercise or a healthier diet, but many require surgical or pharmacological interventions for their management. More targeted and less invasive therapies would be beneficial. Recently, it has become apparent that epicardial adipose tissue plays an important role in normal and pathological cardiac function, and it is now the focus of considerable research. Epicardial adipose tissue can be studied by imaging of various kinds, and these approaches have yielded much useful information. However, at a molecular level, it is more difficult to study as it is relatively scarce in animal models and, for practical and ethical reasons, not always available in sufficient quantities from patients. What is needed is a robust model system in which the interactions between epicardial adipocytes and cardiac myocytes can be studied, and physiologically relevant manipulations performed. There are drawbacks to conventional culture methods, not least the difficulty of culturing both cardiac myocytes and adipocytes, each of which has special requirements. We discuss the benefits of a three-dimensional co-culture model in which in vivo interactions can be replicated. LINKED ARTICLES This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.
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Affiliation(s)
- Katja Rietdorf
- School of Life, Health and Chemical SciencesThe Open UniversityMilton KeynesUK
| | - Hilary MacQueen
- School of Life, Health and Chemical SciencesThe Open UniversityMilton KeynesUK
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22
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Cho KI, Jo EA, Cho SH, Kim BH. The Influence of Epicardial Fat and Nonalcoholic Fatty Liver Disease on Heart Rate Recovery in Metabolic Syndrome. Metab Syndr Relat Disord 2017; 15:226-232. [DOI: 10.1089/met.2016.0132] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Kyoung Im Cho
- Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea
- Convergence Medicine and Exercise Science Research Institute, Kosin University College of Medicine, Busan, South Korea
| | - Eun Ah Jo
- Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea
- Convergence Medicine and Exercise Science Research Institute, Kosin University College of Medicine, Busan, South Korea
| | - Sang Hoon Cho
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea
| | - Bo Hyun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Hospital and Biomedical Research Institute, Busan, South Korea
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23
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Polyzos SA, Kountouras J, Mantzoros CS. Adipokines in nonalcoholic fatty liver disease. Metabolism 2016; 65:1062-79. [PMID: 26725002 DOI: 10.1016/j.metabol.2015.11.006] [Citation(s) in RCA: 253] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Revised: 11/19/2015] [Accepted: 11/20/2015] [Indexed: 12/13/2022]
Abstract
Since the discovery of adipose tissue as a higly active endocrine tissue, adipokines, peptides produced by adipose tissue and exerting autocrine, paracrine and endocrine function, have gained increasing interest in various obesity-related diseases, including nonalcoholic fatty liver disease (NAFLD). Data regarding the association between NAFLD and circulating leptin and adiponectin levels are generally well documented: leptin levels increase, whereas adiponectin levels decrease, by increasing the severity of NAFLD. Data regarding other adipokines in histologically confirmed NAFLD populations are inconclusive (e.g., resistin, visfatin, retinol-binding protein-4, chemerin) or limited (e.g., adipsin, obestatin, omentin, vaspin etc.). This review summarizes evidence on the association between adipokines and NAFLD. The first part of the review provides general consideration on the interplay between adipokines and NAFLD, and the second part provides evidence on specific adipokines possibly involved in NAFLD pathogenesis. A thorough insight into the pathophysiologic mechanisms linking adipokines with NAFLD may result in the design of studies investigating the combined adipokine use as noninvasive diagnostic markers of NAFLD and new clinical trials targeting the treatment of NAFLD.
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Affiliation(s)
- Stergios A Polyzos
- Second Medical Clinic, Department of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece.
| | - Jannis Kountouras
- Second Medical Clinic, Department of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA
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24
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Sunbul M, Kivrak T, Durmus E, Akin H, Aydin Y, Ergelen R, Yilmaz Y, Agirbasli M. Nonalcoholic Steatohepatitis Score is an Independent Predictor of Right Ventricular Dysfunction in Patients with Nonalcoholic Fatty Liver Disease. Cardiovasc Ther 2016. [PMID: 26202098 DOI: 10.1111/1755-5922.12145] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease and impaired left ventricular (LV) function, yet the impact of NAFLD on right ventricular (RV) function remains unclear. We investigate the RV functional properties in patients with NAFLD. METHODS Ninety consecutive patients with the diagnosis of biopsy-proven NAFLD and 45 age- and sex-matched controls were included. All patients underwent an echocardiographic examination. RV function was evaluated by two-dimensional (2D) speckle-tracking echocardiography (STE). RESULTS Mean fibrosis stage and nonalcoholic steatohepatitis (NASH) scores were 1.3 ± 1.1 and 5.2 ± 1.6, respectively. NAFLD patients displayed decreased RV function compared to controls. NAFLD patients with liver fibrosis (67 patients) had significantly lower RV function assessed by GLS (global longitudinal strain) compared to patients without liver fibrosis (18.9 ± 3.4% vs. 21.6 ± 2.3%, P < 0.001). NASH score ≥5 was associated with lower RV-GLS (18.9 ± 3.1% vs. 21.0 ± 3.4%, P = 0.006). NASH score inversely correlated with RV-GLS (r = -0.370, P < 0.001) such as patients with impaired RV-GLS (<19%) showed significantly higher NASH score compared to normal RV-GLS group (5.8 ± 1.4 vs. 4.8 ± 1.7, P = 0.009). Logistic regression analysis revealed that NASH score was an independent predictor of impaired RV function in patients with NAFLD. CONCLUSIONS Patients with NAFLD have impaired RV function. NASH score inversely correlates with RV-GLS and independently predicts impaired RV function in patients with NAFLD.
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Affiliation(s)
- Murat Sunbul
- Department of Cardiology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Tarik Kivrak
- Cardiology Clinic, Sivas Numune Hospital, Sivas, Turkey
| | - Erdal Durmus
- Cardiology Clinic, Silifke State Hospital, Mersin, Turkey
| | - Hakan Akin
- Department of Gastroenterology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Yucel Aydin
- Department of Gastroenterology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Rabia Ergelen
- Department of Radiology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Yusuf Yilmaz
- Department of Gastroenterology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Mehmet Agirbasli
- Department of Cardiology, Marmara University Faculty of Medicine, Istanbul, Turkey
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Ozturk O, Colak Y, Senates E, Yilmaz Y, Ulasoglu C, Doganay L, Ozkanli S, Oltulu YM, Coskunpinar E, Tuncer I. Increased serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels in patients with biopsy-proven nonalcoholic fatty liver disease. World J Gastroenterol 2015; 21:8096-8102. [PMID: 26185381 PMCID: PMC4499352 DOI: 10.3748/wjg.v21.i26.8096] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2015] [Revised: 04/02/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) patients. METHODS Fifty-three consecutive, biopsy-proven NAFLD patients (31 males and 22 females, mean age 42.5 ± 9.6 years) and 26 age- and gender-matched, healthy controls (14 males and 12 females, mean age 39 ± 10.7 years) were included. The patients with NAFLD were consecutive patients who had been admitted to the hepatology outpatient clinic within the last year and had been diagnosed with NAFLD as the result of liver biopsy. The healthy controls were individuals who attended the outpatient clinic for routine health control and had no known chronic illnesses. The histological evaluation was conducted according to the NAFLD activity scoring system recommended by The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. The serum LOX-1 levels were measured using an ELISA kit (Life Science Inc. USCN. Wuhan, Catalog No. E1859Hu) in both patients and healthy controls. A receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value of LOX-1 and thereby distinguish between patients with nonalcoholic steatohepatitis (NASH) and healthy controls. A P-value < 0.05 was considered statistically significant. RESULTS NAFLD and healthy control groups were similar in terms of age and sex. NAFLD patients consisted of 8 patients with simple steatosis (15%), 27 with borderline NASH (51%) and 18 with definitive NASH (34%). Metabolic syndrome was found in 62.2% of the patients with NAFLD. The mean serum LOX-1 level in biopsy-proven NAFLD patients was 8.49 ± 6.43 ng/mL compared to 4.08 ± 4.32 ng/mL in healthy controls (P = 0.001). The LOX-1 levels were significantly different between controls, simple steatosis and NASH (borderline+definite) cases (4.08 ± 4.32 ng/mL, 6.1 ± 6.16 ng/mL, 8.92 ± 6.45 ng/mL, respectively, P = 0.004). When the cut-off value for the serum LOX-1 level was set at 5.35 ng/mL, and a ROC curve analysis was performed to distinguish between steatohepatitis patients and controls; the sensitivity and specificity of the serum LOX-1 level were 69.8% and 69.2%, respectively. CONCLUSION The serum LOX-1 levels were significantly higher in NAFLD patients than in healthy controls. Additionally, the serum LOX-1 levels could differentiate between steatohepatitis patients and healthy controls.
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Epicardial fat volume quantification by noncontrast CT: Trimming away the fat from the meat. J Cardiovasc Comput Tomogr 2015; 9:310-2. [DOI: 10.1016/j.jcct.2015.05.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Revised: 04/23/2015] [Accepted: 05/02/2015] [Indexed: 11/22/2022]
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Mediatory effect of circulating vaspin on resting metabolic rate in obese individuals. Eur J Nutr 2015; 55:1297-305. [PMID: 26058881 DOI: 10.1007/s00394-015-0948-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Accepted: 05/31/2015] [Indexed: 10/23/2022]
Abstract
BACKGROUND/OBJECTIVE Vaspin is a recently identified adipokine related to obesity and insulin sensitivity. The precise mechanism of vaspin in the body is not well known, and its function in resting metabolic rate (RMR) is even less understood. Therefore, the main aim of this study was to investigate the effect of circulating vaspin on RMR in obese people. MATERIALS AND METHODS A total of 222 obese participants were included in the current comparative cross-sectional study. Body composition was measured using body composition analyzer. RMR was measured by means of indirect calorimetry. For the measurement of vaspin serum concentrations, an enzyme-linked immunosorbent assay was used. Dietary intake was assessed using 3-day 24-h dietary recall. RESULTS Between low and high circulating vaspin groups, there was significant difference for sex (P = 0.03), fat percent (P = 0.008), RMR per weight (P < 0.001), and RMR per fat free mass (FFM) (P = 0.007). However, there was no statistical difference between the groups in dietary intake after adjustment for energy intake (P > 0.05). Furthermore, individuals with higher level of RMR had higher vaspin concentration. Weight, visceral fat, FFM, and fat mass had significant effect on increasing RMR (P < 0.05) but after adding vaspin as a covariate in the general linear model; visceral fat (P = 0.078) and fat mass (P = 0.339) missed their effectiveness. CONCLUSION Circulating vaspin level is higher in women than in men in obese individuals. Moreover, it was found that vaspin had mediator effect between visceral fat and fat mass associations with RMR in obese participants.
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Abstract
Epicardial adipose tissue is a unique and multifaceted fat depot with local and systemic effects. This tissue is distinguished from other visceral fat depots by a number of anatomical and metabolic features, such as increased fatty acid metabolism and a unique transcriptome enriched in genes that are associated with inflammation and endothelial function. Epicardial fat and the heart share an unobstructed microcirculation, which suggests these tissues might interact. Under normal physiological conditions, epicardial fat has metabolic, thermogenic (similar to brown fat) and mechanical (cardioprotective) characteristics. Development of pathological conditions might drive the phenotype of epicardial fat such that it becomes harmful to the myocardium and the coronary arteries. The equilibrium between protective and detrimental effects of this tissue is fragile. Expression of the epicardial-fat-specific transcriptome is downregulated in the presence of severe and advanced coronary artery disease. Improved local vascularization, weight loss and targeted medications can restore the protective physiological functions of epicardial fat. Measurements of epicardial fat have several important applications in the clinical setting: accurate measurement of its thickness or volume is correlated with visceral adiposity, coronary artery disease, the metabolic syndrome, fatty liver disease and cardiac changes. On account of this simple clinical assessment, epicardial fat is a reliable marker of cardiovascular risk and an appealing surrogate for assessing the efficacy of drugs that modulate adipose tissues.
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Affiliation(s)
- Gianluca Iacobellis
- Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Miller School of Medicine, University of Miami, 1400 NW 10th Avenue, Dominion Tower suite 805-807, Miami, FL 33136, USA
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Dal Lin C, Tona F, Osto E. Coronary Microvascular Function and Beyond: The Crosstalk between Hormones, Cytokines, and Neurotransmitters. Int J Endocrinol 2015; 2015:312848. [PMID: 26124827 PMCID: PMC4466475 DOI: 10.1155/2015/312848] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 03/10/2015] [Accepted: 03/16/2015] [Indexed: 01/18/2023] Open
Abstract
Beyond its hemodynamic function, the heart also acts as a neuroendocrine and immunoregulatory organ. A dynamic communication between the heart and other organs takes place constantly to maintain cardiovascular homeostasis. The current understanding highlights the importance of the endocrine, immune, and nervous factors to fine-tune the crosstalk of the cardiovascular system with the entire body. Once disrupted, this complex interorgan communication may promote the onset and the progression of cardiovascular diseases. Thus, expanding our knowledge on how these factors influence the cardiovascular system can lead to novel therapeutic strategies to improve patient care. In the present paper, we review novel concepts on the role of endocrine, immune, and nervous factors in the modulation of microvascular coronary function.
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Affiliation(s)
- Carlo Dal Lin
- Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Via Giustiniani 2, 35100 Padua, Italy
| | - Francesco Tona
- Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Via Giustiniani 2, 35100 Padua, Italy
| | - Elena Osto
- Centre for Molecular Cardiology, University of Zurich and University Heart Center, Department of Cardiology, University Hospital, Raemistrasse 100, 8091 Zurich, Switzerland
- *Elena Osto:
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Kłusek-Oksiuta M, Bialokoz-Kalinowska I, Tarasów E, Wojtkowska M, Werpachowska I, Lebensztejn DM. Chemerin as a novel non-invasive serum marker of intrahepatic lipid content in obese children. Ital J Pediatr 2014; 40:84. [PMID: 25399407 PMCID: PMC4237733 DOI: 10.1186/s13052-014-0084-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Accepted: 10/12/2014] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Ectopic hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of non-alcoholic fatty liver disease (NAFLD). The current study has shown that fat tissue constitutes an important endocrine organ with its own production and metabolism of many biologically active substances, among which adipokines play an important role. Classic adipokines (e.g. leptin, adiponectin, resistin) are fat-derived hormones which serum level is altered in patients with NAFLD. The role of novel adipokines in the pathomechanism of this disease is not clear. Therefore, the aim of our study was to evaluate the serum concentrations of chemerin, omentin and vaspin in obese children with NAFLD. METHODS Forty-five obese children, aged 7-17 years old, were admitted to our Department with suspected liver disease (hepatomegaly, and/or ultrasonographic liver brightness, and/or increased ALT activity). Viral hepatitides, as well as autoimmune and metabolic liver diseases were excluded. Fasting serum levels of chemerin, omentin and vaspin were determined. The grade of liver steatosis in ultrasound was graded according to Saverymuttu. (1)HMR spectroscopy was performed with a 1.5 T scanner and with PRESS sequencing. RESULTS Fatty liver was confirmed in 39 children by ultrasound and in 33 patients by (1)HMRS (19 of them also had increased ALT activity /NAFLD/). Chemerin and vaspin levels were significantly higher in children with NAFLD compared to the control group (n = 30). The concentration of chemerin was significantly higher in children with advanced liver steatosis compared to non-hepatopathic patients (p = 0,02). Significant positive correlations were found between the total liver lipids in (1)HMRS and chemerin (r = 0,33; p = 0,02) and vaspin (r = 0,4; p = 0,006). The ability of serum chemerin (cut-off = 190 ng/ml, Se = 75%, Sp = 58%) to differentiate children with fatty liver in (1)HMRS from those without steatosis was significant (AUC = 0,7, p = 0,04). Omentin and vaspin did not allow a useful prediction to be made. CONCLUSION Chemerin seems to be the most suitable non-invasive biomarker in predicting both intrahepatic lipid content in obese children and advanced liver steatosis in children with NAFLD.
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Affiliation(s)
- Monika Kłusek-Oksiuta
- Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, 17 Waszyngtona St., Bialystok, 15-274, Poland.
| | - Irena Bialokoz-Kalinowska
- Department of Pediatrics and Developmental Disorders, Medical University of Bialystok, Bialystok, Poland.
| | - Eugeniusz Tarasów
- Department of Radiology, Medical University of Bialystok, Bialystok, Poland.
| | - Malgorzata Wojtkowska
- Department of Radiology, University Teaching Children's Hospital, Bialystok, Poland.
| | - Irena Werpachowska
- Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, 17 Waszyngtona St., Bialystok, 15-274, Poland.
| | - Dariusz Marek Lebensztejn
- Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, 17 Waszyngtona St., Bialystok, 15-274, Poland.
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Farhangi MA, Alipour B, Jafarvand E, Khoshbaten M. Oral coenzyme Q10 supplementation in patients with nonalcoholic fatty liver disease: effects on serum vaspin, chemerin, pentraxin 3, insulin resistance and oxidative stress. Arch Med Res 2014; 45:589-95. [PMID: 25450583 DOI: 10.1016/j.arcmed.2014.11.001] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Accepted: 11/03/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUNDS AND AIMS Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Chronic exposure to oxidative stress leads to depletion of liver antioxidants and abnormal cytokine production; antioxidant therapy is one of the main therapeutic lines in NAFLD. In the current study we aimed to investigate the effect of coenzyme Q10 (coQ10) therapy on several adipocytokines and insulin resistance in patients with NAFLD. METHODS In the current randomized double-blind placebo controlled trial 44 NAFLD patients were enrolled. After randomization into two groups, 22 patients received 100 mg/day coQ10 capsules and 22 patients received placebo daily for 4 weeks. BMI and WHR were calculated for patients at the beginning and end of the study and blood samples were obtained from the patients to measure serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting serum glucose (FSG), insulin resistance (IR), vaspin, chemerin, pentraxin 3 (PTX3) and markers of oxidative stress including total antioxidant capacity (TAC) and malondialdehyde (MDA). RESULTS After 4 weeks of coQ10 supplementation, waist circumference (WC) and serum AST and TAC concentrations significantly decreased in intervention group (p <0.05) but no significant changes occurred in placebo-treated group. In stepwise multivariate linear regression model, change in serum FSG was a significant predictor of changes in serum vaspin, chemerin and pentraxin 3 (p <0.001). CONCLUSIONS The present study showed a potential for coQ10 therapy in improving several anthropometric and biochemical variables in NAFLD. Longer studies with higher doses of coQ10 are required to further evaluate this potential benefit.
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Affiliation(s)
| | - Beytollah Alipour
- Department of Community Nutrition, School of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Elnaz Jafarvand
- Department of Community Nutrition, School of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Manouchehr Khoshbaten
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Sunbul M, Agirbasli M, Durmus E, Kivrak T, Akin H, Aydin Y, Ergelen R, Yilmaz Y. Arterial stiffness in patients with non-alcoholic fatty liver disease is related to fibrosis stage and epicardial adipose tissue thickness. Atherosclerosis 2014; 237:490-3. [PMID: 25463079 DOI: 10.1016/j.atherosclerosis.2014.10.004] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2014] [Revised: 09/18/2014] [Accepted: 10/04/2014] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) is associated with atherosclerosis and reduced vascular compliance. The purpose of this study was to examine the relationships between arterial stiffness measures, the histological severity of NAFLD, and epicardial fat thickness (EFT). METHODS A total of 100 patients with biopsy-proven NAFLD and 50 age- and sex-matched controls were enrolled. The histological severity was assessed in all NAFLD patients. Measurements of arterial stiffness [pulse-wave velocity (PWV) and augmentation index (AIx)] were carried out using a Mobil-O-Graph arteriograph system. EFT was assessed by means of echocardiography. RESULTS Compared with controls, NAFLD patients had significantly higher PWV and AIx values. Stepwise linear regression analysis demonstrated that the liver fibrosis score and EFT were independent predictors of both PWV and AIx values in NAFLD patients. CONCLUSIONS Patients with NAFLD have an increased arterial stiffness, which reflects both the severity of liver fibrosis and increased EFT values.
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Affiliation(s)
- Murat Sunbul
- Department of Cardiology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Mehmet Agirbasli
- Department of Cardiology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Erdal Durmus
- Cardiology Clinic, Silifke State Hospital, Mersin, Turkey
| | - Tarik Kivrak
- Cardiology Clinic, Sivas Numune Hospital, Sivas, Turkey
| | - Hakan Akin
- Department of Gastroenterology, School of Medicine, Marmara University, Fevzi Cakmak Mah, Mimar Sinan Cad. No. 41 Ust Kaynarca, Pendik, Istanbul, Turkey
| | - Yucel Aydin
- Department of Gastroenterology, School of Medicine, Marmara University, Fevzi Cakmak Mah, Mimar Sinan Cad. No. 41 Ust Kaynarca, Pendik, Istanbul, Turkey
| | - Rabia Ergelen
- Department of Radiology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Marmara University, Fevzi Cakmak Mah, Mimar Sinan Cad. No. 41 Ust Kaynarca, Pendik, Istanbul, Turkey; Institute of Gastroenterology, Marmara University, Basibuyuk, Maltepe, Istanbul 34840, Turkey.
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Abstract
PURPOSE OF REVIEW We comment on the associations between epicardial adiposity and cardiovascular disease (CVD) and associated risk factors. The effects of lifestyle measures and CVD drugs on cardiac adipose tissue are also discussed. RECENT FINDINGS Epicardial adipose tissue exerts cardioprotective properties; however, in cases of pathological enlargement, epicardial fat can lead to myocardial inflammation and dysfunction as well as left ventricular hypertrophy and coronary artery disease (CAD) due to paracrine actions that include increased production of reactive oxygen species, atherogenic and inflammatory cytokines. Cardiac adiposity is associated with CAD, obesity, type 2 diabetes, metabolic syndrome, nonalcoholic fatty liver disease, and chronic kidney disease, as well as with CVD risk factors such as lipids, hypertension, obesity markers, and carotid atherosclerosis. SUMMARY Due to its anatomical and functional proximity to the coronary circulation, epicardial adipose tissue may represent an even more direct CVD risk marker than central adiposity. Lifestyle measures and certain drugs may affect its thickness, although there are limited data currently available. The clinical implications of epicardial fat in daily practice remain to be established in future studies.
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Iacobellis G, Barbarini G, Letizia C, Barbaro G. Epicardial fat thickness and nonalcoholic fatty liver disease in obese subjects. Obesity (Silver Spring) 2014; 22:332-6. [PMID: 24115757 DOI: 10.1002/oby.20624] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Revised: 08/16/2013] [Accepted: 09/10/2013] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Ectopic fat accumulation within the heart and the liver are linked to an increased cardiovascular risk. Ultrasound-measured cardiac and liver steatosis are easily accessible markers of intra-organ ectopic fat accumulation. The hypothesis that echocardiographic epicardial fat thickness is independently associated with nonalcoholic fatty liver disease (NAFLD) in obese subjects is tested. DESIGN AND METHODS Sixty-two obese (BMI > 30 kg m⁻²) subjects with ultrasonographic evidence of NAFLD and 62 control obese subjects without history or signs of NAFLD underwent echocardiographic epicardial fat thickness measurement. RESULTS Epicardial fat thickness was significantly higher (P < 0.01) in obese subjects with NAFLD when compared to those without NAFLD. Epicardial fat thickness was significantly higher (9.7 ± 0.2 vs. 8 ± 0.7 mm, P < 0.01) in subjects with severe (ultrasound score 3) than those with moderate (score 2) liver steatosis. Among waist circumference and BMI, epicardial fat thickness resulted in the best independent correlate of liver steatosis (R² = 0.77, P < 0.001). CONCLUSIONS Our study suggests that epicardial fat is a good predictor of liver steatosis in obese subjects. Echocardiographic epicardial fat predicts ultrasound-measured fatty liver better than BMI or waist circumferences does. Patients with severe fatty liver infiltration presented with the highest amount of cardiac fat accumulation.
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Affiliation(s)
- Gianluca Iacobellis
- Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
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Çetin M, Kocaman SA, Durakoğlugil ME, Erdoğan T, Ergül E, Dogan S, Canga A. Effect of epicardial adipose tissue on diastolic functions and left atrial dimension in untreated hypertensive patients with normal systolic function. J Cardiol 2013; 61:359-64. [PMID: 23473765 DOI: 10.1016/j.jjcc.2012.12.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2012] [Revised: 11/25/2012] [Accepted: 12/21/2012] [Indexed: 01/30/2023]
Abstract
BACKGROUND Adipose tissue is the source of many adipokines affecting the cardiovascular system either locally or systemically. Although hypertension is one of the most important factors in diastolic dysfunction (DD), the exact cause of this relationship is unknown. There is no specific study in the current literature regarding the association of epicardial adipose tissue (EAT) with left ventricular DD in patients with essential hypertension. METHODS The present study was cross-sectional and observational, including 127 patients with untreated hypertension who underwent a complete transthoracic echocardiographic examination as well as measurements of EAT and diastolic parameters. RESULTS EAT was significantly correlated with left atrial dimension, DD parameters, and left ventricular (LV) mass as well as age and blood pressure measurements. EAT was also correlated with Framingham risk score (p<0.001). Age and EAT were significantly increased in patients with high grades of DD compared to those with low values (p<0.001 and p=0.001, respectively). Linear regression analyses revealed EAT as an independent predictor of all DD parameters. The area under the curve values of EAT were similar to age and higher than those of LV mass and mean BP for both the presence of DD and grade two DD. CONCLUSION Based on our findings, increased EAT may be associated with diastolic dysfunction and left atrial dilatation due to local or systemic effects in untreated hypertensive patients. This relationship is independent of and stronger than abdominal obesity, implicating the clinical importance of measuring EAT thickness.
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Affiliation(s)
- Mustafa Çetin
- Rize Education and Research Hospital, Department of Cardiology, Rize, Turkey
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Rourke JL, Dranse HJ, Sinal CJ. Towards an integrative approach to understanding the role of chemerin in human health and disease. Obes Rev 2013; 14:245-62. [PMID: 23216632 DOI: 10.1111/obr.12009] [Citation(s) in RCA: 188] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Revised: 10/22/2012] [Accepted: 11/01/2012] [Indexed: 12/19/2022]
Abstract
Chemerin is an adipocyte-secreted protein with autocrine/paracrine roles on adipose development and function as well as endocrine roles in metabolism and immunity. Following prochemerin secretion, protease-mediated generation of chemerin isoforms with a range of biological activities is a key regulatory mechanism controlling local, context-specific chemerin bioactivity. Together, experimental and clinical data indicate that localized and/or circulating chemerin expression and activation are elevated in numerous metabolic and inflammatory diseases including psoriasis, obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease. These elevations are positively correlated with deleterious changes in glucose, lipid, and cytokine homeostasis, and may serve as a link between obesity, inflammation and other metabolic disorders. This review highlights the current state of knowledge regarding chemerin expression, processing, biological function and relevance to human disease, particularly with respect to adipose tissue development, inflammation, glucose homeostasis and cardiovascular disease. Furthermore, it discusses study variability, deficiencies in current measurement, and questions concerning chemerin function in disease, with a special emphasis on techniques and tools used to properly assess chemerin biology. An integration of basic and clinical research is key to understanding how chemerin influences disease pathobiology, and whether modulation of chemerin levels and/or activity may serve as a potential method to prevent and treat metabolic diseases.
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Affiliation(s)
- J L Rourke
- Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
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Al-Azzam SI, Alzoubi KH, Abeeleh JA, Mhaidat NM, Abu-Abeeleh M. Effect of statin therapy on vaspin levels in type 2 diabetic patients. Clin Pharmacol 2013; 5:33-8. [PMID: 23449848 PMCID: PMC3581289 DOI: 10.2147/cpaa.s42496] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Statins are commonly used antihyperlipidemic agents, with anti-inflammatory and immunomodulatory properties that are thought to account for a significant portion of their ability to protect against atherosclerosis and cardiovascular disease. Vaspin, a visceral adipose tissue-derived serine protease inhibitor, is an emerging adipokine with important insulin-sensitizing, cardioprotective, and antiatherosclerotic properties in patients with diabetes. In this randomized controlled clinical trial, we evaluated the effect of statin therapy on vaspin levels in patients with type 2 diabetes mellitus. METHODS Patients were divided into two groups, ie, those receiving simvastatin (study group, n = 33), and those who did not (control group, n = 29). Patient data, blood biochemistry, and vaspin levels were recorded at the beginning of the study (baseline) and after 8 weeks (end of the study). RESULTS After 8 weeks of treatment, vaspin levels were increased in patients treated with simvastatin (504.58 ± 203.07 pg/mL at baseline versus 629.15 ± 68.39 pg/mL after 8 weeks, P < 0.01), but not in patients who were not treated with simvastatin (613.33 ± 357.53 pg/mL at baseline versus 582.37 ± 84.63 pg/mL after 8 weeks, P > 0.05). In addition, the lipid-lowering effect of simvastatin was reflected in a statistically significant reduction in total cholesterol in the study group (220.75 ± 55.66 mg/dL at baseline versus 201.90 ± 53.65 mg/dL after 8 weeks P < 0.01) but not in the control group (214.24 ± 47.2 mg/dL at baseline versus 215.72 ± 43.65 mg/dL after 8 weeks, P > 0.05) and in a statistically significant reduction in triglyceride levels in the study group (265.8 ± 210.41 mg/dL at baseline versus 223.03 ± 178.67 mg/dL after 8 weeks, P < 0.05) but not in the control group (225.44 ± 115.13 mg/dL at baseline versus 215.58 ± 110.2 mg/dL after 8 weeks, P > 0.05). Mean vaspin levels were significantly higher in the study group than in the control group. CONCLUSION These results indicate that statin therapy increases plasma vaspin levels in addition to having a lipid-lowering effect. This could be a mechanism underlying the pleiotropic effects seen with statins, including their cardioprotective and antiatherosclerotic effects.
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Affiliation(s)
- Sayer I Al-Azzam
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
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Alp H, Karaarslan S, Selver Eklioğlu B, Atabek ME, Altın H, Baysal T. Association between nonalcoholic fatty liver disease and cardiovascular risk in obese children and adolescents. Can J Cardiol 2012; 29:1118-25. [PMID: 23040432 DOI: 10.1016/j.cjca.2012.07.846] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2012] [Revised: 07/30/2012] [Accepted: 07/31/2012] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The recent rise in the prevalence of obesity likely explains nonalcoholic fatty liver disease (NAFLD) epidemic worldwide. We evaluated cardiac functions, cardiovascular risk, and associated parameters with grades of NAFLD in obese children. METHODS Four hundred obese children were enrolled in the study. Obese children with NAFLD were classified in 2 subgroups according to ultrasonographic visualizing. Ninety-three obese children with NAFLD (mean age 11.73 ± 2.72 years in group 2 and 12.69 ± 2.61 years in group 3) were compared with 307 age- and sex-matched non-NAFLD obese children and 150 control subjects. Laboratory parameters were measured during the fasting state. Pulsed and tissue Doppler echocardiography were performed. Intima-media (IMT) and epicardial adipose tissue (EAT) thicknesses were measured. RESULTS NAFLD groups had a significantly higher body mass index (29.15 ± 3.42 and 30.46 ± 4.60; P < 0.001), total adipose tissue mass (37.95 ± 4.46% and 46.57 ± 6.45%; P < 0.001), higher insulin, alanine aminotransferase, and aspartate aminotransferase levels. Increased end-systolic thickness of the interventricular septum (P < 0.001), larger left ventricular mass (P < 0.003) and index (P < 0.003) were found in NAFLD groups. Children with NAFLD had higher Tei index values. Also, carotid artery IMT and EAT thickness were significantly higher in obese children. Waist and hip circumference, total cholesterol level, total adipose tissue mass, and interventricular septum were statistically different in NAFLD groups. CONCLUSIONS Children with NAFLD had mildly altered left and right ventricular functions and all obese children had increased IMT and EAT thickness. Also, grade of liver steatosis was positively correlated with total adipose tissue mass and interventricular septum systolic thickness.
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Affiliation(s)
- Hayrullah Alp
- Department of Pediatric Cardiology, Necmettin Erbakan University, Meram School of Medicine Hospital, Konya, Turkey.
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Bian Z, Ma X. Liver fibrogenesis in non-alcoholic steatohepatitis. Front Physiol 2012; 3:248. [PMID: 22934006 PMCID: PMC3429026 DOI: 10.3389/fphys.2012.00248] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2012] [Accepted: 06/17/2012] [Indexed: 12/13/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common chronic liver diseases in developed western countries. Non-alcoholic steatohepatitis (NASH) is the most severe form of NAFLD, and can progress to more severe forms of liver disease, including fibrosis, cirrhosis, and even hepatocellular carcinoma. The activation of hepatic stellate cells plays a critical role in NASH-related fibrogenesis. Multiple factors, such as insulin resistance, oxidative stress, pro-inflammatory cytokines and adipokines, and innate immune responses, are known to contribute to the development of NASH-related fibrogenesis. Furthermore, these factors may share synergistic interactions, which could contribute to the process of liver fibrosis. Given the complex etiology of NASH, combined treatment regimes that target these different factors provide potential treatment strategies for NASH-related liver fibrosis.
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Affiliation(s)
- Zhaolian Bian
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao-Tong University School of Medicine Shanghai, China
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Colak Y, Karabay CY, Tuncer I, Kocabay G, Kalayci A, Senates E, Ozturk O, Doganay HL, Enc FY, Ulasoglu C, Kiziltas S. Relation of epicardial adipose tissue and carotid intima-media thickness in patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2012; 24:613-618. [PMID: 22495402 DOI: 10.1097/meg.0b013e3283513f19] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVE Currently, nonalcoholic fatty liver disease (NAFLD) itself has been accepted as an atherosclerotic risk factor and related to increased cardiovascular disease risk. In this study, we aimed to investigate the relationship of epicardial fat thickness (EFT), a parameter associated with atherosclerosis in recent years, with carotid artery intima-media thickness (C-IMT), another parameter of subclinical atherosclerosis. DESIGN AND METHODS We investigated 57 patients with biopsy-proven NAFLD and 30 age-matched and sex-matched controls. EFT was obtained by transthoracic echocardiography and C-IMT was evaluated by an ultrasonographic measurement using a linear type B-mode probe. RESULTS EFT and C-IMT were significantly higher in NAFLD patients compared with the controls (EFT: 0.58 ± 0.18 vs. 0.36 ± 0.17 cm, P<0.001 and C-IMT: 0.64 ± 0.1 vs. 0.52 ± 0.1 mm, P<0.001, respectively). We found a statistically significant correlation between EFT and BMI, C-IMT, waist circumference, homeostasis model assessment of insulin resistance, and nonalcoholic steatohepatitis scores in both groups. Stepwise regression analysis showed that C-IMT (β=0.36, t=2.86, P=0.006) and waist circumference (β=0.3, t=2.44, P=0.018), in the order they entered into the model, were independent predictors of EFT in patients with NAFLD. CONCLUSION Our findings indicate that EFT and C-IMT were significantly higher in patients with NAFLD compared with the controls and waist circumference and C-IMT are independent predictors for EFT in patients with NAFLD.
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Affiliation(s)
- Yasar Colak
- Department of Gastroenterology, Istanbul Goztepe Education and Research Hospital, Istanbul, Turkey.
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Yilmaz Y. Review article: fructose in non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2012; 35:1135-44. [PMID: 22469071 DOI: 10.1111/j.1365-2036.2012.05080.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 02/22/2012] [Accepted: 03/09/2012] [Indexed: 12/15/2022]
Abstract
BACKGROUND The role of excess fructose intake in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has recently received increasing attention, but the pathophysiology of this relationship has been only partly elucidated. AIM To provide an overview of the potential role played by fructose in the pathogenesis of NAFLD by focusing on both indirect and direct harmful effects. METHODS Experimental and clinical studies which investigated the relation of fructose with NAFLD are reviewed. RESULTS Several factors may potentially contribute to fructose-induced NAFLD, including the induction of the metabolic syndrome, copper deficiency, bacterial translocation from the gut to the liver, the formation of advanced glycation endproducts and a direct dysmetabolic effect on liver enzymes. CONCLUSIONS Experimentally-increased fructose intake recapitulates many of the pathophysiological characteristics of the metabolic syndrome in humans, which may in turn lead to NAFLD. However, the majority of experimental studies tend to involve feeding excessively high levels of fructose (60-70% of total energy intake) which is not reflective of average human intake. Hopefully, the combination of in vivo, in vitro and genetic research will provide substantial mechanistic evidence into the role of fructose in NAFLD development and its complications.
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Affiliation(s)
- Y Yilmaz
- Institute of Gastroenterology, Marmara University, Istanbul, Turkey.
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Blüher M. Vaspin in obesity and diabetes: pathophysiological and clinical significance. Endocrine 2012; 41:176-82. [PMID: 22139797 DOI: 10.1007/s12020-011-9572-0] [Citation(s) in RCA: 121] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2011] [Accepted: 11/19/2011] [Indexed: 01/06/2023]
Abstract
Vaspin (visceral adipose tissue-derived serpin; serpinA12) was originally identified as an adipokine, which is predominantly secreted from visceral adipose tissue in Otsuka Long-Evans Tokushima fatty (OLETF), an animal model of obesity and type 2 diabetes. Consistent with that higher vaspin serum concentrations and increased vaspin mRNA expression in human adipose tissue were found to be associated with obesity, insulin resistance, and type 2 diabetes in humans. However, the mechanisms how vaspin secretion may be linked to deterioration of glucose metabolism and insulin sensitivity are not entirely understood. Vaspin serum concentrations show a food intake-related diurnal variation. Vaspin is also expressed in the skin, hypothalamus, pancreatic islets, and stomach. Administration of vaspin to obese mice improves glucose tolerance, insulin sensitivity, and reduces food intake. Until now molecular target(s) of vaspin and its mode of action are unknown. Thus, identification of the proteases, which are inhibited by vaspin may lead to the development of novel strategies in the treatment of obesity, diabetes and insulin resistance. This review discusses the clinical relevance of vaspin in the pathophysiology of obesity and type 2 diabetes.
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Affiliation(s)
- Matthias Blüher
- Department of Medicine, University of Leipzig, Liebigstr. 20, 04103 Leipzig, Germany.
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