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Li M, Wan Y, Wei Z, Lin W. Comparison of the predictive value of TyG index and METS-IR for OSA combined with NAFLD: a retrospective observational study based on a physical examination population. BMC Gastroenterol 2025; 25:279. [PMID: 40259241 PMCID: PMC12013029 DOI: 10.1186/s12876-025-03856-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 04/04/2025] [Indexed: 04/23/2025] Open
Abstract
BACKGROUND Obstructive sleep apnoea (OSA), Non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR) are interlinked. The aim of our study was to investigate the predictive value of metabolic score for insulin resistance (METS-IR) and triglyceride-glucose(TyG) index in relation to OSA combined with NAFLD in physical examination population. METHODS This is a retrospective observational study. 329 physical examiners who attended the healthcare centre of the First Affiliated Hospital of Wenzhou Medical University for polysomnography and abdominal ultrasonography (or CT abdominal scanning) from September 2021 to July 2024. Subjects were categorized into two groups according to the presence or absence of combined NAFLD. Logistic regression analysis and restricted cubic spline model (RCS) were used to evaluate the relationship between TyG index and METS-IR and NAFLD. The predictive value of TyG index and METS-IR for NAFLD was determined by receiver operating characteristic curves (ROC curves). RESULTS A total of 329 subjects were analyzed. The prevalence of NAFLD increased with increasing TyG index (P for trend < 0.001), and METS-IR showed an increasing-decreasing-increasing trend with NAFLD risk (P for trend < 0.001). RCS analysis showed a dose-response relationship between NAFLD risk and METS-IR (p = 0.012) and a linear relationship with the TyG index (p = 0.078), with a significant increase in the risk of NAFLD when the METS-IR exceeded a threshold of 47.47 (OR = 1). Compared with TyG index (AUC = 0.775, 95% CI: 0.711-0.828), METS-IR (AUC = 0.778, 95% CI: 0.716-0.836) had a higher predictive value for NAFLD in the OSA physical examination population. CONCLUSIONS In the OSA population, TyG index and METS-IR had predictive value for the development of NAFLD, with METS-IR being superior to TyG index.
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Affiliation(s)
- Min Li
- First Clinical School of Medicine (School of Information and Engineering), Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yujing Wan
- First Clinical School of Medicine (School of Information and Engineering), Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ziyue Wei
- First Clinical School of Medicine (School of Information and Engineering), Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Weihong Lin
- Department of Healthcare Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Wenzhou Key Laboratory of Intelligent Prevention and Active Health for Aging-Related Chronic Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
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Liu Z, Huang J, Dai L, Yuan H, Jiang Y, Suo C, Jin L, Zhang T, Chen X. Steatotic Liver Disease Prevalence in China: A Population-Based Study and Meta-Analysis of 17.4 Million Individuals. Aliment Pharmacol Ther 2025; 61:1110-1122. [PMID: 40013739 DOI: 10.1111/apt.70051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/20/2024] [Accepted: 02/16/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND Steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), has emerged as a leading cause of chronic liver disease in China. AIMS We aimed to provide a comprehensive and updated description of SLD prevalence in China. METHODS We described the prevalence, subgroup distribution, and clinical characteristics of SLD in the Taizhou Study of Liver Diseases (T-SOLID). Additionally, we searched for studies reporting SLD prevalence in five databases. Eligible data were analysed using a generalised linear mixed model. Linear regression was applied to estimate the annual average percentage change (AAPC). RESULTS Of the 28,623 participants in T-SOLID, 30.8% were diagnosed with SLD, among which 83.8% were classified as MASLD. Prevalence of SLD increased from 22.1% in 2018 to 36.7% in 2021. The meta-analysis included 792 publications and 17,404,296 subjects. Nationwide, the pooled SLD prevalence rose from 23.8% (95% CI 21.9%-25.9%) during 2001-2010 to 27.9% (26.0%-29.8%) during 2016-2023 in the general population (AAPC = 2.56, p < 0.0001), equating to approximately 402.0 million cases. An increase in SLD prevalence was observed in subpopulations by region, sex, and age, and in high-risk groups. Northeast China had the highest prevalence (35.0%). Males had a higher prevalence rate than females (35.0% vs. 20.6%). SLD prevalence increased with age, ranging from 8.1% in children and adolescents to 31.8% in the elderly. Meta-regression identified calendar period, age, sex, geographical area, and residence area as significant determinants of SLD prevalence. CONCLUSION The ubiquitously rising prevalence of SLD in Chinese populations underscores the urgent need for targeted public health interventions.
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Affiliation(s)
- Zhenqiu Liu
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Jiayi Huang
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Luojia Dai
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Huangbo Yuan
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Yanfeng Jiang
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Chen Suo
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Li Jin
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tiejun Zhang
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Xingdong Chen
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University, Shanghai, China
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3
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Liu Z, Jiang Y, Suo C, Yuan H, Yuan Z, Zhang T, Jin L, Chen X. Cohort Profile: Taizhou Study of Liver Diseases (T-SOLID). Int J Epidemiol 2025; 54:dyaf030. [PMID: 40199566 DOI: 10.1093/ije/dyaf030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 03/07/2025] [Indexed: 04/10/2025] Open
Affiliation(s)
- Zhenqiu Liu
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Yanfeng Jiang
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Chen Suo
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Huangbo Yuan
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Ziyu Yuan
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tiejun Zhang
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Li Jin
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University, Shanghai, China
| | - Xingdong Chen
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University, Shanghai, China
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Mei XL, Wu SY, Wu SL, Luo XL, Huang SX, Liu R, Qiang Z. Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism. World J Hepatol 2024; 16:1051-1066. [PMID: 39086531 PMCID: PMC11287615 DOI: 10.4254/wjh.v16.i7.1051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/23/2024] [Accepted: 06/11/2024] [Indexed: 07/26/2024] Open
Abstract
BACKGROUND The modified Xiaoyao San (MXS) formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer, which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival. However, the molecular mechanisms underlying that remain unclear. AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury, steatosis and inflammation. METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis (NASH) model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes. Liver tissues were collected for western blotting and immunohistochemistry (IHC) assays. Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining. The serum samples were collected for biochemical assays and NMR-based metabonomics analysis. The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH. RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation, inflammation and hepatic fibrosis in the pathogenesis of NASH. The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis. Mechanistically, we found that MXS protected against NASH by attenuating the sex hormone-related metabolism, especially the metabolism of male hormones. CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones. Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.
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Affiliation(s)
- Xiao-Li Mei
- Department of Pharmacology and Toxicology, Sichuan-Chongqing Joint Key Laboratory of New Chinese Medicine Creation Laboratory, Chongqing Academy of Chinese Materia Medica, Chongqing 400061, China
| | - Shu-Yi Wu
- College of Chinese Medicine, Chongqing College of Traditional Chinses Medicine, Chongqing 402760, China
| | - Si-Lan Wu
- Department of Pharmacology and Toxicology, Sichuan-Chongqing Joint Key Laboratory of New Chinese Medicine Creation Laboratory, Chongqing Academy of Chinese Materia Medica, Chongqing 400061, China
| | - Xiao-Lin Luo
- Department of Pharmacology and Toxicology, Sichuan-Chongqing Joint Key Laboratory of New Chinese Medicine Creation Laboratory, Chongqing Academy of Chinese Materia Medica, Chongqing 400061, China
| | - Si-Xing Huang
- Department of Pharmacology and Toxicology, Sichuan-Chongqing Joint Key Laboratory of New Chinese Medicine Creation Laboratory, Chongqing Academy of Chinese Materia Medica, Chongqing 400061, China
| | - Rui Liu
- Department of Oncology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Zhe Qiang
- Department of Pharmacology and Toxicology, Sichuan-Chongqing Joint Key Laboratory of New Chinese Medicine Creation Laboratory, Chongqing Academy of Chinese Materia Medica, Chongqing 400061, China
- College of Chinese Medicine, Chongqing College of Traditional Chinses Medicine, Chongqing 402760, China
- College of Pharmacy, Chongqing Medical University, Chongqing 400010, China.
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Liu Q, Han M, Li M, Huang X, Feng R, Li W, Chen J, He H, Zheng W, Hu Z, Du S, Ye W. Shift in prevalence and systemic inflammation levels from NAFLD to MAFLD: a population-based cross-sectional study. Lipids Health Dis 2023; 22:185. [PMID: 37898739 PMCID: PMC10613356 DOI: 10.1186/s12944-023-01947-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 10/16/2023] [Indexed: 10/30/2023] Open
Abstract
BACKGROUND Variations in the prevalence and systemic inflammatory (SI) status between non-alcoholic fatty liver disease (NAFLD) and newly defined metabolic dysfunction-associated fatty liver disease (MAFLD) have only been reported by few studies. Hence, this study aimed to compile data on the prevalence and the systemic inflammation levels of MAFLD and NAFLD in a general population from Southeast China was summarized to explore the potential effect of the transformation of disease definition. METHODS A total of 6718 general population participants aged 35-75 were enrolled. Logistic regression and restricted cubic spline (RCS) models were used to examine the relationship between 15 SI indicators and NAFLD and MAFLD. The predicted values of MAFLD and NAFLD were analyzed using the receiver operating characteristic (ROC) curve. RESULTS The prevalence of MAFLD and NAFLD was 34.7% and 32.4%, respectively. Their overlapping rate was 89.7%, while only 8.3% and 1.9% of participants were MAFLD-only and NAFLD-only. Among three FLD groups, the MAFLD-only group had the highest levels of 8 SI indicators, including CRP, WBC, LYMPH, NEUT, MONO, ALB, NLR, and SIRI. The non-FLD group had the lower levels of all 15 SI indicators compared with all FLD subgroups. The odds ratios (ORs) of 10 SI indicators were significant in both multivariable-adjusted logistic regression and RCS analyses of MAFLD or NAFLD, including CRP, WBC, LYMPH, NEUT, MONO, ALB, PLR, LMR, ALI and CA. ROC analysis showed that the AUC values of all SI were lower than 0.7 in both MAFLD and NAFLD. CONCLUSIONS MAFLD could cover more FLD than NAFLD, and the MAFLD-only group had a more severe inflammation status, whereas the NAFLD-only exhibited lower levels. Moreover, there was not a high AUC and a high sensitivity of SI indicators, suggesting that SI indicators are not good indicators to diagnose NAFLD/MAFLD.
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Affiliation(s)
- Qingdan Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, University Town, No 1, Xue Yuan Road, Fuzhou, 350108, Fujian, China
| | - Meilan Han
- Department of Ultrasonography, Fuqing Hospital, Fuqing, China
| | - Meilan Li
- Infection Control Department, The Fifth Hospital of Fuqing City, Fuqing, China
| | - Xiaoyin Huang
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, University Town, No 1, Xue Yuan Road, Fuzhou, 350108, Fujian, China
| | - Ruimei Feng
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, University Town, No 1, Xue Yuan Road, Fuzhou, 350108, Fujian, China
| | - Wanxin Li
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, University Town, No 1, Xue Yuan Road, Fuzhou, 350108, Fujian, China
| | - Jun Chen
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, University Town, No 1, Xue Yuan Road, Fuzhou, 350108, Fujian, China
| | - Haiying He
- Department of Ultrasonography, Fuqing Hospital, Fuqing, China
| | - Wenxin Zheng
- Infection Control Department, The Fifth Hospital of Fuqing City, Fuqing, China
| | - Zhijian Hu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, University Town, No 1, Xue Yuan Road, Fuzhou, 350108, Fujian, China
| | - Shanshan Du
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, University Town, No 1, Xue Yuan Road, Fuzhou, 350108, Fujian, China.
| | - Weimin Ye
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, University Town, No 1, Xue Yuan Road, Fuzhou, 350108, Fujian, China.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Dai JJ, Zhang YF, Zhang ZH. Global trends and hotspots of treatment for nonalcoholic fatty liver disease: A bibliometric and visualization analysis (2010-2023). World J Gastroenterol 2023; 29:5339-5360. [PMID: 37899789 PMCID: PMC10600806 DOI: 10.3748/wjg.v29.i37.5339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/26/2023] [Accepted: 09/04/2023] [Indexed: 09/25/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is chronic, with its progression leading to liver fibrosis and end-stage cirrhosis. Although NAFLD is increasingly common, no treatment guideline has been established. Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD. An up-to-date overview on the knowledge structure of NAFLD through bibliometrics, focusing on research hotspots, is necessary to reveal the rational and timely directions of development in this field. AIM To research the latest literature and determine the current trends in treatment for NAFLD. METHODS Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database, from 2010 to 2023. VOSviewers, CiteSpace, and R package "bibliometrix" were used to conduct this bibliometric analysis. The key information was extracted, and the results of the cluster analysis were based on network data for generating and investigating maps for country, institution, journal, and author. Historiography analysis, bursts and cluster analysis, co-occurrence analysis, and trend topic revealed the knowledge structure and research hotspots in this field. GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization. RESULTS In total, 10829 articles from 120 countries (led by China and the United States) and 8785 institutions were included. The number of publications related to treatment for NAFLD increased annually. While China produced the most publications, the United States was the most cited country, and the United Kingdom collaborated the most from an international standpoint. The University of California-San Diego, Shanghai Jiao Tong University, and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions. The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals, and Hepatology was the most cited and co-cited journal. Sanyal AJ was the most cited author, the most co-cited author was Younossi ZM, and the most influential author was Loomba R. The most studied topics included the epidemiology and mechanism of NAFLD, the development of accurate diagnosis, the precise management of patients with NAFLD, and the associated metabolic comorbidities. The major cluster topics were "emerging drug," "glucagon-like peptide-1 receptor agonist," "metabolic dysfunction-associated fatty liver disease," "gut microbiota," and "glucose metabolism." CONCLUSION The bibliometric study identified recent research frontiers and hot directions, which can provide a valuable reference for scholars researching treatments for NAFLD.
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Affiliation(s)
- Jin-Jin Dai
- Department of Infectious Diseases, Suzhou Hospital of Anhui Medical University, Suzhou 234000, Anhui Province, China
- Department of Infectious Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Ya-Fei Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Zhen-Hua Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
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Zhang S, Li H, Meng G, Zhang Q, Liu L, Wu H, Gu Y, Zhang T, Wang X, Zhang J, Dong J, Zheng X, Cao Z, Zhang X, Dong X, Sun S, Wang X, Zhou M, Jia Q, Song K, Borné Y, Sonestedt E, Qi L, Niu K. Added sugar intake and its forms and sources in relation to risk of non-alcoholic fatty liver disease: results from the Tianjin Chronic Low-grade Systemic Inflammation and Health cohort study. Br J Nutr 2023; 129:2094-2101. [PMID: 36156191 DOI: 10.1017/s000711452200277x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid v. solid) and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15 538 participants, free of NAFLD, other liver diseases, CVD, cancer or diabetes at baseline (2013-2018 years). Added sugar intake was estimated from a validated 100-item FFQ. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazard ratios (HR) and corresponding 95 % CI for NAFLD risk with added sugar intake. During a median follow-up of 4·2 years, 3476 incident NAFLD cases were documented. After adjusting for age, sex, BMI and its change from baseline to follow-up, lifestyle factors, personal and family medical history and overall diet quality, the multivariable HR of NAFLD risk were 1·18 (95 % CI 1·06, 1·32) for total added sugars, 1·20 (95 % CI 1·08, 1·33) for liquid added sugars and 0·96 (95 % CI 0·86, 1·07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.
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Affiliation(s)
- Shunming Zhang
- Nutrition and Radiation Epidemiology Research Center, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People's Republic of China
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
- Nutritional Epidemiology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden
| | - Huiping Li
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Ge Meng
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Qing Zhang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Li Liu
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Hongmei Wu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Yeqing Gu
- Nutrition and Radiation Epidemiology Research Center, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People's Republic of China
| | - Tingjing Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Xuena Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Juanjuan Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Jun Dong
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Xiaoxi Zheng
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Zhixia Cao
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Xu Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Xinrong Dong
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
| | - Shaomei Sun
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Xing Wang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Ming Zhou
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Qiyu Jia
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Kun Song
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
| | - Yan Borné
- Nutritional Epidemiology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden
| | - Emily Sonestedt
- Nutritional Epidemiology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden
| | - Lu Qi
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Kaijun Niu
- Nutrition and Radiation Epidemiology Research Center, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People's Republic of China
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People's Republic of China
- Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, People's Republic of China
- Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin, People's Republic of China
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Li H, Shi Z, Chen X, Wang J, Ding J, Geng S, Sheng X, Shi S. Relationship Between Six Insulin Resistance Surrogates and Nonalcoholic Fatty Liver Disease Among Older Adults: A Cross-Sectional Study. Diabetes Metab Syndr Obes 2023; 16:1685-1696. [PMID: 37309507 PMCID: PMC10257913 DOI: 10.2147/dmso.s409983] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 05/31/2023] [Indexed: 06/14/2023] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) represents a large and growing public health problem. Insulin resistance (IR) plays a crucial role in the pathogenesis of NAFLD. The aim of this study was to determine the association of triglyceride-glucose (TyG) index, TyG index with body mass index (TyG-BMI), lipid accumulation product (LAP), visceral adiposity index (VAI), triglycerides/high-density lipoprotein cholesterol ratio (TG/HDL-c) and metabolic score for IR (METS-IR) with NAFLD in older adults and to compare the discriminatory abilities of these six IR surrogates for NAFLD. Methods This cross-sectional study included 72,225 subjects aged ≥60 years living in Xinzheng, Henan Province, from January 2021 to December 2021. The data were collected from the annual health examination dataset. Logistic regression models were used to examine the relationships between the six indicators and NAFLD risk. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory ability of different IR surrogates for NAFLD under the influence of potential risk factors. Results After adjusting for multiple covariates, compared with the first quintile, the odds ratios (ORs) and 95% confidence intervals (CIs) of the highest quintiles of TyG-BMI were the most obvious (OR:43.02, 95% CI:38.89-47.72), followed by the METS-IR (OR:34.49, 95% CI:31.41-37.95). Restricted cubic spline analysis reported that there were non-linear positive association and dose-response relationship between 6 IR surrogates and NAFLD risk. Compared with other IR-related indicators (LAP, TyG, TG/HDL-c and VAI), TyG-BMI showed the highest AUC (AUC:0.8059;95% CI:0.8025-0.8094). Additionally, METS-IR also had a high predictive performance for NAFLD, and the AUC was greater than 0.75 (AUC:0.7959;95% CI:0.7923-0.7994). Conclusion TyG-BMI and METS-IR had pronounced discrimination ability to NAFLD, which are recommended as complementary markers for the assessment of NAFLD risk both in clinic and in future epidemiological studies.
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Affiliation(s)
- Haojie Li
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
| | - Zhan Shi
- Department of Pharmacy, Zhengzhou People’s Hospital, Zhengzhou, Henan, People’s Republic of China
| | - Xuejiao Chen
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
| | - Junjie Wang
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
| | - Jiacheng Ding
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
| | - Shuoji Geng
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
| | - Xinyuan Sheng
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
| | - Songhe Shi
- Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
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9
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Zhang S, Yan Y, Meng G, Zhang Q, Liu L, Wu H, Gu Y, Wang X, Zhang J, Sun S, Wang X, Zhou M, Jia Q, Song K, Borné Y, Qi L, Chen YM, Niu K. Protein foods from animal sources and risk of nonalcoholic fatty liver disease in representative cohorts from North and South China. J Intern Med 2023; 293:340-353. [PMID: 36433820 DOI: 10.1111/joim.13586] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Emerging evidence suggests that animal protein foods may increase the risk of nonalcoholic fatty liver disease (NAFLD). We therefore examined the NAFLD risk reduction related to substituting plant protein foods for animal protein foods. METHODS The cohort in North China included 14,541 participants from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) study, and the cohort in South China included 1297 participants from the Guangzhou Nutrition and Health Study (GNHS). Dietary intake was assessed using validated food frequency questionnaires. NAFLD was ascertained by abdominal ultrasound. The Cox model was used to fit the substitution analysis. RESULTS In the TCLSIH cohort, when replacing one type of animal protein food (eggs, processed meat, unprocessed red meat, poultry, and fish) with an equivalent serving of plant protein foods (nuts, legumes, and whole grains), the replacement of animal protein foods with whole grains showed the strongest benefit; substituting one serving per day of whole grains for an equal amount of eggs (hazard ratio [HR] = 0.89; 95% confidence interval [CI]: 0.79, 1.00), processed meat (HR = 0.76; 95% CI: 0.64, 0.91), unprocessed red meat (HR = 0.90; 95% CI: 0.81, 1.00), poultry (HR = 0.81; 95% CI: 0.72, 0.92), or fish (HR = 0.87; 95% CI: 0.78, 0.97) was associated with a lower risk of NAFLD. In both the TCLSIH and GNHS cohorts, replacing poultry with fish, nuts, legumes, or whole grains was associated with a lower risk of NAFLD. When different numbers of protein foods were simultaneously replaced, the risk reduction of NAFLD was stronger. CONCLUSIONS Our findings suggest that replacing animal protein foods with plant protein foods is related to a significant reduction in NAFLD risk.
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Affiliation(s)
- Shunming Zhang
- School of Public Health of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.,Nutritional Epidemiology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden
| | - Yan Yan
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Ge Meng
- School of Public Health of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Qing Zhang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Li Liu
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Hongmei Wu
- School of Public Health of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yeqing Gu
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Xuena Wang
- School of Public Health of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Juanjuan Zhang
- School of Public Health of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Shaomei Sun
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Xing Wang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Zhou
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiyu Jia
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Kun Song
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Yan Borné
- Nutritional Epidemiology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden
| | - Lu Qi
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Yu-Ming Chen
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Kaijun Niu
- School of Public Health of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
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10
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Liu H, Qi J, Yang J, Liu F, Li X, Yin P, Wang L, Liang Z, Wei L, Rao H, Zhou M. Burden of liver complications related to non-alcoholic fatty liver disease in China from 2005 to 2019: Observations from the Global Burden of Disease Study, 2019. Diabetes Obes Metab 2023; 25 Suppl 1:43-52. [PMID: 36781698 DOI: 10.1111/dom.15010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/28/2023] [Accepted: 02/08/2023] [Indexed: 02/15/2023]
Abstract
AIM To assess the burden of liver complications related to non-alcoholic fatty liver disease (LC-NAFLD) from 2005 to 2019 in China. MATERIALS AND METHODS We used data from the Global Burden of Disease, Injuries, and Risk Factors Study, 2019, to present contemporary and varying profiles of China's LC-NAFLD burden. The Joinpoint Regression model and Gaussian process regression were, respectively, used to estimate the annual percentage change in prevalence rates and disability-adjusted life-year (DALY) rates, and the relationship between the sociodemographic index (SDI) and age-standardized rates of LC-NAFLD. RESULTS In 2019, China had 293.42 million (95% uncertainty interval [UI]: 263.69-328.44) LC-NAFLD cases with a prevalence rate and DALYs of 20.63 (95% UI: 23.09-18.54) per 1000 people and 591.03 thousand (95% UI: 451.25-737.33), respectively. North China had the highest prevalence but the lowest DALYs of LC-NAFLD, whereas Southwest China had the lowest prevalence but the highest DALYs. LC-NAFLD were more common in men than in women (male: female ratio, 1.27) in 2019. From 2005 to 2019, the prevalence of NAFLD cases increased by 68.32% (from 174.32 million in 2005 to 293.42 million in 2019), mainly because of an age-specific prevalence rate increase. CONCLUSION The LC-NAFLD burden in China is substantial and has increased markedly over the past 15 years. Effective measures for low SDI regions and men are needed to address the rapidly increasing NAFLD burden.
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Affiliation(s)
- Huixin Liu
- Department of Clinical Epidemiology and Biostatistics, Peking University People's Hospital, Beijing, China
| | - Jinlei Qi
- National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Jia Yang
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Feng Liu
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Xiaohe Li
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Peng Yin
- National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lijun Wang
- National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Zhisheng Liang
- Department of Global Health, School of Public Health, Peking University, Beijing, China
| | - Lai Wei
- Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Huiying Rao
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Maigeng Zhou
- National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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11
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Wong VWS, Tak WY, Goh GBB, Cheng PN, Lawitz EJ, Younossi ZM, Vuppalanchi R, Younes Z, Alkhouri N, Wang L, Liu J, Kersey K, Myers RP, Harrison SA, Goodman Z, Trauner M, Romero-Gomez M, Anstee QM, Nguyen MH, Okanoue T. Performance of Noninvasive Tests of Fibrosis Among Asians, Hispanic, and non-Hispanic Whites in the STELLAR Trials. Clin Gastroenterol Hepatol 2023; 21:90-102.e6. [PMID: 35074532 DOI: 10.1016/j.cgh.2022.01.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 12/16/2021] [Accepted: 01/11/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The effect of race on routinely available noninvasive tests of fibrosis is incompletely understood. This study evaluated the performance of noninvasive tests among white and Asian patients in the STELLAR trials (NCT03053050 and NCT03053063), which evaluated selonsertib in patients with advanced (F3-F4) fibrosis due to nonalcoholic steatohepatitis (NASH). METHODS Baseline liver biopsies were centrally read using the NASH Clinical Research Network system, and 4 noninvasive tests (Nonalcoholic fatty liver disease fibrosis score [NFS], Fibrosis-4 index [FIB-4], Enhanced Liver Fibrosis test [ELF], and liver stiffness by vibration-controlled transient elastography) were measured. The performance of these tests to discriminate advanced fibrosis was evaluated using areas under the receiver operating characteristics curves with 5-fold cross-validation repeated 100 times. RESULTS Among 3207 patients screened with evaluable liver histology, 2281 were whites and 762 were Asians. Seventy-two percent of whites and 67% of Asians had advanced fibrosis. The areas under the receiver operating characteristics curves of the noninvasive tests for advanced fibrosis were similar in whites and Asians: 0.73 and 0.75 for NFS, 0.78 and 0.80 for FIB-4, 0.79 and 0.81 for ELF, and 0.80 and 0.83 for liver stiffness, respectively. At the published cutoffs, the tests had similar sensitivities and specificities in the 2 groups. However, the sensitivities of NFS, FIB-4, and ELF were low in both white and Asian patients younger than 40 years. CONCLUSIONS In the global phase III STELLAR trials, the diagnostic performance of routinely available noninvasive tests for the detection of advanced fibrosis due to NASH was acceptable and similar between white and Asian patients.
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Affiliation(s)
- Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
| | - Won Young Tak
- School of Medicine Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - George Boon Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Eric J Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, Texas
| | | | | | | | | | - Lulu Wang
- Gilead Sciences, Inc, Foster City, California
| | - Jialuo Liu
- Gilead Sciences, Inc, Foster City, California
| | | | | | | | | | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | | | - Quentin M Anstee
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, UK; Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
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12
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Inverse Association of Fruit and Vegetable Consumption with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus. Nutrients 2022; 14:nu14214559. [PMID: 36364821 PMCID: PMC9657780 DOI: 10.3390/nu14214559] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/14/2022] [Accepted: 10/17/2022] [Indexed: 11/17/2022] Open
Abstract
We aimed to investigate the association of fruit and vegetable consumption with nonalcoholic fatty liver disease (NAFLD) in Chinese patients with type 2 diabetes mellitus (T2DM). This cross-sectional study included 2667 Chinese patients with T2DM aged 18 to 76 years from March 2017 to October 2021. Dietary intake was assessed using a food frequency questionnaire, and prevalent NAFLD was diagnosed with abdominal ultrasonography. High fruit−vegetable consumption was determined using ≥500 g/day consumption of both fruit and vegetable, and both fruit and vegetable consumption were divided into three categories of <200 g/day (low), 200−400 g/day (median) and >400 g (high). The primary outcome measurement was multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the prevalence of NAFLD in relation to the highest fruit and (or) vegetable intake compared with the lowest. Secondary analyses were conducted to assess the effects of either fruit or vegetable intake on the fatty liver index (FLI) using multivariable linear regressions. There were 1694 men and 973 women in this study, and 1445 (54.06%) participants had prevalent NAFLD. Patients with high fruit−vegetable intake had a lower prevalence of NAFLD than those with low fruit−vegetable intake (52.04% vs. 56.48%), but this difference was not statistically significant (p = 0.065). Vegetable intake had a significantly inverse association with NAFLD (OR: 0.68, 95% CI: 0.52−0.90), but this association was not pronounced with fruit intake (OR: 1.23, 95% CI: 0.89−1.69) or fruit−vegetable intake (OR: 0.90, 95% CI: 0.73−1.10). Additional analyses showed that an increase in vegetable intake was linearly associated with a significant reduction in FLI (β: −1.028, 95% CI: −1.836, −0.219). In conclusion, higher vegetable consumption was associated with lower odds of NAFLD in Chinese patients with T2DM, which suggested that increased vegetable intake might protect patients with diabetes against NAFLD.
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13
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Lv J, Xing C, Chen Y, Bian H, Lv N, Wang Z, Liu M, Su L. The STING in Non-Alcoholic Fatty Liver Diseases: Potential Therapeutic Targets in Inflammation-Carcinogenesis Pathway. Pharmaceuticals (Basel) 2022; 15:1241. [PMID: 36297353 PMCID: PMC9611148 DOI: 10.3390/ph15101241] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/27/2022] [Accepted: 09/28/2022] [Indexed: 11/25/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), an important chronic disease, is one of the major causes of high mortality and creates a substantial financial burden worldwide. The various immune cells in the liver, including macrophages, NK cells, dendritic cells, and the neutrophils involved in the innate immune response, trigger inflammation after recognizing the damage signaled from infection or injured cells and tissues. The stimulator of interferon genes (STING) is a critical molecule that binds to the cyclic dinucleotides (CDNs) generated by the cyclic GMP-AMP synthase (cGAS) to initiate the innate immune response against infection. Previous studies have demonstrated that the cGAS-STING pathway plays a critical role in inflammatory, auto-immune, and anti-viral immune responses. Recently, studies have focused on the role of STING in liver diseases, the results implying that alterations in its activity may be involved in the pathogenesis of liver disorders. Here, we summarize the function of STING in the development of NAFLD and present the current inhibitors and agonists targeting STING.
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Affiliation(s)
- Juan Lv
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
| | - Chunlei Xing
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
| | - Yuhong Chen
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
- School of Pharmacy, Bengbu Medical College, Bengbu 233030, China
| | - Huihui Bian
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
| | - Nanning Lv
- Lianyungang Second People’s Hospital, Lianyungang 222002, China
| | - Zhibin Wang
- Department of Critical Care Medicine, School of Anesthesiology, Naval Medical University, Shanghai 200020, China
- School of Pharmacy, Naval Medical University, Shanghai 200433, China
| | - Mingming Liu
- Lianyungang Second People’s Hospital, Lianyungang 222002, China
| | - Li Su
- Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
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14
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Zhang S, Meng G, Zhang Q, Liu L, Wu H, Gu Y, Wang Y, Zhang T, Wang X, Zhang J, Sun S, Wang X, Zhou M, Jia Q, Song K, Wang Y, Qi L, Niu K. Inflammatory potential of diet and risk of nonalcoholic fatty liver disease: a prospective cohort study. Eur J Clin Nutr 2022; 76:1125-1132. [PMID: 35079162 DOI: 10.1038/s41430-022-01069-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 12/14/2021] [Accepted: 01/05/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND/OBJECTIVES Diet is an important factor that can exacerbate or ameliorate chronic inflammation, which has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, no prospective study has yet investigated the relation between the inflammatory potential of diet and NAFLD. The aim of this study was to investigate the association between the inflammatory potential of the diet and the risk of NAFLD. SUBJECT/METHODS The study included 12,877 participants aged over 18 years (mean [standard deviation]: 39.4 [11.5] years). Dietary intake was assessed at baseline through food frequency questionnaires. Using white blood cell count as the inflammatory marker, we newly created a dietary inflammatory potential score by reduced rank regression and stepwise linear regression. NAFLD was identified by abdominal ultrasound during yearly health checkups. Cox proportional hazards regression models were used to estimate the association between the dietary inflammatory potential score and the risk of NAFLD. RESULTS During a median follow-up period of 4.2 years, 2744 first incident cases of NAFLD occurred. After adjustment for potential confounders, the multivariable hazards ratios (95% confidence intervals) for NAFLD across increasing quartiles of the dietary inflammatory potential score were 1.00 (reference), 1.01 (0.90, 1.13), 1.15 (1.03, 1.29), and 1.26 (1.13, 1.41), with P for trend <0.0001. This positive association appeared greater in men than in women (P for interaction = 0.02). CONCLUSIONS Our results indicate that a dietary pattern with high inflammatory potential is associated with a higher risk of NAFLD. Such findings provide the support that inflammation may be a potential mechanism linking diet to the risk of NAFLD.
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Affiliation(s)
- Shunming Zhang
- Nutrition and Radiation Epidemiology Research Center, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.,Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden
| | - Ge Meng
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Qing Zhang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Li Liu
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Hongmei Wu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yeqing Gu
- Nutrition and Radiation Epidemiology Research Center, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Yawen Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Tingjing Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xuena Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Juanjuan Zhang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Shaomei Sun
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Xing Wang
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Zhou
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiyu Jia
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Kun Song
- Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Yaogang Wang
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China
| | - Lu Qi
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA. .,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Kaijun Niu
- Nutrition and Radiation Epidemiology Research Center, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. .,Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China. .,Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China. .,Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China. .,Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin, China.
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15
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Chen Y, Zhang P, Lv S, Su X, Du Y, Xu C, Jin Z. Ectopic fat deposition and its related abnormalities of lipid metabolism followed by nonalcoholic fatty pancreas. Endosc Ultrasound 2022; 11:407-413. [PMID: 35848656 DOI: 10.4103/eus-d-21-00167] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background and Objectives The positive energy balance between caloric intake and caloric output increasing storage of triglycerides (TG) in adipocytes has made nonalcoholic fatty liver disease (NAFLD) one of the major public health problems in China. Excessive lipid deposition in the pancreas is referred to as nonalcoholic fatty pancreas disease (NAFPD). Early assessment of pancreatic fat infiltration will have an increasing role in the clinical management of the metabolic dysregulation and prevention pancreatic complications. Subjects and Methods We retrospectively collected data of inpatients with NAFPD from EUS database between September 2012 and August 2020 at our endoscopic center. The prevalence of NAFPD and factors associated with its development were statistically analyzed. The echogenicity of the pancreas was compared to that of the left renal cortex during the EUS examination by using an existing criterion. Results Four thousand, seven hundred and four consecutive individuals underwent EUS were enrolled. The prevalence of NAFPD was 1.2% (57/4704) . Factors independently associated with NAFPD on multivariate analysis were increasing TG (odds ratios [OR] 4.65, P = 0.014), NAFLD (OR 16.76, P = 0.005) and decreasing apolipoprotein A-1 (OR 0.002, P = 0.0127). We found no association between NAFPD and age, sex, total cholesterol or hypertension. Conclusions We found a meaningful relationship between NAFLD, dyslipidemia, and NAFPD in Chinese. We hypothesized that NAFPD was strongly correlated with ectopic fat deposition and its related abnormalities of lipid metabolism. Early diagnosis of NAFLD provides opportunities to control the progression of NAFPD.
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Affiliation(s)
- Yan Chen
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Pingping Zhang
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Shunli Lv
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xiaoju Su
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Yiqi Du
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Can Xu
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Zhendong Jin
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
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16
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Wang C, Yan J, Zhang S, Xie Y, Nie Y, Chen Z, Xu S. Screening New Blood Indicators for Non-alcoholic Fatty Liver Disease (NAFLD) Diagnosis of Chinese Based on Machine Learning. Front Med (Lausanne) 2022; 9:771219. [PMID: 35755070 PMCID: PMC9218755 DOI: 10.3389/fmed.2022.771219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 04/28/2022] [Indexed: 11/13/2022] Open
Abstract
Background The prevalence of NAFLD is increasing annually. The early diagnosis and control are crucial for the disease. Currently, metabolic indicators are always used clinically as an auxiliary diagnosis of NAFLD. However, the prevalence of NAFLD is not only increased in obese/metabolic-disordered populations. NAFLD patients with thin body are also increasing. Only using metabolic indicators to assist in the diagnosis of NAFLD may have some deficiencies. Continue to develop more clinical auxiliary diagnostic indicators is pressing. Methods Machine learning methods are applied to capture risk factors for NAFLD in 365 adults from Zhejiang Province. Predictive models are constructed for NAFLD using fibrinolytic indicators and metabolic indicators as predictors respectively. Then the predictive effects are compared; ELISA kits were used to detect the blood indicators of non-NAFLD and NAFLD patients and compare the differences. Results The prediction accuracy for NAFLD based on fibrinolytic indicators [Tissue Plasminogen Activator (TPA), Plasminogen Activator Inhibitor-1 (PAI-1)] is higher than that based on metabolic indicators. TPA and PAI-1 are more suitable than metabolic indicators to be selected to predict NAFLD. Conclusions The fibrinolytic indicators have a stronger association with NAFLD than metabolic indicators. We should attach more importance to TPA and PAI-1, in addition to TC, HDL-C, LDL-C, and ALT/AST, when conducting blood tests to assess NAFLD.
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Affiliation(s)
- Cheng Wang
- Applied Math Department, China Jiliang University, Hangzhou, China
| | - Junbin Yan
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
- Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou, China
| | - Shuo Zhang
- Gastroenterology Department, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, China
| | - Yiwen Xie
- Department of General Practice, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, China
| | - Yunmeng Nie
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhiyun Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
- Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou, China
- *Correspondence: Zhiyun Chen
| | - Sumei Xu
- Department of General Practice, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, China
- Sumei Xu
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17
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Leung H, Long X, Ni Y, Qian L, Nychas E, Siliceo SL, Pohl D, Hanhineva K, Liu Y, Xu A, Nielsen HB, Belda E, Clément K, Loomba R, Li H, Jia W, Panagiotou G. Risk assessment with gut microbiome and metabolite markers in NAFLD development. Sci Transl Med 2022; 14:eabk0855. [PMID: 35675435 PMCID: PMC9746350 DOI: 10.1126/scitranslmed.abk0855] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.
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Affiliation(s)
- Howell Leung
- Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology–Hans Knöll Institute, Beutenbergstraße 11A, 07745 Jena, Germany
| | - Xiaoxue Long
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, 200233 Shanghai, China
| | - Yueqiong Ni
- Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology–Hans Knöll Institute, Beutenbergstraße 11A, 07745 Jena, Germany.,Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, 200233 Shanghai, China.,Corresponding author. (Y.N.); (H.L.); (W.J.); (G.P.)
| | - Lingling Qian
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, 200233 Shanghai, China
| | - Emmanouil Nychas
- Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology–Hans Knöll Institute, Beutenbergstraße 11A, 07745 Jena, Germany
| | - Sara Leal Siliceo
- Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology–Hans Knöll Institute, Beutenbergstraße 11A, 07745 Jena, Germany
| | - Dennis Pohl
- Clinical Microbiomics, Fruebjergvej 3, 2100 Copenhagen, Denmark.,Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, Building 220, 2800 Kgs. Lyngby, Denmark
| | - Kati Hanhineva
- Department of Life Technologies, Food Chemistry and Food Development Unit, University of Turku, 20014 Turku, Finland.,Department of Biology and Biological Engineering, Division of Food and Nutrition Science, Chalmers University of Technology, 412 96 Gothenburg, Sweden.,School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland
| | - Yan Liu
- The State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China.,Department of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Aimin Xu
- The State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China.,Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.,Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China
| | | | - Eugeni Belda
- Sorbonne Université, INSERM, NutriOmics Research Unit, Nutrition Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, 75013 Paris, France
| | - Karine Clément
- Sorbonne Université, INSERM, NutriOmics Research Unit, Nutrition Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, 75013 Paris, France
| | - Rohit Loomba
- NAFLD Research Center, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
| | - Huating Li
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, 200233 Shanghai, China.,Corresponding author. (Y.N.); (H.L.); (W.J.); (G.P.)
| | - Weiping Jia
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, 200233 Shanghai, China.,Corresponding author. (Y.N.); (H.L.); (W.J.); (G.P.)
| | - Gianni Panagiotou
- Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology–Hans Knöll Institute, Beutenbergstraße 11A, 07745 Jena, Germany.,The State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China.,Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.,Corresponding author. (Y.N.); (H.L.); (W.J.); (G.P.)
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18
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Zhang X, Huo Z, Luan H, Huang Y, Shen Y, Sheng L, Liang J, Wu F. Scutellarin ameliorates hepatic lipid accumulation by enhancing autophagy and suppressing IRE1α/XBP1 pathway. Phytother Res 2021; 36:433-447. [PMID: 34859513 DOI: 10.1002/ptr.7344] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 09/29/2021] [Accepted: 11/01/2021] [Indexed: 12/29/2022]
Abstract
Nonalcoholic fatty liver disease is the most prevalent liver disease characterized by excessive lipid accumulation in hepatocytes. Endoplasmic reticulum (ER) stress and autophagy play an important role in lipid accumulation. In this study, scutellarin (Scu) was examined in palmitic acid-treated HepG2 cells and C57/BL6 mice fed a high-fat diet (HFD). Scu reduced intracellular lipid content and inhibited sterol regulatory element binding protein-1c (SREBP-1c)-mediated lipid synthesis and fatty acid translocase-mediated lipid uptake in HepG2 cells. Additionally, Scu restored impaired autophagy and inhibited excessive activation of ER stress in vivo and in vitro. Moreover, Scu upregulated forkhead box O transcription factor 1-mediated autophagy by inhibiting inositol-requiring enzyme 1α (IRE1α)/X-box-binding protein 1 (XBP1) branch activation, while XBP1s overexpression exacerbated the lipid accumulation and impaired autophagy in HepG2 cells and also weakened the positive effects of Scu. Furthermore, Scu attenuated ER stress by activating autophagy, ultimately downregulating SREBP-1c-mediated lipid synthesis, and autophagy inhibitors offset these beneficial effects. Scu inhibited the crosstalk between autophagy and ER stress and downregulated saturated fatty acid-induced lipid accumulation in hepatocytes. These findings demonstrate that Scu ameliorates hepatic lipid accumulation by enhancing autophagy and suppressing ER stress via the IRE1α/XBP1 pathway.
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Affiliation(s)
- Xueying Zhang
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Zhaojiong Huo
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Huiling Luan
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Yihai Huang
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Yanhui Shen
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Liang Sheng
- School of Basic Medical Science, Nanjing Medical University, Nanjing, China
| | - Jiangyu Liang
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Feihua Wu
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
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19
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Dietary patterns and risk of non-alcoholic fatty liver disease in adults: A prospective cohort study. Clin Nutr 2021; 40:5373-5382. [PMID: 34560608 DOI: 10.1016/j.clnu.2021.08.021] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 02/18/2021] [Accepted: 08/25/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Prospective cohort studies linking dietary patterns and non-alcoholic fatty liver disease (NAFLD) are limited, especially in Asian populations. This study aimed to prospectively investigate the association between dietary patterns and risk of NAFLD in a general Chinese adult population. METHODS This study included a total of 17,360 participants free from NAFLD at baseline. Dietary patterns at baseline were identified with factor analysis based on responses to a validated 100-item food frequency questionnaire. NAFLD was diagnosed by abdominal ultrasound after excluding other causes related to chronic liver disease. Cox proportional regression models were used to assess the association between dietary patterns and risk of NAFLD. RESULTS During a median follow-up of 4.2 years, 4034 NAFLD cases were documented. Three main dietary patterns were extracted: sugar rich dietary pattern, vegetable rich dietary pattern, and animal food dietary pattern. After adjusting for age, sex, body mass index, smoking, alcohol, education, occupation, income, physical activity, total energy intake, personal and family history of disease, depressive symptoms, dietary supplement use, inflammation markers, and each other dietary pattern score, comparing the highest with the lowest quartiles of dietary pattern scores, the multivariable hazard ratios (95% confidence interval) of NAFLD were 1.11 (1.01, 1.23) for sugar rich dietary pattern, 0.96 (0.86, 1.07) for vegetable rich dietary pattern, and 1.22 (1.10, 1.36) for animal food dietary pattern. Further adjustment for waist circumference instead of body mass index provided similar results. CONCLUSION Dietary patterns rich in animal foods or sugar were associated with a higher risk of NAFLD among Chinese adults, whereas a vegetable rich dietary pattern was not associated.
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20
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Xia SJ, Tang LZ, Li WH, Xu ZS, Zhang LL, Cheng FG, Chen HX, Wang ZH, Luo YC, Dai AN, Fan JG. Serum syndecan-4 is associated with nonalcoholic fatty liver disease. J Dig Dis 2021; 22:536-544. [PMID: 34374198 DOI: 10.1111/1751-2980.13037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 07/08/2021] [Accepted: 08/06/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The accelerated shedding of extracellular domains of syndecan-4 (SDC4) is associated with central obesity and insulin resistance, while the association between serum SDC4 and nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to examine the association between SDC4 and NAFLD. METHODS Adults undergoing a health examination from 1 June 2019 to 31 December 2019 were enrolled. A diagnosis of NAFLD was made with an abdominal ultrasound. Logistic regression models and the receiver operating characteristic (ROC) curves were used to evaluate the role of SDC4 in predicting NAFLD. RESULTS In total, 533 eligible participants were finally enrolled, among them 157 (29.46%) had NAFLD. The proportion of patients with NAFLD increased with the increasing quartiles of serum SDC4. With the increase of serum SDC4 levels, metabolic features including waist circumference, serum triglyceride, total cholesterol, fasting blood glucose, fasting insulin and homeostasis model assessment of insulin resistance were significantly increased. SDC4 was an independent factor for NAFLD (odds ratio 1.963, 95% confidence interval [CI] 1.628-2.367, P < 0.001). The area under the ROC curve of SDC4 for predicting NAFLD was 0.934 (95% CI 0.910-0.959). The optimal cut-off value was 6.575 ng/mL at Youden's index of 0.767. SDC4 had the highest diagnostic sensitivity (84.1%), positive predictive value (82.5%), negative predictive value (93.3%) and positive likelihood ratio (11.356) among all the variables. CONCLUSIONS Elevated serum SDC4 level is associated with metabolic disorders and the prevalence of NAFLD among general population. Serum SDC4 may serve as a biomarker of NAFLD.
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Affiliation(s)
- Shu Jing Xia
- Department of Gastroenterology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu Province, China.,Department of Gastroenterology, Affiliated Xinghua People's Hospital of Yangzhou University Medical College, Xinghua, Jiangsu Province, China
| | - Li Zhong Tang
- Department of Pharmacy, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu Province, China
| | - Wen Hua Li
- Department of Gastroenterology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Zhao Shan Xu
- Department of Gastroenterology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu Province, China
| | - Li Li Zhang
- Department of Gastroenterology, Affiliated Xinghua People's Hospital of Yangzhou University Medical College, Xinghua, Jiangsu Province, China
| | - Feng Gan Cheng
- Department of Gastroenterology, Affiliated Xinghua People's Hospital of Yangzhou University Medical College, Xinghua, Jiangsu Province, China
| | - Hong Xia Chen
- Department of Gastroenterology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu Province, China
| | - Zi Hua Wang
- Department of Gastroenterology, Affiliated Xinghua People's Hospital of Yangzhou University Medical College, Xinghua, Jiangsu Province, China
| | - Yu Cheng Luo
- Department of Laboratory Medicine, Affiliated Xinghua People's Hospital of Yangzhou University Medical College, Xinghua, Jiangsu Province, China
| | - An Na Dai
- Department of Ultrasonography, Affiliated Xinghua People's Hospital of Yangzhou University Medical College, Xinghua, Jiangsu Province, China
| | - Jian Gao Fan
- Department of Gastroenterology, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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21
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Liu D, Wong CC, Zhou Y, Li C, Chen H, Ji F, Go MYY, Wang F, Su H, Wei H, Cai Z, Wong N, Wong VWS, Yu J. Squalene Epoxidase Induces Nonalcoholic Steatohepatitis Via Binding to Carbonic Anhydrase III and is a Therapeutic Target. Gastroenterology 2021; 160:2467-2482.e3. [PMID: 33647280 DOI: 10.1053/j.gastro.2021.02.051] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 02/19/2021] [Accepted: 02/22/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUNDS & AIMS Squalene epoxidase (SQLE) is the rate-limiting enzyme for cholesterol biosynthesis. We elucidated the functional significance, molecular mechanisms, and clinical impact of SQLE in nonalcoholic steatohepatitis (NASH). METHODS We performed studies with hepatocyte-specific Sqle overexpression transgenic (Sqle tg) mice and mice given high-fat high-cholesterol (HFHC) or methionine- and choline-deficient (MCD) diet to induce NASH. SQLE downstream target carbonic anhydrase III (CA3) was identified using co-immunoprecipitation and Western Blot. Some mice were given SQLE inhibitor (terbinafine) and CA3 inhibitor (acetazolamide) to study the therapeutic effects in NASH. Human samples (N = 217) including 65 steatoses, 80 NASH, and 72 healthy controls were analyzed for SQLE levels in liver tissue and in serum. RESULTS SQLE is highly up-regulated in human NASH and mouse models of NASH. Sqle tg mice triggered spontaneous insulin resistance, hepatic steatosis, liver injury, and accelerated HFHC or MCD diet-induced NASH development. Mechanistically, SQLE tg mice caused hepatic cholesterol accumulation, thereby triggering proinflammatory nuclear factor-κB signaling and steatohepatitis. SQLE directly bound to CA3, which induced sterol regulatory element-binding protein 1C activation, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase1 expression and de novo hepatic lipogenesis. Combined targeting SQLE (terbinafine) and CA3 (acetazolamide) synergistically ameliorated NASH in mice with superior efficacy to either drug alone. Serum SQLE with CA3 could distinguish patients with NASH from steatosis and healthy controls (area under the receiver operating characteristic curve, 0.815; 95% confidence interval, 0.758-0.871). CONCLUSIONS SQLE drives the initiation and progression of NASH through inducing cholesterol biosynthesis, and SQLE/CA3 axis-mediated lipogenesis. Combined targeting of SQLE and CA3 confers therapeutic benefit in NASH. Serum SQLE and CA3 are novel biomarkers for the noninvasive diagnosis of patients with NASH.
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Affiliation(s)
- Dabin Liu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Chi Chun Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Yunfei Zhou
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Chuangen Li
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Huarong Chen
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Fenfen Ji
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Minnie Y Y Go
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Feixue Wang
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Hao Su
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Hong Wei
- Department of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Zongwei Cai
- State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China
| | - Nathalie Wong
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
| | - Vincent W S Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
| | - Jun Yu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
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22
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Wang Q, Chang B, Li X, Zou Z. Role of ALDH2 in Hepatic Disorders: Gene Polymorphism and Disease Pathogenesis. J Clin Transl Hepatol 2021; 9:90-98. [PMID: 33604259 PMCID: PMC7868706 DOI: 10.14218/jcth.2020.00104] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 12/14/2020] [Accepted: 12/18/2020] [Indexed: 02/07/2023] Open
Abstract
Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme of alcohol metabolism and it is involved in the cellular mechanism of alcohol liver disease. ALDH2 gene mutations exist in about 8% of the world's population, with the incidence reaching 45% in East Asia. The mutations will result in impairment of enzyme activity and accumulation of acetaldehyde, facilitating the progression of other liver diseases, including non-alcoholic fatty liver diseases, viral hepatitis and hepatocellular carcinoma, through adduct formation and inflammatory responses. In this review, we seek to summarize recent research progress on the correlation between ALDH2 gene polymorphism and multiple liver diseases, with an attempt to provide clues for better understanding of the disease mechanism and for strategy making.
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Affiliation(s)
- Qiaoling Wang
- Peking University, 302 Clinical Medical School, Beijing, China
- Diagnosis and Treatment Center for Non-Infectious Liver Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Binxia Chang
- Diagnosis and Treatment Center for Non-Infectious Liver Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiaoyan Li
- Anhui Medical University, Hefei, Anhui, China
| | - Zhengsheng Zou
- Peking University, 302 Clinical Medical School, Beijing, China
- Diagnosis and Treatment Center for Non-Infectious Liver Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Correspondence to: Zhengsheng Zou, The Center for Diagnosis and Treatment of Non-Infectious Liver Disease, The General Hospital of Chinese People’s Liberation Army No. 5 Medical Science Center, No. 100 Xisihuan Middle Road, Beijing 100039, China. E-mail:
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23
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A Nomogram Model Based on Noninvasive Bioindicators to Predict 3-Year Risk of Nonalcoholic Fatty Liver in Nonobese Mainland Chinese: A Prospective Cohort Study. BIOMED RESEARCH INTERNATIONAL 2020; 2020:8852198. [PMID: 33204721 PMCID: PMC7655259 DOI: 10.1155/2020/8852198] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 10/08/2020] [Accepted: 10/25/2020] [Indexed: 12/13/2022]
Abstract
The purpose of this study is to establish and validate an accurate and personalized nonalcoholic fatty liver disease (NAFLD) prediction model based on the nonobese population in China. This study is a secondary analysis of a prospective study. We included 6,155 nonobese adults without NAFLD at baseline, with a median follow-up of 2.3 years. Univariate and multivariate Cox regression analyses were used to determine independent predictors. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize the selection of variables. Based on the results of multivariate analysis, a prediction model was established. Harrell's consistency index (C-index) and area under the curve (AUC) were used to determine the discrimination of the proposed model. The goodness of fit of the calibration model was tested, and the clinical application value of the model was evaluated by decision curve analysis (DCA). The participants were randomly divided into a training cohort (n = 4,605) and a validation cohort (n = 1,550). Finally, seven of the variables (HDL-c, BMI, GGT, ALT, TB, DBIL, and TG) were included in the prediction model. In the training cohort, the C-index and AUC value of this prediction model were 0.832 (95% confidence interval (CI), 0.820-0.844) and 0.861 (95% CI, 0.849-0.873), respectively. In the validation cohort, the C-index and AUC values of this prediction model were 0.829 (95% CI, 0.806-0.852) and 0.859 (95% CI, 0.841-0.877), respectively. The calibration plots demonstrated good agreement between the estimated probability and the actual observation. DCA demonstrated a clinically effective predictive model. Our nomogram can be used as a simple, reasonable, economical, and widely used tool to predict the 3-year risk of NAFLD in nonobese populations in China, which is helpful for timely intervention and reducing the incidence of NAFLD.
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24
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Zhang J, Ren Y, Bi J, Wang M, Zhang L, Wang T, Wei S, Mou X, Lv Y, Wu R. Involvement of kindlin-2 in irisin's protection against ischaemia reperfusion-induced liver injury in high-fat diet-fed mice. J Cell Mol Med 2020; 24:13081-13092. [PMID: 32954626 PMCID: PMC7701503 DOI: 10.1111/jcmm.15910] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 08/26/2020] [Accepted: 09/03/2020] [Indexed: 12/23/2022] Open
Abstract
Liver steatosis is associated with increased ischaemia reperfusion (I/R) injury. Our previous studies have shown that irisin, an exercise-induced hormone, mitigates I/R injury via binding to αVβ5 integrin. However, the effect of irisin on I/R injury in steatotic liver remains unknown. Kindlin-2 directly interacts with β integrin. We therefore suggest that irisin protects against I/R injury in steatotic liver via a kindlin-2 dependent mechanism. To study this, hepatic steatosis was induced in male adult mice by feeding them with a 60% high-fat diet (HFD). At 12 weeks after HFD feeding, the mice were subjected to liver ischaemia by occluding partial (70%) hepatic arterial/portal venous blood for 60 minutes, which was followed by 24 hours reperfusion. Our results showed HFD exaggerated I/R-induced liver injury. Irisin (250 μg/kg) administration at the beginning of reperfusion attenuated liver injury, improved mitochondrial function, and reduced oxidative and endoplasmic reticulum stress in HFD-fed mice. However, kindlin-2 inhibition by RNAi eliminated irisin's direct effects on cultured hepatocytes. In conclusion, irisin attenuates I/R injury in steatotic liver via a kindlin-2 dependent mechanism.
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Affiliation(s)
- Jia Zhang
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative MedicineShaanxi Provincial Center for Regenerative Medicine and Surgical EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
- Department of Hepatobiliary SurgeryFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
| | - Yifan Ren
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative MedicineShaanxi Provincial Center for Regenerative Medicine and Surgical EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
- Department of Hepatobiliary SurgeryFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
| | - Jianbin Bi
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative MedicineShaanxi Provincial Center for Regenerative Medicine and Surgical EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
- Department of Hepatobiliary SurgeryFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
| | - Mengzhou Wang
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative MedicineShaanxi Provincial Center for Regenerative Medicine and Surgical EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
- Department of Hepatobiliary SurgeryFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
| | - Lin Zhang
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative MedicineShaanxi Provincial Center for Regenerative Medicine and Surgical EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
- Department of Hepatobiliary SurgeryFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
| | - Tao Wang
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative MedicineShaanxi Provincial Center for Regenerative Medicine and Surgical EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
- Department of Hepatobiliary SurgeryFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
| | - Shasha Wei
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative MedicineShaanxi Provincial Center for Regenerative Medicine and Surgical EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
| | - Xingyi Mou
- Zonglian CollegeXi’an Jiaotong University Health Science CenterXi’anChina
| | - Yi Lv
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative MedicineShaanxi Provincial Center for Regenerative Medicine and Surgical EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
- Department of Hepatobiliary SurgeryFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
| | - Rongqian Wu
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative MedicineShaanxi Provincial Center for Regenerative Medicine and Surgical EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
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Helicobacter pylori infection may increase the severity of nonalcoholic fatty liver disease via promoting liver function damage, glycometabolism, lipid metabolism, inflammatory reaction and metabolic syndrome. Eur J Gastroenterol Hepatol 2020; 32:857-866. [PMID: 31714387 PMCID: PMC7269023 DOI: 10.1097/meg.0000000000001601] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Recent clinical trials have confirmed that Helicobacter pylori infection is positively associated with nonalcoholic fatty liver disease (NAFLD), although some research has shown a negative association. Therefore, to confirm whether H. pylori eradication treatment is feasible for NAFLD patients in our hospital, we aimed to establish the association between H. pylori infection and NAFLD. METHODS We enrolled 91 patients with NAFLD diagnosed by abdominal B-mode ultrasonography between January and December 2018. H. pylori infection was confirmed by C urea breath test, and liver function, glycometabolism, insulin sensitivity, lipid metabolism, as well as inflammatory reaction were assessed through blood biochemical analyses. RESULTS A minority of NAFLD patients had liver dysfunction, increased fasting glucose and insulin levels, a score of insulin-resistance (HOMA-Ir), lipid metabolism, slight inflammatory response, fasting hyperglycemia and hypertension. Most patients were complicated with overweight/visceral obesity and dyslipidemia. Moreover, these abnormal indicators were closely associated with the severity of NAFLD and H. pylori infection. Notably, the prevalence of H. pylori infection showed a significant difference between mild, moderate and severe NAFLD, and hepatic steatosis with coexistent NAFLD also revealed a striking difference between H. pylori-positive and H. pylori-negative patients (P < 0.01). CONCLUSION Our results suggest that H. pylori infection may be an independent risk factor in NAFLD progress.
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Xin FZ, Zhao ZH, Zhang RN, Pan Q, Gong ZZ, Sun C, Fan JG. Folic acid attenuates high-fat diet-induced steatohepatitis via deacetylase SIRT1-dependent restoration of PPARα. World J Gastroenterol 2020; 26:2203-2220. [PMID: 32476787 PMCID: PMC7235203 DOI: 10.3748/wjg.v26.i18.2203] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/27/2020] [Accepted: 04/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Folic acid has been shown to improve non-alcoholic steatohepatitis (NASH), but its roles in hepatic lipid metabolism, hepatic one-carbon metabolism, and gut microbiota are still unknown.
AIM To demonstrate the role of folic acid in lipid metabolism and gut microbiota in NASH.
METHODS Twenty-four Sprague-Dawley rats were assigned into three groups: Chow diet, high-fat diet (HFD), and HFD with folic acid administration. At the end of 16 wk, the liver histology, the expression of hepatic genes related to lipid metabolism, one-carbon metabolism, and gut microbiota structure analysis of fecal samples based on 16S rRNA sequencing were measured to evaluate the effect of folic acid. Palmitic acid-exposed Huh7 cell line was used to evaluate the role of folic acid in hepatic lipid metabolism.
RESULTS Folic acid treatment attenuated steatosis, lobular inflammation, and hepatocellular ballooning in rats with HFD-induced steatohepatitis. Genes related to lipid de novo lipogenesis, β-oxidation, and lipid uptake were improved in HFD-fed folic acid-treated rats. Furthermore, peroxisome proliferator-activated receptor alpha (PPARα) and silence information regulation factor 1 (SIRT1) were restored by folic acid in HFD-fed rats and palmitic acid-exposed Huh7 cell line. The restoration of PPARα by folic acid was blocked after transfection with SIRT1 siRNA in the Huh7 cell line. Additionally, folic acid administration ameliorated depleted hepatic one-carbon metabolism and restored the diversity of the gut microbiota in rats with HFD-induced steatohepatitis.
CONCLUSION Folic acid improves hepatic lipid metabolism by upregulating PPARα levels via a SIRT1-dependent mechanism and restores hepatic one-carbon metabolism and diversity of gut microbiota, thereby attenuating HFD-induced NASH in rats.
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Affiliation(s)
- Feng-Zhi Xin
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Ze-Hua Zhao
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Rui-Nan Zhang
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Qin Pan
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Zi-Zhen Gong
- Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
- Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
- Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Chao Sun
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
- Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
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Wang W, Wang C, Xu H, Gao Y. Aldehyde Dehydrogenase, Liver Disease and Cancer. Int J Biol Sci 2020; 16:921-934. [PMID: 32140062 PMCID: PMC7053332 DOI: 10.7150/ijbs.42300] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 01/03/2020] [Indexed: 12/19/2022] Open
Abstract
Acetaldehyde dehydrogenase 2 (ALDH2) is the key enzyme responsible for metabolism of the alcohol metabolite acetaldehyde in the liver. In addition to conversion of the acetaldehyde molecule, ALDH is also involved in other cellular functions. Recently, many studies have investigated the involvement of ALDH expression in viral hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and liver cancer. Notably, ALDH2 expression has been linked with liver cancer risk, as well as pathogenesis and prognosis, and has emerged as a promising therapeutic target. Of note, approximately 8% of the world's population, and approximately 30-40% of the population in East Asia carry an inactive ALDH2 gene. This review summarizes new progress in understanding tissue-specific acetaldehyde metabolism by ALDH2 as well as the association of ALDH2 gene polymorphisms with liver disease and cancer. New research directions emerging in the field are also briefly discussed.
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Affiliation(s)
- Wenjun Wang
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, 130021, China
| | - Chunguang Wang
- Department of Thoracic & Cardiovascular Surgery, Second Clinical College, Jilin University, Changchun, 130041, China
| | - Hongxin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, 130021, China
| | - Yanhang Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, 130021, China
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic diseases like type 2 diabetes and obesity. In recent decades, accumulating evidence has revealed that the hepatokines, proteins mainly secreted by the liver, play important roles in the development of NAFLD by acting directly on the lipid and glucose metabolism. As a member of organokines, the hepatokines establish the communication between the liver and the adipose, muscular tissues. In this review, we summarize the current understanding of the hepatokines and how they modulate the pathogenesis of metabolic disorders especially NAFLD.
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