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Soni J, Pathak N, Gharia M, Aswal D, Parikh J, Sharma P, Mishra A, Lalan D, Maheshwari T. Effectiveness of RESET care program: A real-world-evidence on managing non-alcoholic fatty liver disease through digital health interventions. World J Hepatol 2025; 17:101630. [PMID: 39871911 PMCID: PMC11736475 DOI: 10.4254/wjh.v17.i1.101630] [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: 09/23/2024] [Revised: 11/11/2024] [Accepted: 12/02/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) management requires sustainable lifestyle modifications. This study aimed to evaluate the effectiveness of the RESET care plan, a comprehensive program that is an integrated personalized diet, exercise, and cognitive behavior therapy, delivered via MyTatva's digital health application enabled through a body composition analyzer (BCA) and smartwatch. AIM To evaluates the effectiveness of the comprehensive program delivered via MyTatva's digital health app enabled through internet of thing devices. METHODS This retrospective observational study analyzed deidentified data from 22 participants enrolled in the MyTatva RESET care program. Participants were divided into three groups: Group A, diet plan; Group B, diet + exercise plan; and Group C, diet + exercise + cognitive behavioral therapy plan. Participants were provided with a BCA and smartwatch for continuous monitoring of anthropometric parameters. Statistical analysis, including one-way ANOVA and post-hoc Tukey's Honest Significant Difference test, was conducted to compare mean changes in anthropometric parameters across the groups. RESULTS All intervention groups showed significant improvement across all anthropometric parameters. Group C showed the most significant improvements, with mean weight reduction of 7% or more (6.99 ± 2.98 kg, 7.00% ± 3.39%; P = 0.002) from baseline, a benchmark associated with improved NAFLD conditions. Post-hoc analysis revealed that Group C had significantly greater improvements than Groups A and B. Weight reduction was observed in 85.7% of Group A participants, 77.8% of Group B participants, and 100% of Group C participants. CONCLUSION The comprehensive RESET care plan achieved a 7% weight reduction in 12 weeks, demonstrating its effectiveness in managing NAFLD. These results support adopting digitally supported, patient-centric approaches for NAFLD treatment.
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Affiliation(s)
- Jayesh Soni
- Department of Gastroenterology, Digestive Disease Clinic, Mumbai 400092, Mahārāshtra, India
| | - Nikhilesh Pathak
- Department of Endocrinology, DPC Health and Diabetic Clinic, Delhi 110008, India
| | - Mihir Gharia
- Medical Affairs, Tatvacare, Ahmedabad 380058, Gujarāt, India.
| | - Devina Aswal
- Medical Affairs, Tatvacare, Ahmedabad 380058, Gujarāt, India
| | - Jaymin Parikh
- Medical Affairs, Tatvacare, Ahmedabad 380058, Gujarāt, India
| | - Prachi Sharma
- Medical Affairs, Tatvacare, Ahmedabad 380058, Gujarāt, India
| | - Astha Mishra
- Medical Affairs, Tatvacare, Ahmedabad 380058, Gujarāt, India
| | - Dhvni Lalan
- Medical Affairs, Tatvacare, Ahmedabad 380058, Gujarāt, India
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Svobodová G, Horní M, Velecká E, Boušová I. Metabolic dysfunction-associated steatotic liver disease-induced changes in the antioxidant system: a review. Arch Toxicol 2025; 99:1-22. [PMID: 39443317 PMCID: PMC11748479 DOI: 10.1007/s00204-024-03889-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 10/09/2024] [Indexed: 10/25/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition characterized by liver steatosis, inflammation, consequent fibrosis, and cirrhosis. Chronic impairment of lipid metabolism is closely related to oxidative stress, leading to cellular lipotoxicity, mitochondrial dysfunction, and endoplasmic reticulum stress. The detrimental effect of oxidative stress is usually accompanied by changes in antioxidant defense mechanisms, with the alterations in antioxidant enzymes expression/activities during MASLD development and progression reported in many clinical and experimental studies. This review will provide a comprehensive overview of the present research on MASLD-induced changes in the catalytic activity and expression of the main antioxidant enzymes (superoxide dismutases, catalase, glutathione peroxidases, glutathione S-transferases, glutathione reductase, NAD(P)H:quinone oxidoreductase) and in the level of non-enzymatic antioxidant glutathione. Furthermore, an overview of the therapeutic effects of vitamin E on antioxidant enzymes during the progression of MASLD will be presented. Generally, at the beginning of MASLD development, the expression/activity of antioxidant enzymes usually increases to protect organisms against the increased production of reactive oxygen species. However, in advanced stage of MASLD, the expression/activity of several antioxidants generally decreases due to damage to hepatic and extrahepatic cells, which further exacerbates the damage. Although the results obtained in patients, in various experimental animal or cell models have been inconsistent, taken together the importance of antioxidant enzymes in MASLD development and progression has been clearly shown.
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Affiliation(s)
- Gabriela Svobodová
- Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05, Hradec Králové, Czech Republic
| | - Martin Horní
- Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05, Hradec Králové, Czech Republic
| | - Eva Velecká
- Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05, Hradec Králové, Czech Republic
| | - Iva Boušová
- Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05, Hradec Králové, Czech Republic.
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Tripathi M, Gauthier K, Sandireddy R, Zhou J, Guptta P, Sakthivel S, Teo WW, Naing YT, Arul K, Tikno K, Park SH, Wu Y, Wang L, Bay BH, Sun L, Giguere V, Chow PKH, Ghosh S, McDonnell DP, Yen PM, Singh BK. Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in metabolic dysfunction-associated steatohepatitis and reversed by alternate day fasting. Mol Metab 2024; 87:101997. [PMID: 39032642 PMCID: PMC11327444 DOI: 10.1016/j.molmet.2024.101997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 07/03/2024] [Accepted: 07/17/2024] [Indexed: 07/23/2024] Open
Abstract
OBJECTIVE Currently, little is known about the mechanism(s) regulating global and specific protein translation during metabolic dysfunction-associated steatohepatitis (MASH; previously known as non-alcoholic steatohepatitis, NASH). METHODS Unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling were used to understand protein translation activity in vitro and in vivo. RESULTS We observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of MASH. Interestingly, proteomic analysis showed that Rplp1, which regulates ribosome and translation pathways, was one of the most downregulated proteins. Moreover, decreased Esrra expression and binding to the Rplp1 promoter, diminished Rplp1 gene expression during lipotoxicity. This, in turn, reduced global protein translation and Esrra/Rplp1-dependent translation of lysosome (Lamp2, Ctsd) and autophagy (sqstm1, Map1lc3b) proteins. Of note, Esrra did not increase its binding to these gene promoters or their gene transcription, confirming its regulation of their translation during lipotoxicity. Notably, hepatic Esrra-Rplp1-dependent translation of lysosomal and autophagy proteins also was impaired in MASH patients and liver-specific Esrra knockout mice. Remarkably, alternate day fasting induced Esrra-Rplp1-dependent expression of lysosomal proteins, restored autophagy, and reduced lipotoxicity, inflammation, and fibrosis in hepatic cell culture and in vivo models of MASH. CONCLUSIONS Esrra regulation of Rplp1-mediated translation of lysosome/autolysosome proteins was downregulated during MASH. Alternate day fasting activated this novel pathway and improved MASH, suggesting that Esrra and Rplp1 may serve as therapeutic targets for MASH. Our findings also provided the first example of a nuclear hormone receptor, Esrra, to not only regulate transcription but also protein translation, via induction of Rplp1.
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Affiliation(s)
- Madhulika Tripathi
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Karine Gauthier
- Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie 69364 Lyon Cedex 07, France
| | - Reddemma Sandireddy
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Jin Zhou
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Priyanka Guptta
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Suganya Sakthivel
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Wei Wen Teo
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Yadanar Than Naing
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Kabilesh Arul
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Keziah Tikno
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Sung-Hee Park
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, C238A Levine Science Research Center, Durham, NC 27710, USA
| | - Yajun Wu
- Department of Anatomy, Yong Loo Lin School of Medicine, NUS 117594, Singapore
| | - Lijin Wang
- Centre for Computational Biology, Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore; Pennington Biomedical Research Center, Laboratory of Bioinformatics and Computational Biology, Baton Rouge, LA 70808, USA
| | - Boon-Huat Bay
- Department of Anatomy, Yong Loo Lin School of Medicine, NUS 117594, Singapore
| | - Lei Sun
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Vincent Giguere
- Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, Québec H3A 1A3, Canada
| | - Pierce K H Chow
- Dept of Surgery, Singapore General Hospital and Dept. of Surgical Oncology, National Cancer Centre 169608, Singapore
| | - Sujoy Ghosh
- Centre for Computational Biology, Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore; Pennington Biomedical Research Center, Laboratory of Bioinformatics and Computational Biology, Baton Rouge, LA 70808, USA
| | - Donald P McDonnell
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, C238A Levine Science Research Center, Durham, NC 27710, USA
| | - Paul M Yen
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore; Duke Molecular Physiology Institute and Dept. of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
| | - Brijesh K Singh
- Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (NUS) Medical School, Singapore 169857, Singapore.
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Zhang S, Cui Z, Zhang H, Wang P, Wang F, Zhang J. Pea Albumin Extracted from Pea ( Pisum sativum L.) Seeds Ameliorates High-Fat-Diet-Induced Non-Alcoholic Fatty Liver Disease by Regulating Lipogenesis and Lipolysis Pathways. Nutrients 2024; 16:2232. [PMID: 39064674 PMCID: PMC11280122 DOI: 10.3390/nu16142232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 07/07/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent liver disease globally. Pea albumin (PA) has demonstrated positive impacts on reducing obesity and improving glucose metabolism. In this research, a mouse model of NAFLD induced by a high-fat diet (HFD) was employed to examine the impact of PA on NAFLD and explore its potential mechanisms. The findings revealed that mice subjected to a HFD developed pronounced fatty liver alterations. The intervention with PA significantly lowered serum TC by 26.81%, TG by 43.55%, and LDL-C by 57.79%. It also elevated HDL-C levels by 1.2 fold and reduced serum ALT by 37.94% and AST by 31.21% in mice fed a HFD. These changes contributed to the reduction in hepatic steatosis and lipid accumulation. Additionally, PA improved insulin resistance and inhibited hepatic oxidative stress and inflammatory responses. Mechanistic studies revealed that PA alleviated lipid accumulation in HFD-induced NAFLD by activating the phosphorylation of AMPKα and ACC, inhibiting the expression of SREBF1 and FASN to reduce hepatic lipogenesis, and increasing the expression of ATGL, PPARα, and PPARγ to promote lipolysis and fatty acid oxidation. These results indicate that PA could serve as a dietary supplement for alleviating NAFLD, offering a theoretical foundation for the rational intake of PA in NAFLD intervention.
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Affiliation(s)
- Shucheng Zhang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (S.Z.); (H.Z.)
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China;
| | - Zhengwu Cui
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China;
| | - Hao Zhang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (S.Z.); (H.Z.)
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China;
| | - Pengjie Wang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (S.Z.); (H.Z.)
| | - Fuqing Wang
- Tibet Tianhong Science and Technology Co., Ltd., Lhasa 850000, China;
| | - Jian Zhang
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China;
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Su X, Xu Q, Li Z, Ren Y, Jiao Q, Wang L, Wang Y. Role of the angiopoietin-like protein family in the progression of NAFLD. Heliyon 2024; 10:e27739. [PMID: 38560164 PMCID: PMC10980950 DOI: 10.1016/j.heliyon.2024.e27739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 04/04/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease, with a range of conditions including non-alcoholic fatty liver, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Currently recognized as the liver component of the metabolic syndrome, NAFLD is intimately linked to metabolic diseases. Angiopoietin-like proteins (ANGPTLs) comprise a class of proteins that resemble angiopoietins structurally. It is closely related to obesity, insulin resistance and lipid metabolism, and may be the critical factor of metabolic syndrome. In recent years, many studies have found that there is a certain correlation between ANGPTLs and the occurrence and progression of NAFLD disease spectrum. This article reviews the possible mechanisms and roles of ANGPTL protein in the pathogenesis and progression of NAFLD.
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Affiliation(s)
- Xin Su
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, China
| | - Qinchen Xu
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, China
| | - Zigan Li
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, China
| | - Yidan Ren
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong Province, China
| | - Qinlian Jiao
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong Province, China
| | - Lina Wang
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, China
| | - Yunshan Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021, Jinan, Shandong Province, China
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Xu Y, Wang Y, Zhao Q, Chen B, Wang N, Zhang T, Jiang Y, Wu Y, He N, Zhao G, Liu X. Dairy products intake and prevalence, incidence, and recovery of non-alcoholic fatty liver disease in Chinese population. Hepatol Int 2024; 18:529-539. [PMID: 38409495 DOI: 10.1007/s12072-024-10638-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 01/03/2024] [Indexed: 02/28/2024]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a growing public health concern. Modifiable factors such as diet and lifestyle are of research interest in preventing or reversing the disease. The relationship between dairy products and NAFLD remains unclear. METHODS In this cohort study, 36,122 participants aged 20-74 were enrolled by multi-stage, stratified, randomized cluster sampling from 2016 to 2017. A total of 25,085 participants finished at least one follow-up visit from 2019 to 2023. Dairy intake was collected by food frequency questionnaire at baseline. NAFLD was defined as fatty liver diagnosed by ultrasonography with excessive alcohol drink excluded. Logistic regression and Cox proportional hazard models were used to analyze the association between dairy intake and NAFLD. RESULTS A total of 34,040 participants were included in the baseline analysis. The prevalence of NAFLD was inversely associated with dairy intake (OR>7vs 0 servings/week = 0.91, 95% CI 0.84-0.98; ORper serving/day increase = 0.95, 95% CI 0.92-0.99). 20,460 participants entered the follow-up analysis. Among 12,204 without NAFLD at baseline, 4,470 developed NAFLD after a median time of 4.3 years. The incidence of NAFLD was inversely associated with dairy intake (HR>7 vs 0 servings/week = 0.89, 95% CI 0.81-0.98; HRper serving/day increase = 0.94, 95% CI 0.89-0.99). Among 8256 with NAFLD at baseline, 3,885 recovered after 4.2-year follow-up. Total dairy intake did not show significant associations with recovery of NAFLD, and the HRs (95% CI) were 0.96 (0.87-1.06) for > 7 servings/week and 0.98 (0.93-1.03) for per serving/day increase. CONCLUSION Dairy product intake of more than one serving per day was associated with a lower prevalence and incidence of NAFLD in Chinese population. However, total dairy intake did not show significant association in NAFLD reversal.
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Affiliation(s)
- Yurou Xu
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Youyi Wang
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Qi Zhao
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Bo Chen
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Na Wang
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Tiejun Zhang
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Yonggen Jiang
- Songjiang District Center for Disease Control and Prevention, Shanghai, 201600, China
| | - Yiling Wu
- Songjiang District Center for Disease Control and Prevention, Shanghai, 201600, China
| | - Na He
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Genming Zhao
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Xing Liu
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China.
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Drapkina OM, Martynov AI, Arutyunov GP, Bakulin IG, Livzan MA, Maev IV, Egorov IV. Resolution of the Expert Forum "New therapeutic horizons of NAFLD". TERAPEVT ARKH 2024; 96:186-193. [DOI: 10.26442/00403660.2024.02.202648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Aim. To present the materials of the Expert Forum "New therapeutic horizons of NAFLD," held on December 19, 2023, on the updated nomenclature of fatty liver disease (FLD), its main issues of diagnosis and treatment, the burden of cardiovascular risk in FLD patients. Executive Summary of the Resolution. It is recommended that the latest update of the FLD nomenclature be considered for adaptation to the clinical practice of doctors of all therapeutic specialties. Due to the high prevalence of a combination of non-alcoholic fatty liver disease (NAFLD) and an alcoholic component in the Russian Federation, it is essential to distinguish this subgroup of patients. Numerous clinical conditions associated with NAFLD include cardiovascular disease, pre-diabetes/type 2 diabetes mellitus, polycystic ovary syndrome, obstructive sleep apnea, sarcopenic obesity, cholelithiasis, and chronic kidney disease. Once a diagnosis of NAFLD has been made, further examination of patients should be aimed at detecting the presence of fibrosis using non-invasive methods such as transient liver elastography, FibroTest, and calculation of the FIB-4 fibrosis index. The original ademethionine can be considered a universal drug in treating NAFLD due to reducing oxidative stress and correcting concomitant fatigue and asthenia.
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Bahari H, Rafiei H, Goudarzi K, Omidian K, Asbaghi O, Kolbadi KSH, Naderian M, Hosseini A. The effects of pomegranate consumption on liver function enzymes in adults: A systematic review and meta-analysis. Complement Ther Med 2024; 80:103008. [PMID: 38040096 DOI: 10.1016/j.ctim.2023.103008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 11/23/2023] [Accepted: 11/27/2023] [Indexed: 12/03/2023] Open
Abstract
BACKGROUND We performed a systematic review and meta-analysis of all published clinical trial studies to provide a more accurate estimation of pomegranate effects on liver enzymes in different clinical conditions. METHODS A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, and Scopus, up to March 2023 to identify eligible randomized clinical trials (RCTs) evaluating the effect of pomegranate consumption on liver function enzymes. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference with a 95% confidence interval. RESULTS Out of 3811 records, 9 eligible RCTs were included in the current study. However, there are limitations in the included studies, which can be mentioned in the dose, duration, and type of interventions that are different among the studies, as well as the small number of included studies. All this causes heterogeneity among studies and this heterogeneity limits the consistency of the results. Our meta-analysis showed that pomegranate intake had a significant effect on lowering aspartate aminotransferase (AST) levels in long-term intervention (> 8 weeks), obese (BMI≥30) individuals, or patients with metabolic disorders. Furthermore, results showed a significant decrease in alanine aminotransferase (ALT) levels in the long-term intervention (> 8 weeks) or in patients with metabolic disorders following the pomegranate intake. Combined results from the random-effects model indicated a significant reduction in gamma-glutamyl transferase (GGT) levels (WMD: -5.43 IU/L 95% CI: -7.78 to -3.08; p < 0.001;) following the pomegranate intake. The results of Egger's test mentioned a significant publication bias for the trials examining the effect of pomegranate intake on AST (p = 0.007) and ALT (p = 0.036). CONCLUSION Our results suggest that long-term pomegranate intake may be effective in ameliorating liver enzymes in adults with obesity and metabolic disorders who are more likely to have elevated baseline liver enzymes due to some degree of liver injury or tissue damage. However, some studies failed to conduct independent biochemical characterization of the product used, including the presence and quantity of polyphenols, antioxidants, and proanthocyanidins.
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Affiliation(s)
- Hossein Bahari
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Rafiei
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Kian Goudarzi
- Faculty of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Kosar Omidian
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Omid Asbaghi
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Moslem Naderian
- Department of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Ali Hosseini
- Department of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
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Shibayama K, Furushima C, Saka M, Sakamoto T, Takahashi H. Barriers to lifestyle modification in patients with non-alcoholic fatty liver disease: a scoping review. J Rural Med 2024; 19:1-9. [PMID: 38196808 PMCID: PMC10774003 DOI: 10.2185/jrm.2023-026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 08/03/2023] [Indexed: 01/11/2024] Open
Abstract
Objective: Non-alcoholic fatty liver disease is common worldwide, and lifestyle modifications are key to its treatment. This study aimed to identify the barriers to lifestyle modifications in patients with non-alcoholic fatty liver disease and to organize the results using the Capability Opportunity Motivation-Behavior (COM-B) model. Materials and Methods: The framework of Arksey and O' Malley was used in this scoping review. We searched PubMed, Scopus, and the Cochrane Library without language restrictions for reports published up to September 11, 2022, including peer-reviewed literature reporting barriers to lifestyle modifications in patients with non-alcoholic fatty liver disease. Patient-reported barriers were analyzed inductively and organized into the components (capability, opportunity, and motivation) of the COM-B model. Results: The literature search yielded 583 articles, of which seven qualitative studies, four quantitative studies, and one mixed-methods study met the inclusion criteria. Lack of time, lack of information on the diagnosis and management of non-alcoholic fatty liver disease, negative perceptions of the prescribed exercise and diet, physical symptoms interfering with the behavior, presence of comorbidities, and lack of family cooperation were frequently reported as barriers. Conclusion: The results of this study may contribute to the development of appropriate care and education strategies to promote behavioral changes in patients with non-alcoholic fatty liver disease.
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Affiliation(s)
- Kaoru Shibayama
- Institute of Nursing, Faculty of Medicine, Saga University, Japan
| | - Chie Furushima
- Institute of Nursing, Faculty of Medicine, Saga University, Japan
| | - Minako Saka
- Department of Nursing, School of Nursing at Narita, International University of Health and Welfare, Japan
| | - Takako Sakamoto
- Institute of Nursing, Faculty of Medicine, Saga University, Japan
| | - Hirokazu Takahashi
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Japan
- Liver Center, Saga University Hospital, Faculty of Medicine, Saga University, Japan
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Shi Y, Qi W. Histone Modifications in NAFLD: Mechanisms and Potential Therapy. Int J Mol Sci 2023; 24:14653. [PMID: 37834101 PMCID: PMC10572202 DOI: 10.3390/ijms241914653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/03/2023] [Accepted: 09/09/2023] [Indexed: 10/15/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a progressive condition that encompasses a spectrum of liver disorders, beginning with the simple steatosis, progressing to nonalcoholic steatohepatitis (NASH), and possibly leading to more severe diseases, including liver cirrhosis and hepatocellular carcinoma (HCC). In recent years, the prevalence of NAFLD has increased due to a shift towards energy-dense dietary patterns and a sedentary lifestyle. NAFLD is also strongly associated with metabolic disorders such as obesity and hyperlipidemia. The progression of NAFLD could be influenced by a variety of factors, such as diet, genetic factors, and even epigenetic factors. In contrast to genetic factors, epigenetic factors, including histone modifications, exhibit dynamic and reversible features. Therefore, the epigenetic regulation of the initiation and progression of NAFLD is one of the directions under intensive investigation in terms of pathogenic mechanisms and possible therapeutic interventions. This review aims to discuss the possible mechanisms and the crucial role of histone modifications in the framework of epigenetic regulation in NAFLD, which may provide potential therapeutic targets and a scientific basis for the treatment of NAFLD.
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Affiliation(s)
- Yulei Shi
- Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
| | - Wei Qi
- Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
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11
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Bottino R, Carbone A, Formisano T, D'Elia S, Orlandi M, Sperlongano S, Molinari D, Castaldo P, Palladino A, Barbareschi C, Tolone S, Docimo L, Cimmino G. Cardiovascular Effects of Weight Loss in Obese Patients with Diabetes: Is Bariatric Surgery the Additional Arrow in the Quiver? Life (Basel) 2023; 13:1552. [PMID: 37511927 PMCID: PMC10381712 DOI: 10.3390/life13071552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/01/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
Obesity is an increasingly widespread disease worldwide because of lifestyle changes. It is associated with an increased risk of cardiovascular disease, primarily type 2 diabetes mellitus, with an increase in major cardiovascular adverse events. Bariatric surgery has been shown to be able to reduce the incidence of obesity-related cardiovascular disease and thus overall mortality. This result has been shown to be the result of hormonal and metabolic effects induced by post-surgical anatomical changes, with important effects on multiple hormonal and molecular axes that make this treatment more effective than conservative therapy in determining a marked improvement in the patient's cardiovascular risk profile. This review, therefore, aimed to examine the surgical techniques currently available and how these might be responsible not only for weight loss but also for metabolic improvement and cardiovascular benefits in patients undergoing such procedures.
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Affiliation(s)
- Roberta Bottino
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
| | - Andreina Carbone
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
| | - Tiziana Formisano
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
| | - Saverio D'Elia
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
| | - Massimiliano Orlandi
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
| | - Simona Sperlongano
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Daniele Molinari
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
| | - Pasquale Castaldo
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
| | - Alberto Palladino
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
| | - Consiglia Barbareschi
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
| | - Salvatore Tolone
- Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, General, Mini-Invasive and Obesity Surgery Unit, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Ludovico Docimo
- Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, General, Mini-Invasive and Obesity Surgery Unit, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Giovanni Cimmino
- Cardiology Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Piazza Miraglia 2, 80138 Napoli, Italy
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
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12
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Musio A, Perazza F, Leoni L, Stefanini B, Dajti E, Menozzi R, Petroni ML, Colecchia A, Ravaioli F. Osteosarcopenia in NAFLD/MAFLD: An Underappreciated Clinical Problem in Chronic Liver Disease. Int J Mol Sci 2023; 24:ijms24087517. [PMID: 37108675 PMCID: PMC10139188 DOI: 10.3390/ijms24087517] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/07/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
Chronic liver disease (CLD), including non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), affects a significant portion of the population worldwide. NAFLD is characterised by fat accumulation in the liver, while NASH is associated with inflammation and liver damage. Osteosarcopenia, which combines muscle and bone mass loss, is an emerging clinical problem in chronic liver disease that is often underappreciated. The reductions in muscle and bone mass share several common pathophysiological pathways; insulin resistance and chronic systemic inflammation are the most crucial predisposing factors and are related to the presence and gravity of NAFLD and to the worsening of the outcome of liver disease. This article explores the relationship between osteosarcopenia and NAFLD/MAFLD, focusing on the diagnosis, prevention and treatment of this condition in patients with CLD.
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Affiliation(s)
- Alessandra Musio
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Federica Perazza
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Laura Leoni
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Division of Metabolic Diseases and Clinical Nutrition, Department of Specialistic Medicines, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy
| | - Bernardo Stefanini
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Elton Dajti
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Renata Menozzi
- Division of Metabolic Diseases and Clinical Nutrition, Department of Specialistic Medicines, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy
| | - Maria Letizia Petroni
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
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13
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Wang D, Ji DC, Yu CY, Wu DN, Qi L. Research progress on the mitochondrial mechanism of age-related non-alcoholic fatty liver. World J Gastroenterol 2023; 29:1982-1993. [PMID: 37155524 PMCID: PMC10122792 DOI: 10.3748/wjg.v29.i13.1982] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/20/2023] [Accepted: 03/13/2023] [Indexed: 04/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Reduced activity and slower metabolism in the elderly affect the balance of lipid metabolism in the liver leading to the accumulation of lipids. This affects the mitochondrial respiratory chain and the efficiency of β-oxidation and induces the overproduction of reactive oxygen species. In addition, the dynamic balance of the mitochondria is disrupted during the ageing process, which inhibits its phagocytic function and further aggravates liver injury, leading to a higher incidence of NAFLD in the elderly population. The present study reviewed the manifestations, role and mechanism of mitochondrial dysfunction in the progression of NAFLD in the elderly. Based on the understanding of mitochondrial dysfunction and abnormal lipid metabolism, this study discusses the treatment strategies and the potential therapeutic targets for NAFLD, including lipid accumulation, antioxidation, mitophagy and liver-protecting drugs. The purpose is to provide new ideas for the development of innovative drugs for the prevention and treatment of NAFLD.
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Affiliation(s)
- Dan Wang
- College of Basic Medicine, Beihua University, Jilin 132013, Jilin Province, China
| | - Duo-Chun Ji
- College of Basic Medicine, Beihua University, Jilin 132013, Jilin Province, China
| | - Chun-Yan Yu
- College of Basic Medicine, Beihua University, Jilin 132013, Jilin Province, China
| | - Dan-Ni Wu
- College of Basic Medicine, Beihua University, Jilin 132013, Jilin Province, China
| | - Ling Qi
- Central Laboratory, Qingyuan People's Hospital, Qingyuan 511518, Guangdong Province, China
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14
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Radlinger B, Ress C, Folie S, Salzmann K, Lechuga A, Weiss B, Salvenmoser W, Graber M, Hirsch J, Holfeld J, Kremser C, Moser P, Staudacher G, Jelenik T, Roden M, Tilg H, Kaser S. Empagliflozin protects mice against diet-induced obesity, insulin resistance and hepatic steatosis. Diabetologia 2023; 66:754-767. [PMID: 36525084 PMCID: PMC9947060 DOI: 10.1007/s00125-022-05851-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 10/31/2022] [Indexed: 12/23/2022]
Abstract
AIMS/HYPOTHESIS Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used in the treatment of type 2 diabetes, heart failure and chronic kidney disease. Their role in the prevention of diet-induced metabolic deteriorations, such as obesity, insulin resistance and fatty liver disease, has not been defined yet. In this study we set out to test whether empagliflozin prevents weight gain and metabolic dysfunction in a mouse model of diet-induced obesity and insulin resistance. METHODS C57Bl/6 mice were fed a western-type diet supplemented with empagliflozin (WDE) or without empagliflozin (WD) for 10 weeks. A standard control diet (CD) without or with empagliflozin (CDE) was used to control for diet-specific effects. Metabolic phenotyping included assessment of body weight, food and water intake, body composition, hepatic energy metabolism, skeletal muscle mitochondria and measurement of insulin sensitivity using hyperinsulinaemic-euglycaemic clamps. RESULTS Mice fed the WD were overweight, hyperglycaemic, hyperinsulinaemic and insulin resistant after 10 weeks. Supplementation of the WD with empagliflozin prevented these metabolic alterations. While water intake was significantly increased by empagliflozin supplementation, food intake was similar in WDE- and WD-fed mice. Adipose tissue depots measured by MRI were significantly smaller in WDE-fed mice than in WD-fed mice. Additionally, empagliflozin supplementation prevented significant steatosis found in WD-fed mice. Accordingly, hepatic insulin signalling was deteriorated in WD-fed mice but not in WDE-fed mice. Empagliflozin supplementation positively affected size and morphology of mitochondria in skeletal muscle in both CD- and WD-fed mice. CONCLUSIONS/INTERPRETATION Empagliflozin protects mice from diet-induced weight gain, insulin resistance and hepatic steatosis in a preventative setting and improves muscle mitochondrial morphology independent of the type of diet.
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Affiliation(s)
- Bernhard Radlinger
- Christian Doppler Laboratory for Metabolic Crosstalk, Medical University Innsbruck, Innsbruck, Austria
- Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
| | - Claudia Ress
- Christian Doppler Laboratory for Metabolic Crosstalk, Medical University Innsbruck, Innsbruck, Austria
- Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
| | - Sabrina Folie
- Christian Doppler Laboratory for Metabolic Crosstalk, Medical University Innsbruck, Innsbruck, Austria
- Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
| | - Karin Salzmann
- Christian Doppler Laboratory for Metabolic Crosstalk, Medical University Innsbruck, Innsbruck, Austria
- Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
| | - Ana Lechuga
- Christian Doppler Laboratory for Metabolic Crosstalk, Medical University Innsbruck, Innsbruck, Austria
- Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
| | - Bernhard Weiss
- Christian Doppler Laboratory for Metabolic Crosstalk, Medical University Innsbruck, Innsbruck, Austria
- Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
- Innpath GmbH, Innsbruck, Austria
| | - Willi Salvenmoser
- Institute of Zoology and Center of Molecular Biosciences Innsbruck (CBMI), Leopold Franzens University Innsbruck, Innsbruck, Austria
| | - Michael Graber
- Department of Cardiac Surgery, Medical University Innsbruck, Innsbruck, Austria
| | - Jakob Hirsch
- Department of Cardiac Surgery, Medical University Innsbruck, Innsbruck, Austria
| | - Johannes Holfeld
- Department of Cardiac Surgery, Medical University Innsbruck, Innsbruck, Austria
| | - Christian Kremser
- Department of Radiology, Medical University Innsbruck, Innsbruck, Austria
| | | | - Gabriele Staudacher
- Christian Doppler Laboratory for Metabolic Crosstalk, Medical University Innsbruck, Innsbruck, Austria
- Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
| | - Tomas Jelenik
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
| | - Herbert Tilg
- Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
| | - Susanne Kaser
- Christian Doppler Laboratory for Metabolic Crosstalk, Medical University Innsbruck, Innsbruck, Austria.
- Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria.
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15
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Lee J, Jo G, Park D, Jun HJ, Bae JH, Shin MJ. The Association between Advanced Liver Fibrosis and Mortality Is Modified by Dietary Quality among Korean Adults: Results from the Korea National Health and Nutrition Examination Survey with Mortality Data. Nutrients 2023; 15:nu15061501. [PMID: 36986234 PMCID: PMC10053070 DOI: 10.3390/nu15061501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/17/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023] Open
Abstract
Advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of mortality; however, an independent association of liver fibrosis with mortality is not well defined. We aimed to investigate the association between advanced liver fibrosis and all-cause and cardiovascular mortality and the mediation effect of diet quality. We analyzed 35,531 participants with suspected NAFLD, excluding competing etiologies of chronic liver disease, from the Korea National Health and Nutrition Examination Survey 2007-2015, and followed up until 31 December 2019. The severity of liver fibrosis was assessed using the NAFLD fibrosis score (NFS) and the fibrosis-4 index (FIB-4). The Cox proportional hazards model was used to examine the association of advanced liver fibrosis with mortality. During a mean 8.1 years of follow-up, 3426 deaths occurred. Advanced liver fibrosis determined by NFS and FIB-4 was associated with increased risks of all-cause and cardiovascular mortality after adjusting for confounders. When NFS and FIB-4 were combined, the high NFS + high FIB-4 group was significantly associated with higher risks of all-cause mortality (hazard ratio [HR] 1.85, 95% CI 1.42-2.43) and cardiovascular mortality (HR 2.04, 95% CI 1.23-3.39), respectively, compared with the low NFS + low FIB-4 group. However, these associations were attenuated in people with high diet quality. Advanced liver fibrosis is an independent risk factor for all-cause and cardiovascular mortality in people with NAFLD, and the association between advanced liver fibrosis and mortality is modified by a high-quality diet.
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Affiliation(s)
- Juhee Lee
- Interdisciplinary Program in Precision Public Health, Graduate School, Korea University, Seoul 02841, Republic of Korea
| | - Garam Jo
- Interdisciplinary Program in Precision Public Health, Graduate School, Korea University, Seoul 02841, Republic of Korea
| | - Dahyun Park
- Interdisciplinary Program in Precision Public Health, Graduate School, Korea University, Seoul 02841, Republic of Korea
| | - Hee Ju Jun
- Interdisciplinary Program in Precision Public Health, Graduate School, Korea University, Seoul 02841, Republic of Korea
| | - Jae Hyun Bae
- Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Min-Jeong Shin
- Interdisciplinary Program in Precision Public Health, Graduate School, Korea University, Seoul 02841, Republic of Korea
- School of Biosystems and Biomedical Sciences, College of Health Science, Korea University, Seoul 02841, Republic of Korea
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16
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Xu J, Wei Y, Huang Y, Wei X. Regulatory Effects and Molecular Mechanisms of Tea and Its Active Compounds on Nonalcoholic Fatty Liver Disease. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:3103-3124. [PMID: 36773311 DOI: 10.1021/acs.jafc.2c07702] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is a multifactorial disease resulting from the interaction between environment, genetic background, and metabolic stress. Most treatments for NAFLD include dietary intervention and exercise show limited efficacy due to the complex mechanisms involved in NAFLD. Meanwhile, drug therapy is accompanied by serious side effects. The development of high-efficiency natural supplements is a sustainable strategy for the prevention and treatment of NAFLD. As the second most consumed beverage, tea has health benefits that have been widely recognized. Nevertheless, the intervention of tea active compounds in NAFLD has received limited attention. Tea contains abundant bioactive compounds with potential effects on NAFLD, such as catechins, flavonoids, theanine, tea pigments, and tea polysaccharides. We reviewed the intrinsic and environmental factors and pathogenic mechanisms that affect the occurrence and development of NAFLD, and summarized the influences of exercise, drugs, diet, and tea drinking on NAFLD. On this basis, we further analyzed the potential effects and molecular regulatory mechanisms of tea active compounds on NAFLD and proposed future development directions. This review hopes to provide novel insights into the development and application of tea active compounds in the prevention and treatment of NAFLD.
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Affiliation(s)
- Jia Xu
- School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
- School of Environmental and Chemical Engineering, Shanghai University, 333 Nanchen Road, Shanghai 200240, PR China
| | - Yang Wei
- School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
| | - Yi Huang
- School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
| | - Xinlin Wei
- School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
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17
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Yang K, Kim HH, Shim YR, Song MJ. The Efficacy of Panax ginseng for the Treatment of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies. Nutrients 2023; 15:nu15030721. [PMID: 36771427 PMCID: PMC9919883 DOI: 10.3390/nu15030721] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 01/20/2023] [Accepted: 01/30/2023] [Indexed: 02/04/2023] Open
Abstract
Although tremendous research has reported the protective effects of natural compounds in nonalcoholic fatty liver disease (NAFLD), there is still no approved drug. This study aimed to examine the efficacy of Panax ginseng in NAFLD in preclinical studies. A total of 41 studies were identified by searching the PubMed, Web of Science, and Cochrane Library databases. The methodological quality was assessed by the risk of bias tool from the Systematic Review Center for Laboratory Animal Experimentation. The standardized mean difference (SMD) with a 95% confidence interval was calculated, and the random effects model was used to examine overall efficacy or heterogeneity. The publication bias was analyzed by Egger's test. The results showed that Panax ginseng treatment significantly reduced the systemic levels of alanine aminotransferase (SMD: -2.15 IU/L; p < 0.0001), aspartate aminotransferase (SMD: -2.86 IU/L; p < 0.0001), triglyceride (SMD: -2.86 mg/dL; p < 0.0001), total cholesterol (SMD: -1.69 mg/dL; p < 0.0001), low-density lipoprotein (SMD: -1.46 mg/dL; p < 0.0001), and fasting glucose (SMD: -1.45 mg/dL; p < 0.0001) while increasing high-density lipoprotein (SMD: 1.22 mg/dL; p = 0.0002) in NAFLD regardless of animal models or species. These findings may suggest that Panax ginseng is a promising therapeutic agent for NAFLD treatment.
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Affiliation(s)
- Keungmo Yang
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| | - Hee-Hoon Kim
- Life Science Research Institute, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
| | - Young-Ri Shim
- Life Science Research Institute, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
| | - Myeong Jun Song
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
- Correspondence:
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18
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Screening of Biomarkers in Liver Tissue after Bariatric Surgery Based on WGCNA and SVM-RFE Algorithms. DISEASE MARKERS 2023; 2023:2970429. [PMID: 36755803 PMCID: PMC9902125 DOI: 10.1155/2023/2970429] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 01/09/2023] [Accepted: 01/16/2023] [Indexed: 02/03/2023]
Abstract
As the most common chronic liver disease around the world, nonalcoholic fatty liver disease (NAFLD) has a close connection with obesity, diabetes, and metabolic syndrome. Bariatric surgery (BS) is considered to be the most effective treatment for NAFLD. However, the regulatory mechanism of hepatic lipid metabolism after BS remains poorly elucidated. By analyzing two transcriptome datasets regarding liver tissues after BS, namely, GSE83452 and GSE106737, we acquired 110 differentially expressed genes (DEGs). By further analysis of DEGs in terms of the weighted gene coexpression network analysis (WGCNA) and support vector machine-recursive feature elimination (SVM-RFE) algorithms, we identified four crucial genes participating in the regulation of hepatic lipid metabolism: SRGN, THEMIS2, SGK1, and FPR3. In addition, the results of gene set enrichment analysis (GSEA) showed that BS can activate immune-related regulatory pathways and change immune cell infiltration levels. Finally, through cellular level studies, we found that the silencing of SRGN affects the expression of SREBP-1, SIRT1, and FAS during adipogenesis in the liver and the formation of lipid droplets in the liver. In summary, the immune system in the liver is activated after BS, and SRGN participates in the regulation of hepatic lipid metabolism.
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19
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Musazadeh V, Karimi A, Malekahmadi M, Ahrabi SS, Dehghan P. Omega-3 polyunsaturated fatty acids in the treatment of non-alcoholic fatty liver disease: An umbrella systematic review and meta-analysis. Clin Exp Pharmacol Physiol 2023; 50:327-334. [PMID: 36692292 DOI: 10.1111/1440-1681.13750] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 12/17/2022] [Accepted: 01/10/2023] [Indexed: 01/25/2023]
Abstract
There has been conflicting evidence from meta-analyses on the effect of polyunsaturated fatty acids (PUFA) on non-alcoholic fatty liver disease (NAFLD). Therefore, in this umbrella meta-analysis, we are evaluating whether omega-3 PUFA supplementation has any benefit in treating NAFLD. Electronic databases such as PubMed, Web of Science, Scopus, Embase and Google Scholar were assessed to October 2022. This meta-analysis included all meta-analyses that examined the effect of PUFAs on liver fat and liver function tests [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)]. Meta-analysis was conducted using a random effects model. Subgroup analyses and sensitivity analyses were also performed. In total, eight articles involving 6,561 participants met the eligibility criteria. Advantageous impacts PUFA supplementation were observed on ALT (ESWMD = -6.72 IU/L; 95% CI: -8.61, -4.84; p < 0.001, and ESSMD = -0.52 IU/L; 95% CI: -0.84, -0.20, p < 0.001), AST (ESWMD = -3.73 IU/L, 95% CI: -5.93, -1.53, p < 0.001, and ESSMD = -0.65 IU/L; 95% CI: -1.08, -0.22, p = 0.003), GGT levels (ESWMD = -4.20 IU/L, 95% CI: -6.85, -1.55, p = 0.002), and liver fat (ESWMD = -5.16; 95% CI: -8.49, -1.82, p < 0.001). Intervention with omega-3 PUFAs improves ALT, AST, GGT, and liver fat in patients with NAFLD. Thus, omega-3 PUFAs could be considered as a therapeutic option in the treatment of NAFLD.
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Affiliation(s)
- Vali Musazadeh
- Student Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Arash Karimi
- Nutrition Research Center, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran.,Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahsa Malekahmadi
- Nutrition Department, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Sana Sedgh Ahrabi
- Student Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parvin Dehghan
- Nutrition Research Center, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
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Seifi N, Bahari H, Soltani S, Nikoumanesh M, Hajipoor M, Ferns GA, Ghayour-Mobarhan M. The effects of electronic-based lifestyle interventions on nonalcoholic fatty liver disease: A systematic review. Digit Health 2023; 9:20552076231187597. [PMID: 37529544 PMCID: PMC10388623 DOI: 10.1177/20552076231187597] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 06/23/2023] [Indexed: 08/03/2023] Open
Abstract
Objective Lifestyle interventions are increasingly becoming an integrated part of nonalcoholic fatty liver disease (NAFLD) management. Electronic lifestyle interventions may be able to expand the access and utility of this approach. This study aimed to synthesize the evidence for the effects of electronic-based lifestyle interventions on weight, anthropometric, and liver enzyme measurements in patients with NAFLD. Methods Medline, Scopus, and Web of Science were searched up to February 2023. Clinical trials investigating the effects of electronic lifestyle interventions on weight, body mass index (BMI), waist circumference (WC), and liver enzymes in NAFLD patients were reviewed. After reviewing full-text articles, seven clinical trials were included in the systematic review. Results Two articles included telephone calls, one was based on text messaging, two studies were based on web-based lifestyle modifications, and two used mobile apps. Except for one, all other six studies indicated a significant impact on weight loss. BMI was reported in six of seven studies. Except for one, BMI was significantly reduced in the group receiving e-health. WC was reported in four studies, which indicated a significant reduction in the e-health intervention group. Alanine transaminase (ALT) was reported in all the included studies. Except for two, others demonstrated a significant improvement in ALT in the e-health intervention groups. As reported in four studies, Aspartate transaminase (AST) significantly decreased in the group receiving e-health interventions, except in one study. Conclusions The results support applying electronic lifestyle interventions in NAFLD patients to reduce weight, BMI, WC, AST, and ALT.
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Affiliation(s)
- Najmeh Seifi
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Bahari
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sanaz Soltani
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahya Nikoumanesh
- Department of Nutrition Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
| | - Mojtaba Hajipoor
- Department of Nutrition Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
| | - Gordon A. Ferns
- Department of Medical Education, Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex, UK
| | - Majid Ghayour-Mobarhan
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
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Kong CY, Li ZM, Chen HL, Mao YQ, Han B, Guo JJ, Wang LS. An Energy-Restricted Diet Including Yogurt, Fruit, and Vegetables Alleviates High-Fat Diet-Induced Metabolic Syndrome in Mice by Modulating the Gut Microbiota. J Nutr 2022; 152:2429-2440. [PMID: 36774109 DOI: 10.1093/jn/nxac181] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 06/02/2022] [Accepted: 08/12/2022] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND The importance of the composition of an energy-restricted diet in the treatment of metabolic syndrome (MetS) is unknown. OBJECTIVES In this study we aimed to investigate the benefits of a novel dietary treatment (50% calorie restriction diet composed of yogurt, fruit, and vegetables [CR-YD]) in mice with MetS. METHODS Forty 7-wk-old male C57BL/6 J mice were randomly assigned to 4 groups (n = 10/group) that were fed for 14 wk ad libitum with a normal diet (ND; 10%:70%:20% energy from fat: carbohydrate: protein) or for 12 wk with a high-fat diet (HFD; 60:20:20) or the HFD followed by 2 wk of feeding with a 50% calorie-restricted HFD (CR-HFD) or YD (CR-YD, 21.2%:65.4%:13.4% energy). Body weight, fat deposition, hepatic steatosis, serum concentrations of inflammatory biomarkers, and glucose homeostasis were assessed. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in MetS. RESULTS The HFD group had 50% greater body weight and 475% greater fat deposition than the ND group (P < 0.05). Compared with the HFD group, the CR-HFD and CR-YD groups had 22% and 31% lower body weight and 49% and 75% less fat deposition, respectively (P < 0.05). Compared with the CR-HFD group, the CR-YD group had 11% lower body weight, 96% less fat deposition, 500% less hepatic steatosis, 75% lower glucose, and 450% more hepatic Akkermansia bacteria (P < 0.05). The CR-YD group also had 50% lower histopathology scores and 1.35-fold higher levels of Claudin4 than the CR-HFD group (P < 0.05). The HFD + CR-YD fecal group had 10.6% lower body weight, 119% lower steatosis, and 17.9% lower glucose (P < 0.05) than the HFD + CR-HFD fecal group. CONCLUSIONS Compared with CR alone, the CR-YD diet has a better therapeutic effect in mice with HFD-induced MetS.
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Affiliation(s)
- Chao-Yue Kong
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Zhan-Ming Li
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Hui-Ling Chen
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China
| | - Yu-Qin Mao
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Bing Han
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Jian-Jun Guo
- Sports and Medicine Integration Center, Capital University of Physical Education and Sports, Beijing, China.
| | - Li-Shun Wang
- Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.
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22
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Cuda SE, Kharofa R, Williams DR, O'Hara V, Conroy R, Karjoo S, Paisley J, Censani M, Browne NT. Metabolic, behavioral health, and disordered eating comorbidities associated with obesity in pediatric patients: An Obesity Medical Association (OMA) Clinical Practice Statement 2022. OBESITY PILLARS 2022; 3:100031. [PMID: 37990723 PMCID: PMC10662000 DOI: 10.1016/j.obpill.2022.100031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 08/01/2022] [Indexed: 11/23/2023]
Abstract
Background This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details metabolic, behavioral health, and disordered eating comorbidities associated with obesity in children. This CPS will be followed by a companion CPS covering further comorbidities, including genetics and social consequences related to overweight and obesity. These CPSs are intended to provide clinicians with an overview of clinical practices applicable to children and adolescents with body mass indices greater than or equal to the 95th percentile for their ages, particularly those with adverse consequences resulting from increased body mass. The information in this CPS is based on scientific evidence, supported by the medical literature, and derived from the clinical experiences of members of the OMA. Methods The scientific information and clinical guidance in this CPS is based upon referenced evidence and derived from the clinical perspectives of the authors. Results This OMA statement details metabolic, behavioral health, and disordered eating comorbidities associated with obesity in children. It provides clinical information regarding identifying and treating metabolic, behavioral health, and disordered eating comorbidities associated with obesity in children over the 95th percentile of weight/height for age. Conclusions This OMA clinical practice statement details metabolic, behavioral health, and disordered eating comorbidities associated with obesity in children and provides an overview of current recommendations. These recommendations lay out a roadmap to the improvement of the health of children and adolescents with obesity, especially those with metabolic, physiological, and psychological complications.
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Affiliation(s)
- Suzanne E. Cuda
- Alamo City Healthy Kids and Families, 1919 Oakwell Farms Parkway, Ste 145, San Antonio, TX, 78218, USA
| | - Roohi Kharofa
- Center for Better Health & Nutrition, The Heart Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA
| | - Dominique R. Williams
- The Ohio State University College of Medicine Center for Healthy Weight and Nutrition, Nationwide Children's Hospital, 700 Children's Drive LA, Suite 5F, Columbus, OH, 43215, USA
| | - Valerie O'Hara
- WOW 4 Wellness Clinic/ PCHC, 6 Telcom Drive, Bangor, ME, 04401, USA
| | - Rushika Conroy
- Division of Pediatric Endocrinology, Baystate Children's Hospital Subspecialty Center, 50 Wason Avenue, Springfield, MA, 01107, USA
| | - Sara Karjoo
- Johns Hopkins All Children's Hospital, Pediatric Gastroenterology, 501 6th Ave S St. Petersburg, FL, 33701, USA
| | - Jennifer Paisley
- St Elizabeth Physician's Group Primary Care, 98 Elm Street, Lawrenceburg, IN, 47025-2048, USA
| | - Marisa Censani
- Division of Pediatric Endocrinology, Department of Pediatrics, New York Presbyterian Hospital, Weill Cornell Medicine, 525 East 68th Street, Box 103, New York, NY, 10021, USA
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Li Y, Xu YJ, Tan CP, Liu Y. Sinapine improves LPS-induced oxidative stress in hepatocytes by down-regulating MCJ protein expression. Life Sci 2022; 306:120828. [PMID: 35872005 DOI: 10.1016/j.lfs.2022.120828] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 07/09/2022] [Accepted: 07/17/2022] [Indexed: 11/25/2022]
Abstract
Oxidative stress is an important part of the development of NAFLD, and hepatic injury can be prevented by inhibiting oxidative stress. In this study, we investigated the potential role of sinapine in protecting the liver. LPS was selected to establish the oxidative stress model of THLE-2 cells, and the treatment concentrations of LPS (5 μg/mL) and sinapine (5 μM, 20 μM, and 80 μM) were determined by toxicity experiments. The MDA of the sinapine (80 μM) pretreatment group was 1.09 ± 0.13 nmol/mg prot which was reduced by 27.67 % compared with the LPS group. Furthermore, SOD and GSH-Px levels were significantly increased by 40.61 % and 49.60 %, respectively. And the ROS levels of 20 and 80 μM sinapine were reduced by 31.47 % and 40.31 %, respectively (p < 0.01) compared with the model group. The mitochondrial membrane potential had similar results. It was also found that sinapine can significantly down-regulate the level of MCJ protein (p < 0.01), which is related to oxidative stress. Our results indicate that sinapine can maintain liver health by down-regulating the expression of MCJ protein to inhibit oxidative stress, which provides a theoretical basis for the use of sinapine as an inhibitor of MCJ.
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Affiliation(s)
- Youdong Li
- School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, People's Republic of China; College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, People's Republic of China
| | - Yong-Jiang Xu
- School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, People's Republic of China; State Key Laboratory of Food Science and Technology, National Engineering Laboratory for Cereal Fermentation Technology, National Engineering Research Center for Functional Food, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, People's Republic of China
| | - Chin Ping Tan
- Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Yuanfa Liu
- School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, People's Republic of China; State Key Laboratory of Food Science and Technology, National Engineering Laboratory for Cereal Fermentation Technology, National Engineering Research Center for Functional Food, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, People's Republic of China.
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24
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Zhang X, Li J, Liu T, Zhao M, Liang B, Chen H, Zhang Z. Identification of Key Biomarkers and Immune Infiltration in Liver Tissue after Bariatric Surgery. DISEASE MARKERS 2022; 2022:4369329. [PMID: 35789605 PMCID: PMC9250435 DOI: 10.1155/2022/4369329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/13/2022] [Accepted: 05/31/2022] [Indexed: 11/17/2022]
Abstract
Background Few drugs are clearly available for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH); nevertheless, mounting studies have provided sufficient evidence that bariatric surgery is efficient for multiple metabolic diseases, including NAFLD and NASH, while the molecular mechanisms are still poorly understood. Methods The mRNA expression profiling of GSE48452 and GSE83452 were retrieved and obtained from the Gene Expression Omnibus (GEO) database. The limma package was employed for identifying differentially expressed genes (DEGs), followed by clusterProfiler for performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and GSEA software for performing GSEA analyses. The PPI network analyses were constructed using Metascape online analyses. WGCNA was also utilized to identify and verify the hub genes. CIBERSORT tools contributed to the analysis of immune cell infiltration of liver diseases. Results We identify coexpressed differential genes including 10 upregulated and 55 downregulated genes in liver tissue after bariatric surgery. GO and KEGG enrichment analyses indicated that DEGs were remarkably involved in the immune response. GSEA demonstrated that DEGs were markedly enriched in the immune response before surgery, while most were enriched in metabolism after surgery. Seven genes were screened through the MCC algorithm and KME values, including SRGN, CD53, EVI2B, MPEG1, NCKAP1L, LCP1, and TYROBP. The mRNA levels of these genes were verified in the Attie Lab Diabetes Database, and only LCP1 was found to have significant differences and correlation with certain immune cells. Conclusion Our knowledge of the mechanisms by which bariatric surgery benefits the liver and the discovery of LCP1 is expected to serve as potential biomarkers or therapeutic targets for NAFLD and NASH.
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Affiliation(s)
- Xiaoyan Zhang
- Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Department of Pediatrics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Jingxin Li
- Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Tiancai Liu
- School of Laboratory Medicine and Biotechnology, Institute of Antibody Engineering, Southern Medical University, Guangzhou, China
| | - Min Zhao
- Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Baozhu Liang
- Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Hong Chen
- Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Zhen Zhang
- Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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25
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Musazadeh V, Roshanravan N, Dehghan P, Ahrabi SS. Effect of Probiotics on Liver Enzymes in Patients With Non-alcoholic Fatty Liver Disease: An Umbrella of Systematic Review and Meta-Analysis. Front Nutr 2022; 9:844242. [PMID: 35677540 PMCID: PMC9169800 DOI: 10.3389/fnut.2022.844242] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 05/02/2022] [Indexed: 12/20/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become prevalent in recent decades, especially in developed countries; yet the approaches for preventing and treating NAFLD are not clear. This study aimed to summarize meta-analyses of randomized controlled trials that examined the effects of probiotics on NAFLD. We systematically searched PubMed, Scopus, Embase, Web of Science, and Cochrane Central Library databases up to August 2021. All Meta-analysis studies assessing the effect of probiotics on liver function tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Gamma-glutamyl transferase (GGT)] were included. Meta-analysis was conducted using a random-effects model. Sensitivity and subgroup analyses were also performed. The umbrella study covered ten eligible studies involving 5,162 individuals. Beneficial effects of probiotics supplementation were revealed on ALT (ES = −10.54 IU/L; 95% CI: −12.70, −8.39; p < 0.001; I2 = 60.9%, p = 0.006), AST (ES = −10.19 IU/L, 95%CI: −13.08, −7.29, p < 0.001; I2 = 79.8%, p < 0.001), and GGT (ES = −5.88 IU/L, 95% CI: −7.09, −4.67, p = 0.009; I2 = 0.0%, p = 0.591) levels. Probiotics have ameliorating effects on ALT, AST, and GGT levels in patients with NAFLD. Overall, Probiotics could be recommended as an adjuvant therapeutic method for the management of NAFLD.
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Affiliation(s)
- Vali Musazadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Community Nutrition, School of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Roshanravan
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parvin Dehghan
- Faculty of Nutrition and Food Science, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- *Correspondence: Parvin Dehghan,
| | - Sana Sedgh Ahrabi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
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26
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Explore the Mechanism of Astragalus mongholicus Bunge against Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Experimental Verification. Gastroenterol Res Pract 2022; 2022:4745042. [PMID: 35422858 PMCID: PMC9005278 DOI: 10.1155/2022/4745042] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 03/08/2022] [Indexed: 02/06/2023] Open
Abstract
Objective Astragalus mongholicus Bunge [Fabaceae] (AMB), a traditional Chinese medicine (TCM), has been widely used to treat liver diseases in the clinic. However, the efficacy and mechanism of AMB in the treatment of nonalcoholic fatty liver disease (NAFLD) remain unclear. The purpose of this study was to systematically investigate the active components and mechanisms of AMB against NAFLD based on network pharmacology, molecular docking, and experimental verification. Methods First, the bioactive components and relevant targets of AMB were screened from the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database, and NAFLD-related targets were obtained from the GeneCards database. Then, the AMB-NAFLD protein target interaction network was built by the STRING database. GO and KEGG pathway enrichment analyses were performed using the DAVID database. The component targets were visualized using Cytoscape software. Finally, molecular docking and experiments were used to verify the results of network pharmacological prediction. Results Network pharmacology predicted that quercetin may be the main active component in AMB, and the TNF and MAPK signaling pathways may be the key targets of AMB against NAFLD. Molecular docking validation results demonstrated that quercetin, as the main active component of AMB, had the highest binding affinity with TNF. Furthermore, quercetin played a distinct role in alleviating NAFLD through in vitro experiments. Quercetin upregulated the phosphorylation levels of AMPK and inhibited the expression of p-MAPK and TNF-α. In addition, we further discovered that quercetin could increase ACC phosphorylation and CPT1α expression in PA-induced HepG2 cells. Conclusions Our results indicated that quercetin, as the main active component in AMB, exerts an anti-NAFLD effect by regulating the AMPK/MAPK/TNF-α and AMPK/ACC/CPT1α signaling pathways to inhibit inflammation and alleviate lipid accumulation.
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Fernández T, Viñuela M, Vidal C, Barrera F. Lifestyle changes in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis. PLoS One 2022; 17:e0263931. [PMID: 35176096 PMCID: PMC8853532 DOI: 10.1371/journal.pone.0263931] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 01/30/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease is a liver condition that is increasing worldwide and expected to become the number one cause of cirrhosis and hepatocellular carcinoma in the next 5 years. Currently there are no successful or approved pharmacological treatments. Weight loss is the first-line therapy as a 7 to 10% reduction improves steatosis, inflammation, hepatocyte ballooning, and fibrosis. To achieve this, lifestyle interventions including daily exercise and diet must be encouraged. We aimed to assess the effects of diet, exercise, or a combination of both compared to conventional treatment in patients with non-alcoholic fatty liver disease. METHODS AND FINDING A literature search was performed in CENTRAL, EMBASE, and PubMed. Randomized controlled trials comparing lifestyle changes with conventional treatment were included, without date restriction. Two authors searched studies according to eligibility criteria, extracted data, and assessed study quality. Subgroup analysis was made by type of intervention, duration of intervention and supervision. We calculated mean differences between the intervention and the control group with their corresponding 95% confidence intervals. Quality of the evidence was assessed using the Cochrane Risk of bias tool. This study is registered in PROSPERO, number CRD42020184241, and checked with the PRISMA checklist. 30 RCTs met the inclusion criteria. Compared to conventional treatment, combined exercise with diet seems to elicit greater reductions in ALT (MD: -13.27 CI 95% -21.39, -5.16), AST (MD: -7.02 CI 95% -11.26, -2.78) and HOMA-IR (MD: -2.07 CI 95% -2.61, -1.46) than diet (ALT MD: -4.48 CI 95% -1.01, -0.21; HOMA-IR MD: -0.61 CI 95% -1.01, -0.21) and exercise (ALT and AST non-significant; HOMA-IR MD = -0.46 CI 95% -0.8, -0.12) alone. Additionally, exercise improved quality of life, cardiorespiratory fitness, and weight (MD: -2.64 CI 95% -5.18, -0.09). CONCLUSION Lifestyle changes are effective in the treatment of NAFLD. Diet and exercise combined are superior to these interventions alone in improving liver enzymes and HOMA-IR.
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Affiliation(s)
- Tiziana Fernández
- Departamento Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Macarena Viñuela
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Catalina Vidal
- Departamento de Ortopedia y Traumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Barrera
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
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Tzanaki I, Agouridis AP, Kostapanos MS. Is there a role of lipid-lowering therapies in the management of fatty liver disease? World J Hepatol 2022; 14:119-139. [PMID: 35126843 PMCID: PMC8790403 DOI: 10.4254/wjh.v14.i1.119] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/30/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open
Abstract
Atherogenic dyslipidemia is characterized by increased triglyceride-rich lipoproteins and low high-density lipoprotein cholesterol concentrations. It is highly prevalent in non-alcoholic fatty liver disease (NAFLD) and contributes to the increased cardiovascular risk associated with this condition. Alongside insulin resistance it plays an important pathogenetic role in NAFLD/non-alcoholic steatohepatitis (NASH) development and progression. It has been shown that cholesterol-lowering reduces cardiovascular risk more in NAFLD vs non-NAFLD high-risk individuals. This evidence highlights the importance of effective lipid modulation in NAFLD. In this narrative review the effects of the most commonly used lipid-lowering therapies on liver outcomes alongside their therapeutic implications in NAFLD/NASH are critically discussed. Preclinical and clinical evidence suggests that statins reduce hepatic steatosis, inflammation and fibrosis in patients with NAFLD/NASH. Most data are derived from observational and small prospective clinical studies using changes in liver enzyme activities, steatosis/fibrosis scores, and imaging evidence of steatosis as surrogates. Also, relevant histologic benefits were noted in small biopsy studies. Atorvastatin and rosuvastatin showed greater benefits, whereas data for other statins are scarce and sometimes conflicting. Similar studies to those of statins showed efficacy of ezetimibe against hepatic steatosis. However, no significant anti-inflammatory and anti-fibrotic actions of ezetimibe have been shown. Preclinical studies showed that fibrates through peroxisome proliferator-activated receptor (PPAR)α activation may have a role in NAFLD prevention and management. Nevertheless, no relevant benefits have been noted in human studies. Species-related differences in PPARα expression and its activation responsiveness may help explain this discrepancy. Omega-3 fatty acids reduced hepatic steatosis in numerous heterogeneous studies, but their benefits on hepatic inflammation and fibrosis have not been established. Promising preliminary data for the highly purified eicosapentaenoic acid require further confirmation. Observational studies suggest that proprotein convertase subtilisin/kexin9 inhibitors may also have a role in the management of NAFLD, though this needs to be established by future prospective studies.
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Affiliation(s)
- Ismini Tzanaki
- School of Medicine, European University Cyprus, Nicosia, Cyprus, Nicosia 2404, Cyprus
| | - Aris P Agouridis
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus
| | - Michael S Kostapanos
- General Medicine, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge CB20QQ, United Kingdom
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van den Hoek AM, de Jong JCBC, Worms N, van Nieuwkoop A, Voskuilen M, Menke AL, Lek S, Caspers MPM, Verschuren L, Kleemann R. Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk. Metabolism 2021; 124:154873. [PMID: 34478753 DOI: 10.1016/j.metabol.2021.154873] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 08/25/2021] [Accepted: 08/28/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Non-alcoholic steatohepatitis (NASH) has become one of the most common liver diseases and is still without approved pharmacotherapy. Lifestyle interventions using exercise and diet change remain the current treatment of choice and even a small weight loss (5-7%) can already have a beneficial effect on NASH. However, the underlying molecular mechanisms of exercise and diet interventions remain largely elusive, and it is unclear whether they exert their health effects via similar or different pathways. METHODS Ldlr-/-.Leiden mice received a high fat diet (HFD) for 30 weeks to establish a severe state of NASH/fibrosis with simultaneous atherosclerosis development. Groups of mice were then either left untreated (control group) or were treated for 20 weeks with exercise (running wheel), diet change (switch to a low fat chow diet) or the combination thereof. The liver and distant organs including heart, white adipose tissue (WAT) and muscle were histologically examined. Comprehensive transcriptome analysis of liver, WAT and muscle revealed the organ-specific effects of exercise and diet and defined the underlying pathways. RESULTS Exercise and dietary change significantly reduced body weight, fat mass, adipocyte size and improved myosteatosis and muscle function with additive effects of combination treatment. WAT inflammation was significantly improved by diet change, tended to be reduced with exercise, and combination therapy had no additive effect. Hepatic steatosis and inflammation were almost fully reversed by exercise and diet change, while hepatic fibrosis tended to be improved with exercise and was significantly improved with diet change. Additive effects for the combination therapy were shown for liver steatosis and associated liver lipids, and atherosclerosis, but not for hepatic inflammation and fibrosis. Pathway analysis revealed complementary effects on metabolic pathways and lipid handling processes, thereby substantiating the added value of combined lifestyle treatment. CONCLUSIONS Exercise, diet change and the combination thereof can reverse established NASH/fibrosis in obese Ldlr-/-.Leiden mice. In addition, the lifestyle interventions had beneficial effects on atherosclerosis, WAT inflammation and muscle function. For steatosis and other parameters related to adiposity or lipid metabolism, exercise and dietary change affected more distinct pathways that acted complementary when the interventions were combined resulting in an additive effect for the combination therapy on important endpoints including NASH and atherosclerosis. For inflammation, exercise and diet change shared several underlying pathways resulting in a net similar effect when the interventions were combined.
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MESH Headings
- Adipose Tissue, White/metabolism
- Adipose Tissue, White/pathology
- Animals
- Atherosclerosis/diet therapy
- Atherosclerosis/genetics
- Atherosclerosis/pathology
- Atherosclerosis/therapy
- Diet, Fat-Restricted
- Diet, High-Fat
- Lipid Metabolism
- Liver/metabolism
- Liver/pathology
- Liver Cirrhosis/diet therapy
- Liver Cirrhosis/pathology
- Liver Cirrhosis/therapy
- Mice
- Mice, Knockout
- Muscle, Skeletal/metabolism
- Muscle, Skeletal/pathology
- Non-alcoholic Fatty Liver Disease/diet therapy
- Non-alcoholic Fatty Liver Disease/genetics
- Non-alcoholic Fatty Liver Disease/pathology
- Non-alcoholic Fatty Liver Disease/therapy
- Physical Conditioning, Animal/physiology
- Receptors, LDL/genetics
- Receptors, LDL/metabolism
- Signal Transduction/physiology
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Affiliation(s)
- Anita M van den Hoek
- Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, the Netherlands.
| | - Jelle C B C de Jong
- Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, the Netherlands; Human and Animal Physiology, Wageningen University, Wageningen, the Netherlands
| | - Nicole Worms
- Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, the Netherlands
| | - Anita van Nieuwkoop
- Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, the Netherlands
| | - Marijke Voskuilen
- Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, the Netherlands
| | - Aswin L Menke
- Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, the Netherlands
| | - Serene Lek
- Clinnovate Health UK Ltd, Glasgow, United Kingdom
| | - Martien P M Caspers
- Department of Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), Zeist, the Netherlands
| | - Lars Verschuren
- Department of Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), Zeist, the Netherlands
| | - Robert Kleemann
- Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, the Netherlands; Department of Vascular Surgery, Leiden University Medical Center, Leiden (LUMC), the Netherlands
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Ji Y, Lee H, Kaura S, Yip J, Sun H, Guan L, Han W, Ding Y. Effect of Bariatric Surgery on Metabolic Diseases and Underlying Mechanisms. Biomolecules 2021; 11:1582. [PMID: 34827579 PMCID: PMC8615605 DOI: 10.3390/biom11111582] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 10/11/2021] [Accepted: 10/15/2021] [Indexed: 12/17/2022] Open
Abstract
Obesity is a highly prevalent public health concern, attributed to multifactorial causes and limited in treatment options. Several comorbidities are closely associated with obesity such as the development of type 2 diabetes mellitus (T2DM), cardiovascular and cerebrovascular diseases, and nonalcoholic fatty liver disease (NAFLD). Bariatric surgery, which can be delivered in multiple forms, has been remarked as an effective treatment to decrease the prevalence of obesity and its associated comorbidities. The different types of bariatric surgery create a variety of new pathways for food to metabolize in the body and truncate the stomach's caliber. As a result, only a small quantity of food is tolerated, and the body mass index noticeably decreases. This review describes the improvements of obesity and its comorbidities following bariatric surgery and their mechanism of improvement. Additionally, endocrine function improvements after bariatric surgery, which contributes to the patients' health improvement, are described, including the role of glucagon-like peptide-1 (GLP-1), fibroblast growth factors 19 and 21 (FGF-19, FGF-21), and pancreatic peptide YY (PYY). Lastly, some of the complications of bariatric surgery, including osteoporosis, iron deficiency/anemia, and diarrhea, as well as their potential mechanisms, are described.
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Affiliation(s)
- Yu Ji
- Department of General Surgery, Beijing Luhe Clinical Institute, Capital Medical University, Beijing 101149, China;
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.L.); (S.K.); (L.G.); (Y.D.)
- John D. Dingell VA Medical Center, 4646 John R Street (11R), Detroit, MI 48201, USA
| | - Hangil Lee
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.L.); (S.K.); (L.G.); (Y.D.)
| | - Shawn Kaura
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.L.); (S.K.); (L.G.); (Y.D.)
| | - James Yip
- Department of General Surgery, Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Hao Sun
- Central Laboratory, Beijing Luhe Clinical Institute, Capital Medical University, Beijing 101149, China;
| | - Longfei Guan
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.L.); (S.K.); (L.G.); (Y.D.)
- John D. Dingell VA Medical Center, 4646 John R Street (11R), Detroit, MI 48201, USA
- Department of General Surgery, Wayne State University School of Medicine, Detroit, MI 48201, USA;
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China
| | - Wei Han
- Department of General Surgery, Beijing Luhe Clinical Institute, Capital Medical University, Beijing 101149, China;
| | - Yuchuan Ding
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.L.); (S.K.); (L.G.); (Y.D.)
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Shan MY, Dai Y, Ren XD, Zheng J, Zhang KB, Chen B, Yan J, Xu ZH. Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2021; 19:545-554. [PMID: 34686466 DOI: 10.1016/j.joim.2021.09.003] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 05/31/2021] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To investigate effects of berberine (BBR) on cholesterol synthesis in HepG2 cells with free fatty acid (FFA)-induced steatosis and to explore the underlying mechanisms. METHODS A steatosis cell model was induced in HepG2 cell line fed with FFA (0.5 mmol/L, oleic acid:palmitic acid = 2:1), and then treated with three concentrations of BBR; cell viability was assessed with cell counting kit-8 assays. Lipid accumulation in cells was observed through oil red O staining and total cholesterol (TC) content was detected by TC assay. The effects of BBR on cholesterol synthesis mediators were assessed by Western blotting and quantitative polymerase chain reaction. In addition, both silent information regulator 1 (SIRT1) and forkhead box transcription factor O1 (FoxO1) inhibitors were employed for validation. RESULTS FFA-induced steatosis was successfully established in HepG2 cells. Lipid accumulation and TC content in BBR groups were significantly lower (P < 0.05, P < 0.01), associated with significantly higher mRNA and protein levels of SIRT1(P < 0.05, P < 0.01), significantly lower sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy 3-methylglutaryl-CoA reductase levels (P < 0.05, P < 0.01), as well as higher Acetyl-FoxO1 protein level (P < 0.05, P < 0.01) compared to the FFA only group. Both SIRT1 inhibitor SIRT1-IN-1 and FoxO1 inhibitor AS1842856 blocked the BBR-mediated therapeutic effects. Immunofluorescence showed that the increased SIRT1 expression increased FoxO1 deacetylation, and promoted its nuclear translocation. CONCLUSION BBR can mitigate FFA-induced steatosis in HepG2 cells by activating SIRT1-FoxO1-SREBP2 signal pathway. BBR may emerge as a potential drug candidate for treating nonalcoholic hepatic steatosis.
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Affiliation(s)
- Meng-Ya Shan
- Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Ying Dai
- Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Xiao-Dan Ren
- Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Jing Zheng
- Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Ke-Bin Zhang
- National Drug Clinical Trail Institution, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Bin Chen
- Department of Biochemistry and Molecular Biology, Army Medical University, Chongqing 400038, China
| | - Jun Yan
- Department 1, Research Institute of Surgery & Daping Hospital, Army Medical Center of Chinese People's Liberation Army, Army Medical University, Chongqing 400042, China
| | - Zi-Hui Xu
- Department of Integrative Medicine, Xinqiao Hospital, Army Medical University, Chongqing 400037, China.
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Gao Y, Tian R, Liu H, Xue H, Zhang R, Han S, Ji L, Huang W, Zhan J, You Y. Research progress on intervention effect and mechanism of protocatechuic acid on nonalcoholic fatty liver disease. Crit Rev Food Sci Nutr 2021; 62:9053-9075. [PMID: 34142875 DOI: 10.1080/10408398.2021.1939265] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become a surge burden worldwide due to its high prevalence, with complicated deterioration symptoms such as liver fibrosis and cancer. No effective drugs are available for NALFD so far. The rapid growth of clinical demand has prompted the treatment of NAFLD to become a research hotspot. Protocatechuic acid (PCA) is a natural secondary metabolite commonly found in fruits, vegetables, grains, and herbal medicine. It is also the major internal metabolites of anthocyanins and other polyphenols. In the present manuscript, food sources, metabolic absorption, and efficacy of PCA were summarized while analyzing its role in improving NAFLD, as well as the mechanism involved. The results indicated that PCA could ameliorate NAFLD by regulating glucose and lipid metabolism, oxidative stress and inflammation, gut microbiota and metabolites. It was proposed for the first time that PCA might reduce NAFLD by enhancing the energy consumption of brown adipose tissue (BAT). However, the PCA administration mode and dose for NAFLD remain inconclusive. Fresh insights into the specific molecular mechanisms are required, while clinical trials are essential in the future. This review provides new targets and reasoning for the clinical application of PCA in the prevention and treatment of NAFLD.
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Affiliation(s)
- Yunxiao Gao
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Rongrong Tian
- Department of Biomedicine, Beijing City University, Beijing, China
| | - Haiyue Liu
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Huimin Xue
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Ruizhe Zhang
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Suping Han
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Lin Ji
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Weidong Huang
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Jicheng Zhan
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Yilin You
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
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Naghibeiranvand M, Visskaramian A, Mehrabirad F, Mohammadi Z. Comparison of Body Mass Index, Smoking, Vitamin E and Type of Oil Consumed Between Patients Suffering from Non-alcoholic Fatty Liver Disease Versus Non-affected Patients: A Case-Control Study. JUNDISHAPUR JOURNAL OF CHRONIC DISEASE CARE 2021; 10. [DOI: 10.5812/jjcdc.108713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) has an increasing trend in the world and can lead to liver failure and death if left untreated. Lifestyle modification is very important in the treatment of this disease. Objectives: This study aimed to determine the comparison of body mass index (BMI), smoking, vitamin E consumption, and type of oil consumed by patients with NAFLD with non-alcoholic patients. Methods: The present study was a retrospective case-control study that was performed on 120 patients referred to the ultrasound unit of Shohaday Ashayer Hospital in Khorramabad. The participants were divided into two groups, including case (61 people) and control (59 people). The questionnaire consisted of three parts: (1) the first part was related to demographic information; (2) the second part was related to liver ultrasound results; (3) and the third part was related to height, weight, BMI, weekly vitamin E intake, daily smoking status, and type of oil consumed. Data were analyzed using SPSS-23 software and descriptive and inferential statistical methods. Results: Most of the participants in the study were 69 (55.8%) and 92 (76.66%) were married. The mean BMI of patients with NAFLD was significantly higher than non-alcoholic patients (P = 0.003). There was no statistically significant difference in daily smoking and weekly intake of vitamin E in patients with and without non-alcoholic fatty liver disease (P < 0.05). According to Fisher's exact test, it was found that there was a statistically significant difference in the frequency by patients with NAFLD and non-alcoholic (P = 0.014). Also, a statistically significant difference was observed in the frequency of the type of oil consumed by patients with NAFLD (P = 0.014). Conclusions: Consumption of olive and sesame oil along with weight loss is recommended. Smoking as a risk factor, as well as the use of vitamin E to prevent and treat NAFLD, require further studies with a larger sample size.
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Epigenetics in NAFLD/NASH: Targets and therapy. Pharmacol Res 2021; 167:105484. [PMID: 33771699 DOI: 10.1016/j.phrs.2021.105484] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 02/02/2021] [Accepted: 02/03/2021] [Indexed: 12/15/2022]
Abstract
Recently non-alcoholic fatty liver disease (NAFLD) has grabbed considerable scientific attention, owing to its rapid increase in prevalence worldwide and growing burden on end-stage liver diseases. Metabolic syndrome including obesity, diabetes, and hypertension poses a grave risk to NAFLD etiology and progression. With no drugs available, the mainstay of NAFLD management remains lifestyle changes with exercise and dietary modifications. Nonselective drugs such as metformin, thiazolidinediones (TZDs), ursodeoxycholic acid (UDCA), silymarin, etc., are also being used to target the interrelated pathways for treating NAFLD. Considering the enormous disease burden and the unmet need for drugs, fresh insights into pathogenesis and drug discovery are required. The emergence of the field of epigenetics offers a convincing explanation for the basis of lifestyle, environmental, and other risk factors to influence NAFLD pathogenesis. Therefore, understanding these epigenetic modifications to target the primary cause of the disease might prove a rational strategy to prevent the disease and develop novel therapeutic interventions. Apart from describing the role of epigenetics in the pathogenesis of NAFLD as in other reviews, this review additionally provides an elaborate discussion on exploiting the high plasticity of epigenetic modifications in response to environmental cues, for developing novel therapeutics for NAFLD. Besides, this extensive review provides evidence for epigenetic mechanisms utilized by several potential drugs for NAFLD.
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Quantitative, noninvasive MRI characterization of disease progression in a mouse model of non-alcoholic steatohepatitis. Sci Rep 2021; 11:6105. [PMID: 33731798 PMCID: PMC7971064 DOI: 10.1038/s41598-021-85679-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 02/28/2021] [Indexed: 12/17/2022] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is an increasing cause of chronic liver disease characterized by steatosis, inflammation, and fibrosis which can lead to cirrhosis, hepatocellular carcinoma, and mortality. Quantitative, noninvasive methods for characterizing the pathophysiology of NASH at both the preclinical and clinical level are sorely needed. We report here a multiparametric magnetic resonance imaging (MRI) protocol with the fibrogenesis probe Gd-Hyd to characterize fibrotic disease activity and steatosis in a common mouse model of NASH. Mice were fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) to induce NASH with advanced fibrosis. Mice fed normal chow and CDAHFD underwent MRI after 2, 6, 10 and 14 weeks to measure liver T1, T2*, fat fraction, and dynamic T1-weighted Gd-Hyd enhanced imaging of the liver. Steatosis, inflammation, and fibrosis were then quantified by histology. NASH and fibrosis developed quickly in CDAHFD fed mice with strong correlation between morphometric steatosis quantification and liver fat estimated by MRI (r = 0.90). Sirius red histology and collagen quantification confirmed increasing fibrosis over time (r = 0.82). Though baseline T1 and T2* measurements did not correlate with fibrosis, Gd-Hyd signal enhancement provided a measure of the extent of active fibrotic disease progression and correlated strongly with lysyl oxidase expression. Gd-Hyd MRI accurately detects fibrogenesis in a mouse model of NASH with advanced fibrosis and can be combined with other MR measures, like fat imaging, to more accurately assess disease burden.
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Rim JH, Youk T, Gee HY, Cho J, Yoo J. Dynamic Chronological Changes in Serum Triglycerides Are Associated With the Time Point for Non-alcoholic Fatty Liver Disease Development in the Nationwide Korean Population Cohort. Front Med (Lausanne) 2021; 8:637241. [PMID: 33777980 PMCID: PMC7987649 DOI: 10.3389/fmed.2021.637241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 01/29/2021] [Indexed: 12/02/2022] Open
Abstract
Background: We investigated the effects of anthropometric, laboratory, and lifestyle factors on the development of non-alcoholic fatty liver disease (NAFLD) in a nationwide, population-based, 4-year retrospective cohort. Methods: The propensity score-matched study and control groups contained 1,474 subjects who had data in the Korean National Health Insurance Service-National Sample Cohort in 2009, 2011, and 2013. NAFLD was defined using medical records of a diagnosis confirmed by primary clinicians and meeting two previously validated fatty liver prediction models. Chronological changes in anthropometric variables, laboratory results, and lifestyle factors during two periods were compared between patient and control groups in order to find out parameters with consistent dynamics in pre-NAFLD stage which was defined as period just before the NAFLD development. Results: Among the 5 anthropometric, 10 laboratory, and 3 lifestyle factors, prominent chronological decremental changes in serum triglycerides were consistently observed during the pre-NAFLD stage, although the degrees of changes were more predominant in men (−9.46 mg/dL) than women (−5.98 mg/dL). Furthermore, weight and waist circumference changes during the pre-NAFLD stage were noticeable only in women (+0.36 kg and +0.9 cm for weight and waist circumference, respectively), which suggest gender difference in NAFLD. Conclusion: Early screening strategies for people with abrupt chronological changes in serum triglycerides to predict NAFLD development before the progression is recommended.
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Affiliation(s)
- John Hoon Rim
- Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, South Korea.,Department of Medicine, Physician-Scientist Program, Yonsei University Graduate School of Medicine, Seoul, South Korea.,Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea
| | - Taemi Youk
- Research Institute, National Health Insurance Service Ilsan Hospital, Goyang, South Korea.,Department of Statistics, Korea University, Seoul, South Korea
| | - Heon Yung Gee
- Department of Medicine, Physician-Scientist Program, Yonsei University Graduate School of Medicine, Seoul, South Korea.,Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea
| | - Jooyoung Cho
- Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, South Korea.,Department of Laboratory Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Jongha Yoo
- Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, South Korea.,Department of Laboratory Medicine, National Health Insurance Service Ilsan Hospital, Goyang, South Korea
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Le Carbone prevents liver damage in non-alcoholic steatohepatitis-hepatocellular carcinoma mouse model via AMPKα-SIRT1 signaling pathway activation. Heliyon 2021; 7:e05888. [PMID: 33490669 PMCID: PMC7803657 DOI: 10.1016/j.heliyon.2020.e05888] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/30/2020] [Accepted: 12/24/2020] [Indexed: 12/12/2022] Open
Abstract
Le Carbone (LC), a fiber-enriched activated charcoal dietary supplement, claimed to be effective against inflammation associated with colitis, trimethylaminuria, and sclerosis. The study aimed to investigate the underlying mechanisms of LC to protect liver damage and its progression in non-alcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mice. To induce this model, C57BL/6J male baby mice were injected with a low-dose of streptozotocin and fed with a high-fat diet (HFD) 32 during 4 weeks–16 weeks of age. The LC suspension was administered orally at a dose of 5 mg/mouse/day started at the age of 6 weeks and continued until 16 weeks of age along with HFD32 feeding. At the end of the experiment, serum and liver tissues were collected for the biochemical, histological, and molecular analysis. We found that LC suspension improved the histopathological changes, serum aminotransferases in NASH mice. The hepatic expression of metabolic proteins, p-AMPKα and sirtuin 1, and proteins responsible for β-oxidation of fatty acids, peroxisome proliferator-activated receptor (PPAR) γ coactivator-α, PPARα were significantly repressed in NASH mice. LC treatment markedly restored these expressions. LC treatment significantly reduced the hepatic proteins expressions of PPARγ, tissue inhibitor of metalloproteinases 4, p47phox, p-JNK, p-ERK1/2, glypican-3, and prothrombin in NASH mice. Our findings demonstrate that LC prevents the liver damage and progression of NASH, possibly by enhancing the AMPK-SIRT1 signaling pathway.
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Nestor JJ, Zhang X, Jaw‐Tsai S, Parkes DG, Becker CK. Design and characterization of a surfactant‐conjugated, long‐acting, balanced
GLP
‐1/glucagon receptor dual agonist. Pept Sci (Hoboken) 2021. [DOI: 10.1002/pep2.24221] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- John J. Nestor
- Spitfire Pharma, Inc. South San Francisco California USA
| | - Xiaoming Zhang
- Velocity Pharmaceutical Development LLC South San Francisco California USA
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Readiness for the epidemic: The adult nonalcoholic fatty liver disease toolkit for primary care nurse practitioners. J Am Assoc Nurse Pract 2020; 32:323-331. [PMID: 31274677 DOI: 10.1097/jxx.0000000000000223] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND PURPOSE Nonalcoholic fatty liver disease (NAFLD) prevalence has reached epidemic proportions, and the severe form, nonalcoholic steatohepatitis, can result in cirrhosis and liver failure. The growing prevalence requires primary care (PC) providers to be adept at recognition and management; however, they experience significant knowledge gaps that can result in delayed access to interventions that could improve outcomes. This study's aim was to develop and evaluate a toolkit to improve knowledge gaps and support evidence-based practice (EBP) among PC nurse practitioners caring for patients with NAFLD in a midwestern state. METHODS AND INTERVENTION The Adult NAFLD Toolkit was designed using the Knowledge to Action framework and guidelines from the Agency for Healthcare Research and Quality. The success of the toolkit was evaluated by administering the NAFLD survey for general practitioners in a pre-post evaluation design. RESULTS Pre-post survey scores (N = 11) were compared for statistically significant change using the Wilcoxon signed rank test for matched pairs and showed improvement in overall knowledge (p = .011), perceived preparedness to care for NAFLD (p = .007), intention to recommend weight loss for management (p = .008), and intention to use the NAFLD fibrosis score for patient monitoring (p = .008). CONCLUSIONS The results of this pilot study demonstrate successful implementation and positive outcomes of an EBP toolkit and support its expanded use. Continued evaluation on a larger scale is needed. Health care providers can use the process described in this article to develop and implement toolkits to support EBP of other PC issues.
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Abstract
OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) is a global epidemic without effective therapeutic agents in the clinic. This meta-analysis aimed to assess the efficacy of the marketed hepatoprotectant bicyclol at improving blood biomarkers in patients with NAFLD. DESIGN Electronic databases were searched for randomised controlled trials (RCTs) published up to August 2020 using bicyclol to treat NAFLD. The risk of bias, quality of evidence and publication bias were evaluated. Blood biomarkers, including alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), triglyceride (TG) and total cholesterol (TC), were analysed using Review Manager V.5.3 software. Outcomes with significant heterogeneity (I2 ≥75%) were divided into the bicyclol monotherapy subgroup and combination treatment subgroup. RESULTS Twelve RCTs involving 1008 patients were finally included. No serious adverse events were reported in the bicyclol-treated groups. The total effective rate of bicyclol intervention for NAFLD was significantly higher than that of the control group. The decreases in the levels of AST (mean difference (MD) = -15.20; 95% CI -20.51 to -9.90; I2=74%), TBIL (MD = -1.72; 95% CI -2.72 to -0.72; I2=0%) and TC (MD = -0.52; 95% CI -0.70 to -0.34; I2=67%) treated by bicyclol were significantly higher than those in the control group. When a high heterogeneity existed (I2 ≥75%), subgroup analyses were conducted and revealed significantly decreased ALT levels (MD = -34.07; 95% CI -36.70 to -31.43; I2=0%) merely in the bicyclol monotherapy subgroup, while TG level (MD = -0.39; 95% CI -0.45 to -0.33; I2=0%) was decreased in the bicyclol combination therapy subgroup. CONCLUSIONS The study presents the evidence of bicyclol monotherapy and/or combination therapy for improving liver function and blood lipid biomarkers in patients with NAFLD. This preliminary study predicts that bicyclol might be an alternative drug for NAFLD therapy in the future.
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Affiliation(s)
- Hu Li
- CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nan-Nan Liu
- CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zong-Gen Peng
- CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Prabhakar O, Bhuvaneswari M. Role of diet and lifestyle modification in the management of nonalcoholic fatty liver disease and type 2 diabetes. Tzu Chi Med J 2020; 33:135-145. [PMID: 33912410 PMCID: PMC8059462 DOI: 10.4103/tcmj.tcmj_86_20] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 05/11/2020] [Accepted: 06/08/2020] [Indexed: 12/15/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic evidence of insulin resistance which is the hallmark of type 2 diabetes. NAFLD is considered as the risk factor for developing type 2 diabetes and has a high frequency of occurrence in those with existing type 2 diabetes. Compared with patients with only NAFLD or type 2 diabetes, these patients show a poor metabolic profile and increase mortality. Hence, effective treatment strategies are necessary. Here, we review the role of diet and lifestyle modification in the management of NAFLD and type 2 diabetes. Based on the available studies, it has been shown that the addition of any kind of physical activity or exercise is beneficial for patients with both NAFLD and type 2 diabetes. Proper dietary management leads to weight loss are also effective in improving metabolic parameters in patients with both NAFLD and type 2 diabetes. In conclusion, it is clear that increasing physical activity or exercise is effective in improving metabolic parameters in patients who are suffering with both NAFLD and type 2 diabetes.
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Affiliation(s)
- Orsu Prabhakar
- Department of Pharmacology, GITAM Institute of Pharmacy, Visakhapatnam, Andhra Pradesh, India
| | - Mylipilli Bhuvaneswari
- Department of Pharmacology, GITAM Institute of Pharmacy, Visakhapatnam, Andhra Pradesh, India
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Jalili R, Somi MH, Hosseinifard H, Salehnia F, Ghojazadeh M, Makhdami N, Shirmohammadi M. The Evaluation of Effective Drugs for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis. Adv Pharm Bull 2020; 10:542-555. [PMID: 33072533 PMCID: PMC7539311 DOI: 10.34172/apb.2020.065] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 01/07/2020] [Accepted: 01/27/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis are two forms of fatty liver disease with benign and malignant nature, respectively. These two conditions can cause an increased risk of liver cirrhosis and hepatocellular carcinoma. Given the importance and high prevalence of NAFLD, it is necessary to investigate the results of different studies in related scope to provide a clarity guarantee of effectiveness. Therefore, this systematic review and meta-analysis aim to study the efficacy of various medications used in the treatment of NAFLD. Methods: A systematic search of medical databases identified 1963 articles. After exclusion of duplicated articles and those which did not meet our inclusion criteria, eta-analysis was performed on 84 articles. Serum levels of alanine aminotransferase (ALT), aspartate amino transferase (AST) were set as primary outcomes and body mass index (BMI), hepatic steatosis, and NAFLD activity score (NAS) were determined as secondary outcomes. Results: Based on the P-score of the therapeutic effects on the non-alcoholic steatohepatitis (NASH), we observed the highest efficacy for atorvastatin, tryptophan, orlistat, omega-3 and obeticholic acid for reduction of ALT, AST, BMI, steatosis and NAS respectively. Conclusion: This meta-analysis showed that atorvastatin. life-style modification, weight loss, and BMI reduction had a remarkable effect on NAFLD-patients by decreasing aminotransferases.
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Affiliation(s)
- Ramin Jalili
- Department of Internal Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Hossein Somi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Hosseinifard
- Research Center for Evidence Based Medicine (RCEBM), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Salehnia
- Research Center for Evidence Based Medicine (RCEBM), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Morteza Ghojazadeh
- Research Center for Evidence Based Medicine (RCEBM), Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Masoud Shirmohammadi
- Department of Gastroenterology, Liver, and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Klaebel JH, Rakipovski G, Andersen B, Lykkesfeldt J, Tveden-Nyborg P. Dietary Intervention Accelerates NASH Resolution Depending on Inflammatory Status with Minor Additive Effects on Hepatic Injury by Vitamin E Supplementation. Antioxidants (Basel) 2020; 9:antiox9090808. [PMID: 32882802 PMCID: PMC7555643 DOI: 10.3390/antiox9090808] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 08/20/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
Despite the lack of effective pharmacotherapy against nonalcoholic steatohepatitis (NASH) and liver fibrosis, vitamin E (vitE) supplementation and lifestyle modifications are recommended for the management of NASH due to promising clinical results. We recently reported a positive effect of supplementation with 800 IU vitE and atorvastatin on NASH resolution in guinea pigs. In the present study, we investigated the effect of high-dose vitE therapy combined with dietary intervention against progressive NASH and advanced fibrosis in the guinea pig model. Sixty-six guinea pigs received either high-fat (HF) or standard guinea pig chow diet (Control) for 25 weeks. Prior to eight weeks of intervention, HF animals were allocated into groups; dietary intervention (Chow) or dietary intervention with 2000 IU/d vitE supplementation (CvitE). Both Chow and CvitE reduced dyslipidemia, hepatic lipid accumulation and liver weight (p < 0.05), while CvitE further decreased hepatocellular ballooning (p < 0.05). Subanalyses of individual responses within intervention groups showed significant correlation between the hepatic hallmarks of NASH and lipid accumulation vs. inflammatory state (p < 0.05). Collectively, our results indicate that individual differences in sensitivity towards intervention and inflammatory status determine the potential beneficial effect of dietary intervention and high-dose vitE supplementation. Moreover, the study suggests that inflammation is a primary target in NASH treatment.
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Affiliation(s)
- Julie Hviid Klaebel
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark; (J.H.K.); (J.L.)
| | - Günaj Rakipovski
- CV Research, Global Research, Novo Nordisk A/S, Novo Nordisk Park 1, 2670 Måløv, Denmark;
| | - Birgitte Andersen
- Liver Disease Research, Global Research, Novo Nordisk A/S, Novo Nordisk Park 1, 2670 Måløv, Denmark;
| | - Jens Lykkesfeldt
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark; (J.H.K.); (J.L.)
| | - Pernille Tveden-Nyborg
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1870 Frederiksberg C, Denmark; (J.H.K.); (J.L.)
- Correspondence: ; Tel.: +45-353-331-67
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Sanai FM, Abaalkhail F, Hasan F, Farooqi MH, Nahdi NA, Younossi ZM. Management of nonalcoholic fatty liver disease in the Middle East. World J Gastroenterol 2020; 26:3528-3541. [PMID: 32742124 PMCID: PMC7366060 DOI: 10.3748/wjg.v26.i25.3528] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 05/15/2020] [Accepted: 06/10/2020] [Indexed: 02/06/2023] Open
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) in the Middle East is increasing in parallel to an increase in the prevalence of associated risk factors such as obesity, metabolic syndrome, and type 2 diabetes mellitus. About 20% to 30% of the patients progress to develop nonalcoholic steatohepatitis (NASH), a histological subtype of NAFLD, with features of hepatocyte injury such as hepatocyte ballooning. NASH can progress to fibrosis, cirrhosis, and even hepatocellular carcinoma. NAFLD thus causes a substantial burden on healthcare systems and it is imperative that appropriate strategies are discussed at a regional level to facilitate effective management tailored to the needs of the region. To fulfil this unmet need, expert gastroenterologists, hepatologists, and endocrinologists from the region came together in three advisory board meetings that were conducted in Saudi Arabia, United Arab Emirates, and Kuwait, to discuss current local challenges in NAFLD screening and diagnosis, and the different available management options. The experts discussed the disease burden of NAFLD/NASH in the Middle East; screening, diagnosis, and referral patterns in NAFLD; and available treatment options for NAFLD and NASH. This paper summarizes the discussions and opinion of the expert panel on the management of NAFLD/NASH and also presents an extensive literature review on the topic.
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Affiliation(s)
- Faisal M Sanai
- Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah 21423, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- Department of Liver Transplant, King Fahad Specialist Hospital, Dammam 32253, Saudi Arabia
| | - Fuad Hasan
- Department of Internal Medicine, Faculty of Medicine, Kuwait University, Safat 13110, Kuwait
| | | | - Nawal Al Nahdi
- Department of Gastroenterology and Hepatology, Dubai Health Authority, Rashid hospital, Dubai 00000, United Arab Emirates
| | - Zobair M Younossi
- Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA 22042, United States
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Lv X, Dong Y, Hu L, Lu F, Zhou C, Qin S. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the management of nonalcoholic fatty liver disease (NAFLD): A systematic review. Endocrinol Diabetes Metab 2020; 3:e00163. [PMID: 32704576 PMCID: PMC7375121 DOI: 10.1002/edm2.163] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 04/19/2020] [Accepted: 05/23/2020] [Indexed: 12/18/2022] Open
Abstract
There are no licensed drugs for nonalcoholic fatty liver disease (NAFLD), and there is a lack of consensus on the best outcome measures for controlled trials. This systematic review aimed to evaluate the efficacy of GLP-1 RAs in the management of NAFLD, the degree of heterogeneity in trial design and the robustness of conclusions drawn from these clinical trials. We searched publication databases and clinical trial registries through 2 November 2019 for clinical trials with NAFLD. We evaluated improvements in histological findings, noninvasive markers of hepatic steatosis, inflammation, and fibrosis, insulin resistance and anthropometric measures. Our final analysis included 24 clinical trials, comprising 6313 participants with a mean duration of 37 weeks. Four clinical trials, including RCT (n = 1), single-arm studies (n = 2) and case series studies (n = 1), used biopsy-confirmed liver histological change as their end-points. The remaining studies (n = 20) used surrogate end-points. GLP-1 RAs were effective for the improvement in hepatic inflammation, hepatic steatosis and fibrosis. More importantly, GLP-1 RAs showed promise in improving the histological features of NASH. In addition, 8 ongoing trials were identified. In this systematic review of published and ongoing clinical trials of the efficacy of GLP-1RAs for NAFLD, we found that GLP-1 RAs are effective for hepatic steatosis and inflammation, with the potential to reverse fibrosis. Further prospective studies of sufficient duration using histological end-points are needed to fully assess the efficacy of GLP-1 RAs in the management of NAFLD.
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Affiliation(s)
- Xiaodan Lv
- Department of EndocrinologyChina‐Japan Union Hospital of Jilin UniversityChangchunChina
| | - Yongqiang Dong
- Department of Thyroid SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
| | - Lingling Hu
- Department of EndocrinologyNingbo Medical Center Lihuili Eastern HospitalZhejiangChina
| | - Feiyu Lu
- Department of PaediatricsThe First Hospital of Jilin UniversityChangchunChina
| | - Changyu Zhou
- Department of Gastroenterology and HepatologyChina‐Japan Union Hospital of Jilin UniversityChangchunChina
| | - Shaoyou Qin
- Department of Gastroenterology and HepatologyChina‐Japan Union Hospital of Jilin UniversityChangchunChina
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Ma P, Sun C, Li W, Deng W, Adu‐Frimpong M, Yu J, Xu X. Extraction and structural analysis of Angelica sinensis polysaccharide with low molecular weight and its lipid-lowering effect on nonalcoholic fatty liver disease. Food Sci Nutr 2020; 8:3212-3224. [PMID: 32724586 PMCID: PMC7382173 DOI: 10.1002/fsn3.1581] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/22/2020] [Accepted: 03/27/2020] [Indexed: 12/22/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the prevalent and typical chronic liver diseases. In this study, we extracted a novel Angelica sinensis polysaccharide (ASP) with low molecular weight (MW) of 3.2 kDa through optimized "one-step" purification process. The major monosaccharide components of ASP were mannose, rhamnose, glucuronic acid, galactose, arabinose, and xylose with weight ratio of 0.23:0.17:14.41:0.39:1.68:0.87, respectively. Herein, "small" ASP could serve as an effective therapeutic option for NAFLD both in free fatty acid-induced L02 models and in high-fat diet-induced mice models. Results revealed that low MW ASP dose-dependently decreased TG, TC in vitro and TG, TC, ALT, HDL-C, and LDL-C in vivo. Oil Red O-positive area and Nile red fluorescence intensity decreased in ASP treatment groups both in vitro and in vivo which suggested ASP could reduce lipid accumulation and fatty regeneration. Hematoxylin-eosin staining results shown a decrease in hepatocytes ballooning indicating that ASP could ameliorate liver lipid degeneration. Briefly, a novel polysaccharide with low MW was successfully obtained which can prospectively act as NAFLD therapy.
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Affiliation(s)
- Ping Ma
- Key Lab for Drug Delivery and Tissue RegenerationJiangsu Provincial Research Center for Medicinal Function Development of New Food ResourcesSchool of PharmacyJiangsu UniversityZhenjiangChina
| | - Congyong Sun
- Key Lab for Drug Delivery and Tissue RegenerationJiangsu Provincial Research Center for Medicinal Function Development of New Food ResourcesSchool of PharmacyJiangsu UniversityZhenjiangChina
| | - Wenjing Li
- Key Lab for Drug Delivery and Tissue RegenerationJiangsu Provincial Research Center for Medicinal Function Development of New Food ResourcesSchool of PharmacyJiangsu UniversityZhenjiangChina
| | - Wenwen Deng
- Key Lab for Drug Delivery and Tissue RegenerationJiangsu Provincial Research Center for Medicinal Function Development of New Food ResourcesSchool of PharmacyJiangsu UniversityZhenjiangChina
| | - Michael Adu‐Frimpong
- Key Lab for Drug Delivery and Tissue RegenerationJiangsu Provincial Research Center for Medicinal Function Development of New Food ResourcesSchool of PharmacyJiangsu UniversityZhenjiangChina
| | - Jiangnan Yu
- Key Lab for Drug Delivery and Tissue RegenerationJiangsu Provincial Research Center for Medicinal Function Development of New Food ResourcesSchool of PharmacyJiangsu UniversityZhenjiangChina
| | - Ximing Xu
- Key Lab for Drug Delivery and Tissue RegenerationJiangsu Provincial Research Center for Medicinal Function Development of New Food ResourcesSchool of PharmacyJiangsu UniversityZhenjiangChina
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Lorzadeh E, Akhondi-Meybodi M, Mozaffari-Khosravi H, Mirzaei M, Salehi-Abargouei A. Association between empirically derived dietary patterns and liver function tests in adults: Shahedieh cohort study. Nutrition 2020; 81:110897. [PMID: 32738511 DOI: 10.1016/j.nut.2020.110897] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 05/03/2020] [Accepted: 06/06/2020] [Indexed: 12/27/2022]
Abstract
OBJECTIVES Limited data exist on the association between dietary patterns (DPs) and enzymes mainly produced by the liver. This study aimed to examine the relationship between empirically derived DPs and serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transferase (GGT) levels in addition to the alanine/aspartate aminotransferase ratio. METHODS This cross-sectional study was conducted on adults in the baseline phase of the Shahedieh cohort study in Yazd, Iran. Blood samples were taken from participants in a fasted state to provide data on dietary intake and other variables. Major DPs were derived using a principal component analysis. RESULTS In total, 4973 participants (age 46.33 ± 9.08 y) were included in the study. Three DPs were derived: Traditional diet (high in vegetables, fruits, tomatoes, dairy, dried fruits, fruit juice, yogurt, olive and olive oil, sweet desserts, and high-fat dairy products), western diet (high in pizza, refined grains, soft drinks, high-fat dairy products, processed meats, mayonnaise, and snack foods), and hydrogenated fat and sugar diet (high in hydrogenated fat, potatoes, sugars, and legumes). After adjustment for all confounders, the western DP had a significant linear association with serum GGT (P < 0.001). This diet was also associated with higher odds for developing abnormal levels of serum GGT (Ptrend < 0.001). Although the other DPs had some linear associations with enzymes levels, they were not associated with the likelihood for developing abnormally high liver enzymes levels. CONCLUSIONS A higher consumption of a western DP might adversely affect serum GGT levels. Prospective studies are recommended to confirm our results.
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Affiliation(s)
- Elnaz Lorzadeh
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohsen Akhondi-Meybodi
- Department of Internal Medicine, School of Medicine, Shahid Sadoughi General Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Masoud Mirzaei
- Yazd Cardiovascular Research Center, Shahid Sadoughi General Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amin Salehi-Abargouei
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Cui H, Zhang X. Occurrence and clinical management of nonalcoholic fatty liver disease in obesity patients: a literature review. J Pediatr Endocrinol Metab 2020; 33:579-584. [PMID: 32187014 DOI: 10.1515/jpem-2019-0595] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Accepted: 02/19/2020] [Indexed: 01/04/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress-induced liver injury closely correlated with insulin resistance. Currently, the methods for clinical management of NAFLD patients mainly include removing causes, changing lifestyle and dietary structure, drug therapy and weight-loss surgery. This paper summarizes the occurrence and clinical management of NAFLD in patients with obesity, with the aim of formulating scientific clinical interventions for these patients and thus preventing the occurrence of NAFLD.
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Affiliation(s)
- Han Cui
- Department of Endocrinology, Affiliated Dongguan People's Hospital, Southern Medical University (Dongguan People's Hospital), No. 3, South Wandao Road, Xingu Chong, Wanjiang District, Dongguan City, Guangdong Province, China, Phone: +86-13580915733
| | - XiuWei Zhang
- Department of Endocrinology, Affiliated Dongguan People's Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan City, Guangdong Province, China
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Neuschwander-Tetri BA. Therapeutic Landscape for NAFLD in 2020. Gastroenterology 2020; 158:1984-1998.e3. [PMID: 32061596 DOI: 10.1053/j.gastro.2020.01.051] [Citation(s) in RCA: 138] [Impact Index Per Article: 27.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 01/19/2020] [Accepted: 01/21/2020] [Indexed: 12/13/2022]
Abstract
Lifestyle modifications focused on healthy eating and regular exercise are the primary recommendations for patients with nonalcoholic steatohepatitis (NASH). However, for multiple societal, psychological, physical, genetic, and epigenetic reasons, the ability of people to adopt and sustain such changes is challenging and typically not successful. To end the epidemic of NASH and prevent its complications, including cirrhosis and hepatocellular carcinoma, pharmacological interventions are now being evaluated in clinical trials. Treatments include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation and fibrogenesis that lead to cirrhosis. It is likely that patients develop the phenotype of NASH by multiple mechanisms, and thus the optimal treatments of NASH will likely evolve to personalized therapy once we understand the mechanistic underpinnings of NASH in each patient. Reviewed here is the treatment landscape in this rapidly evolving field with an emphasis on drugs in Phase 2 and Phase 3 trials.
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