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Zhang H, Feng S, Song S, Zhao Q, Gao Y, Zhang T. First evidence in the association of phenolic endocrine-disrupting chemicals with secondary non-alcoholic fatty liver disease: A case-control study in South China. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2025; 373:126086. [PMID: 40118363 DOI: 10.1016/j.envpol.2025.126086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 02/12/2025] [Accepted: 03/17/2025] [Indexed: 03/23/2025]
Abstract
The presence of phenolic endocrine disrupting chemicals (EDCs) in patients with secondary non-alcoholic fatty liver disease (S-NAFLD) and their associations with S-NAFLD incidence have not been previously documented. In this study, serum concentrations of 32 phenolic EDCs, including parabens, benzophenone-type UV-filters, bisphenols, and bisphenol A diglycidyl ether derivatives, were detected in patients with S-NAFLD as well as healthy population from South China. These target EDCs were ubiquitous in serum samples from both cohorts. Interestingly, significantly higher (p < 0.05) serum levels of most analytes were detected in individuals with S-NAFLD compared to those in the healthy population. Through multiple modeling analyses, we observed that parabens and bisphenols mixtures were positively associated with S-NAFLD incidence. A list of high-risk EDCs for S-NAFLD-related diseases was identified, including propyl paraben (PrP), butyl paraben (BuP), bisphenol A (BPA), and bisphenol AP (BPAP). Furthermore, significant positive correlations were found between the serum levels of these high-risk analytes and liver clinic indices. To the best of our knowledge, this study firstly examined the serum levels of multiple phenolic EDCs in patients with S-NAFLD, aiming to provide novel insights into high-risk EDCs associated with S-NAFLD incidence and their associations with clinic liver indices.
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Affiliation(s)
- Henglin Zhang
- School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Shuai Feng
- School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Shiming Song
- School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Qing Zhao
- School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Yanxia Gao
- School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Tao Zhang
- School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, China.
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Forouzesh P, Kheirouri S, Alizadeh M. Predicting hepatic steatosis degree in metabolic dysfunction-associated steatotic liver disease using obesity and lipid-related indices. Sci Rep 2025; 15:8612. [PMID: 40074727 PMCID: PMC11904216 DOI: 10.1038/s41598-024-73132-1] [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: 07/10/2024] [Accepted: 09/13/2024] [Indexed: 03/14/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease, represents a prevalent condition ranging from simple steatosis to advanced stages associated with liver cancer. Asymptomatic presentation in the majority of cases underscores the need for non-invasive, cost-effective methods to stratify degree of hepatic steatosis. This cross-sectional study aimed to assess the association between obesity and lipid-related indices with the degree of hepatic steatosis in MASLD patients. 150 individuals recently diagnosed with metabolic dysfunction-associated steatotic liver disease were recruited. Anthropometric measurements, including weight, height, and waist circumference (WC), were taken, alongside biochemical parameters such as alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides (TG), high-density lipoprotein, low-density lipoprotein, and fasting plasma glucose, following a 12-h fasting period. Various indicators of obesity and lipid metabolism, including body mass index, waist-to-height ratio (WHtR), a body shape index, lipid accumulation product (LAP), triglyceride-glucose index (TyG), visceral adiposity index, and hepatic steatosis index (HSI), were calculated. The diagnosis of MASLD and degree of hepatic steatosis were established through abdominal ultrasound examination. Data analysis was performed utilizing SPSS version 22. All the investigated indices displayed an area under the curve (AUC) surpassing 0.5, implying a correlation with the degree of hepatic steatosis. Notably, TyG-WC, TyG-WHtR, LAP, and a cardiometabolic obesity index showed the highest AUC values (> 0.7), indicating a relatively strong association with degree of hepatic steatosis. Specifically, in females, TyG-WC (AUC = 0.797, 95% CI 0.712-0.882, threshold = 865.991), while in males, LAP (AUC = 0.746, 95% CI 0.593-0.899, threshold = 74.290), demonstrated the highest AUC values. TyG-WHtR, TyG-WC, and LAP exhibited significant correlations with the degree of hepatic steatosis. Given their non-invasive nature and easy measurement, they hold promise for potential clinical utility, pending validation in additional studies.
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Affiliation(s)
- Paniz Forouzesh
- Department of Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Attar Nishabouri St., Tabriz, 5166614711, Iran.
| | - Sorayya Kheirouri
- Department of Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Attar Nishabouri St., Tabriz, 5166614711, Iran
| | - Mohammad Alizadeh
- Department of Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Attar Nishabouri St., Tabriz, 5166614711, Iran
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Boel F, Akimov V, Teuchler M, Terkelsen MK, Wernberg CW, Larsen FT, Hallenborg P, Lauridsen MM, Krag A, Mandrup S, Ravnskjær K, Blagoev B. Deep proteome profiling of metabolic dysfunction-associated steatotic liver disease. COMMUNICATIONS MEDICINE 2025; 5:56. [PMID: 40032974 PMCID: PMC11876662 DOI: 10.1038/s43856-025-00780-3] [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: 06/03/2024] [Accepted: 02/21/2025] [Indexed: 03/05/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) affects roughly 1 in 3 adults and is a leading cause of liver transplants and liver related mortality. A deeper understanding of disease pathogenesis is essential to assist in developing blood-based biomarkers. METHODS Here, we use data-independent acquisition mass spectrometry to assess disease-state associated protein profiles in human liver, blood plasma, and white adipose tissue (WAT). RESULTS In liver, we find that MASLD is associated with an increased abundance of proteins involved in immune response and extracellular matrix (ECM) and a decrease in proteins involved in metabolism. Cell type deconvolution of the proteome indicates liver endothelial and hepatic stellate cells are the main source of ECM rearrangements, and hepatocytes are the major contributor to the changes in liver metabolism. In the blood, profiles of several MASLD-associated proteins correlate with expression in WAT rather than liver and so could serve as suitable liver disease predictors in a multi-protein panel marker. Moreover, our proteomics-based logistic regression models perform better than existing methods for predicting MASLD and liver fibrosis from human blood samples. CONCLUSIONS Our comprehensive proteomic analysis deepens the understanding of liver function and MASLD pathology by elucidating key cellular mechanisms and multi-organ interactions, and demonstrates the robustness of a proteomics-based biomarker panel to enhance diagnosis of MASLD and significant fibrosis.
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Affiliation(s)
- Felix Boel
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Vyacheslav Akimov
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Mathias Teuchler
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Mike Krogh Terkelsen
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Charlotte Wilhelmina Wernberg
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
- Department of Gastroenterology and Hepatology, University Hospital of Southern Denmark, Esbjerg, Denmark
| | - Frederik Tibert Larsen
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Philip Hallenborg
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
| | - Mette Munk Lauridsen
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
- Department of Gastroenterology and Hepatology, University Hospital of Southern Denmark, Esbjerg, Denmark
| | - Aleksander Krag
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense M, Denmark
| | - Susanne Mandrup
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Kim Ravnskjær
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark
| | - Blagoy Blagoev
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark.
- Center for Functional Genomics and Tissue Plasticity (ATLAS), University of Southern Denmark, Odense M, Denmark.
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Amirkhizi F, Taghizadeh M, Khalese-Ranjbar B, Hamedi-Shahraki S, Asghari S. The clinical value of serum sirtuin-1 concentration in the diagnosis of metabolic dysfunction-associated steatotic liver disease. BMC Gastroenterol 2025; 25:27. [PMID: 39844087 PMCID: PMC11753077 DOI: 10.1186/s12876-025-03613-8] [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: 08/28/2024] [Accepted: 01/14/2025] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease and can affect individuals without producing any symptoms. We aimed to explore the value of serum sirtuin-1 (Sirt-1) in the diagnosis of MASLD. METHODS This case-control study analyzed data collected from 190 individuals aged 20 to 60 years. Anthropometric parameters, demographic information, and serum biochemical variables-including glycemic parameters, lipid profiles, liver enzymes, and Sirt-1 levels-were assessed. The correlation between serum Sirt-1 and biochemical variables was examined using Pearson's correlation coefficient. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic value of serum Sirt-1 in the context of MASLD. RESULTS Serum Sirt-1 levels was significantly lower in the MASLD group (p < 0.001) and was inversely correlated with serum insulin (r = -0.163, p = 0.025), HOMA-IR (r = -0.169, p = 0.020) and triglyceride (r = -0.190, p = 0.009) and positively correlated with serum levels of high-density lipoprotein cholesterol (HDL-C) (r = 0.214, p = 0.003). The area under the curve (AUC) of Sirt-1 to predict the presence of MASLD was 0.76 (p < 0.001, 95% CI: 0.69, 0.82) with a sensitivity of 78.9, specificity of 61.1, positive predictive value (PPV) of 67.0%, and negative predictive value (NPV) of 74.0%. The optimal cutoff, determined using Youden's index, was 23.75 ng/mL. This indicates that serum Sirt-1 levels below 23.75 ng/mL may be indicative of MASLD. CONCLUSIONS The present study demonstrated that serum Sirt-1 levels were significantly lower in patients with MASLD. Furthermore, these levels were correlated with various metabolic parameters, including insulin resistance and the serum lipid profile. A serum Sirt-1 level below the cutoff of 23.75 ng/mL exhibited a significant association with the presence of MASLD, suggesting its potential utility in identifying patients with this condition.
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Affiliation(s)
- Farshad Amirkhizi
- Department of Nutrition, School of Public Health, Zabol University of Medical Sciences, Zabol, Iran
| | - Mahdiyeh Taghizadeh
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, No#44, Hojjatdoust St., Naderi St., Keshavarz Blvd, Tehran, 141556117, Iran
| | - Banafshe Khalese-Ranjbar
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, No#44, Hojjatdoust St., Naderi St., Keshavarz Blvd, Tehran, 141556117, Iran
| | - Soudabeh Hamedi-Shahraki
- Department of Epidemiology and Biostatistics, School of Public Health, Zabol University of Medical Sciences, Zabol, Iran
| | - Somayyeh Asghari
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, No#44, Hojjatdoust St., Naderi St., Keshavarz Blvd, Tehran, 141556117, Iran.
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Shang S, Yang H, Qu L, Fan D, Deng J. Ginsenoside, a potential natural product against liver diseases: a comprehensive review from molecular mechanisms to application. Crit Rev Food Sci Nutr 2025:1-25. [PMID: 39810734 DOI: 10.1080/10408398.2025.2451761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
Liver disease constitutes a significant cause of global mortality, with its pathogenesis being multifaceted. Identifying effective pharmacological and preventive strategies is imperative for liver protection. Ginsenosides, the major bioactive compounds found in ginseng, exhibit multiple pharmacological activities including protection against liver-related diseases by mitigating liver fat accumulation and inflammation, preventing hepatic fibrosis, and exerting anti-hepatocarcinogenic effects. However, a comprehensive overview elucidating the regulatory pathways associated with ginsenosides in liver disease remains elusive. This review aims to consolidate the molecular mechanisms through which different ginsenosides ameliorate distinct liver diseases, alongside the pathogenic factors underlying liver ailments. Notably, ginsenosides Rb1 and Rg1 demonstrate significantly effective in treating fatty liver, hepatitis, and liver fibrosis, and ginsenosides CK and Rh2 exhibit potent anti-hepatocellular carcinogenic effects. Their molecular mechanisms underlying these effects primarily involve the modulation of AMPK, NF-κB, TGF-β, NFR2, JNK, and other pathways, thereby attenuating hepatic fat accumulation, inflammation, inhibition of hepatic stellate cell activation, and promoting apoptosis in hepatocellular carcinoma cells. Furthermore, it provides insights into the safety profile and current applications of ginsenosides, thereby facilitating their clinical development. Consequently, ginsenosides present promising prospects for liver disease management, underscoring their potential as valuable therapeutic agents in this context.
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Affiliation(s)
- Shiyan Shang
- Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Biotech & Biomed Research Institute, School of Chemical Engineering, Northwest University, Xi'an, China
| | - Haixia Yang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Linlin Qu
- Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Biotech & Biomed Research Institute, School of Chemical Engineering, Northwest University, Xi'an, China
| | - Daidi Fan
- Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Biotech & Biomed Research Institute, School of Chemical Engineering, Northwest University, Xi'an, China
| | - Jianjun Deng
- Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Biotech & Biomed Research Institute, School of Chemical Engineering, Northwest University, Xi'an, China
- State Key Laboratory of Vegetable Biobreeding, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China
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Feng Y, Liu CH, Yang J, Zhang H, Li L, Yang Q, Gan W, Yang Z, Gong P, Fu C, Qian G, Li D. Integrative analysis of non12-hydroxylated bile acid revealed the suppressed molecular map of alternative pathway in nonalcoholic steatohepatitis mice. FASEB J 2024; 38:e70167. [PMID: 39556333 DOI: 10.1096/fj.202401630r] [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: 07/17/2024] [Revised: 10/17/2024] [Accepted: 10/28/2024] [Indexed: 11/19/2024]
Abstract
Bile acids (BAs) are significantly altered in the liver and serum of patients with nonalcoholic steatohepatitis (NASH). However, the underlying mechanisms of these changes, particularly BA alternative pathways (BAP) responsible for non12-OH BAs, remain unclear. RNA-seq data were initially analyzed to reveal the changes of gene expression in NASH patients. Targeted metabolomics were conducted on plasma from NASH mice induced by high-fat or western diet with CCl4 for 10-24 weeks. Liver tissues were examined using proteomics, RT-qPCR, and western blotting. An integrated approach was then employed to analyze protein interactions and network correlations. Analysis of RNA-seq data revealed the inhibition of CYP7B1 in NASH patients, indicating the dysregulation of BAP. In NASH mouse models, dysregulation of BA circulation was observed by increased plasma total BA (TBA) levels and decreased liver TBA, with liver swelling and histopathological changes. Targeted metabolomics revealed suppressed levels of non12-OH BAs, which inversely correlated with increased liver injury markers. The reduced mRNA and protein expression of Fxr and upregulation of Lxr signaling in livers suggested the suppressed BAP was modulated by Fxr-Lxr signaling. Moreover, BAP interactions predominantly implicated multiple metabolism disruptions, involving 7 hub proteins (Hk1, Acadsb, Pklr, Insr, Ldlr, Cyp27a1, and Cyp7b1), offering promising therapeutic targets for NASH. We presented the metabolic and proteomic map of BAP and its regulatory network in NASH progression. Therapeutic targeting of BAP or its co-regulatory proteins holds promise for NASH treatment and metabolic syndrome management.
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Affiliation(s)
- Yanruyu Feng
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
- Ninth People's Hospital of Zhengzhou, Zhengzhou, China
| | - Chang-Hai Liu
- Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Jingtao Yang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - He Zhang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Lian Li
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Qian Yang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Wei Gan
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Zi Yang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Puyang Gong
- College of Pharmacy, Southwest Minzu University, Chengdu, China
| | - Chunmei Fu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Guangsheng Qian
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Dapeng Li
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
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Farías C, Cisternas C, Caicedo A, Mercado L, Valenzuela R, Calderón H, Espinosa A, Videla LA, Muñoz LA. High-fiber basil seed flour reduces insulin resistance and hepatic steatosis in high-fat diet mice. NPJ Sci Food 2024; 8:90. [PMID: 39516211 PMCID: PMC11549410 DOI: 10.1038/s41538-024-00329-z] [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: 03/14/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024] Open
Abstract
The incidence of insulin resistance (IR) and hepatic steatosis is increasing, with dietary fiber playing a protective role against these disorders. Ocimum basilicum L., widely used in food, pharmaceutical, and cosmetic industries, but their health-promoting properties remain underexplored. This study evaluated the effects of a fiber-rich fraction of partially defatted basil seeds (BSF) on IR, hepatic steatosis, and polyunsaturated fatty acid and short-chain fatty acid (SCFA) profiles in high-fat diet (HFD)-fed C57BL/6 J male mice. Mice were assigned to four groups and fed either a control diet or HFD, supplemented with BSF or oat flour for 4 weeks. HFD induced IR, hepatic steatosis, proinflammatory state, and a significant decreased in SCFA production. In contrast, supplementation with BSF attenuated IR, steatosis, liver damage, oxidative stress, and inflammation, while increasing n-3 polyunsaturated fatty acids in liver, adipocytes, and erythrocytes, and enhancing SCFA production, suggesting potential therapeutic benefits in managing these conditions.
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Affiliation(s)
- Camila Farías
- Nutrition Department, Faculty of Medicine, University of Chile, Santiago, 8380000, Chile
| | - Camila Cisternas
- School of Health Care Sciences , Universidad San Sebastián, Puerto Montt, Chile
| | - Angie Caicedo
- School of Agronomy, Faculty of Agronomy and Food Sciences , Pontificia Universidad Católica de Valparaíso, Quillota, 2260000, Chile
| | - Lorena Mercado
- Nutrition Department, Faculty of Medicine, University of Chile, Santiago, 8380000, Chile
- Universidad Andrés Bello, Medicina, Facultad Medicina, 8370035, Santiago, Chile
| | - Rodrigo Valenzuela
- Nutrition Department, Faculty of Medicine, University of Chile, Santiago, 8380000, Chile
| | - Héctor Calderón
- Food Science Lab, Faculty of Medicine and Health Sciences, Universidad Central de Chile, Santiago, 8330546, Chile
| | - Alejandra Espinosa
- Center of Interdisciplinary Biomedical and Engineering Research for Health-MEDING. Universidad de Valparaíso, Valparaíso, Chile
- Medical Technology Department, Faculty of Medicine, University of Chile, Santiago, Chile
| | - L A Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Loreto A Muñoz
- Food Science Lab, Faculty of Medicine and Health Sciences, Universidad Central de Chile, Santiago, 8330546, Chile.
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8
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De Rosa L, Salvati A, Martini N, Chiappino D, Cappelli S, Mancini M, Demi L, Ghiadoni L, Bonino F, Brunetto MR, Faita F. An ultrasound multiparametric method to quantify liver fat using magnetic resonance as standard reference. Liver Int 2024; 44:3008-3019. [PMID: 39189634 DOI: 10.1111/liv.16078] [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: 04/03/2024] [Revised: 07/15/2024] [Accepted: 08/11/2024] [Indexed: 08/28/2024]
Abstract
BACKGROUND & AIMS There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference. METHODS Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis. RESULTS The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73). CONCLUSIONS Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC.
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Affiliation(s)
- Laura De Rosa
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
- Department of Information Engineering and Computer Science, University of Trento, Trento, Italy
| | | | | | | | - Simone Cappelli
- Department of Clinical and Experimental Medicine, Pisa University, Pisa, Italy
| | - Marcello Mancini
- Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy
| | - Libertario Demi
- Department of Information Engineering and Computer Science, University of Trento, Trento, Italy
| | - Lorenzo Ghiadoni
- Emergency Medicine Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
| | - Ferruccio Bonino
- Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy
| | - Maurizia R Brunetto
- Hepatology Unit, Pisa University Hospital, Pisa, Italy
- Department of Clinical and Experimental Medicine, Pisa University, Pisa, Italy
- Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy
| | - Francesco Faita
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
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9
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Daniel N, Genua F, Jenab M, Mayén AL, Chrysovalantou Chatziioannou A, Keski-Rahkonen P, Hughes DJ. The role of the gut microbiome in the development of hepatobiliary cancers. Hepatology 2024; 80:1252-1269. [PMID: 37055022 PMCID: PMC11487028 DOI: 10.1097/hep.0000000000000406] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 03/31/2023] [Accepted: 04/03/2023] [Indexed: 04/15/2023]
Abstract
Hepatobiliary cancers, including hepatocellular carcinoma and cancers of the biliary tract, share high mortality and rising incidence rates. They may also share several risk factors related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and rates of obesity. Recent data also suggest a role for the gut microbiome in the development of hepatobiliary cancer and other liver pathologies. The gut microbiome and the liver interact bidirectionally through the "gut-liver axis," which describes the interactive relationship between the gut, its microbiota, and the liver. Here, we review the gut-liver interactions within the context of hepatobiliary carcinogenesis by outlining the experimental and observational evidence for the roles of gut microbiome dysbiosis, reduced gut barrier function, and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to hepatobiliary cancer development. We also outline the latest findings regarding the impact of dietary and lifestyle factors on liver pathologies as mediated by the gut microbiome. Finally, we highlight some emerging gut microbiome editing techniques currently being investigated in the context of hepatobiliary diseases. Although much work remains to be done in determining the relationships between the gut microbiome and hepatobiliary cancers, emerging mechanistic insights are informing treatments, such as potential microbiota manipulation strategies and guiding public health advice on dietary/lifestyle patterns for the prevention of these lethal tumors.
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Affiliation(s)
- Neil Daniel
- Cancer Biology and Therapeutics Laboratory, Conway Institute, School of Biomedical and Biomolecular Sciences, University College Dublin, Dublin, Ireland
| | - Flavia Genua
- Cancer Biology and Therapeutics Laboratory, Conway Institute, School of Biomedical and Biomolecular Sciences, University College Dublin, Dublin, Ireland
| | - Mazda Jenab
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
| | - Ana-Lucia Mayén
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
| | | | - Pekka Keski-Rahkonen
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
| | - David J. Hughes
- Cancer Biology and Therapeutics Laboratory, Conway Institute, School of Biomedical and Biomolecular Sciences, University College Dublin, Dublin, Ireland
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Zhu J, Zhang M, Yue Y, Zhu J, Li D, Sun G, Chen X, Zhang H. Toxic Beauty: Parabens and benzophenone-type UV Filters linked to increased non-alcoholic fatty liver disease risk. CHEMOSPHERE 2024; 366:143555. [PMID: 39424158 DOI: 10.1016/j.chemosphere.2024.143555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 10/13/2024] [Accepted: 10/15/2024] [Indexed: 10/21/2024]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased concomitantly with heightened exposure to environmental chemicals, such as benzophenone-type ultraviolet (BP-type UV) filters and parabens, which are prevalent in personal care products. This study aimed to investigate the potential link between the exposure to these chemicals and the risk of developing NAFLD. We conducted a case-control study involving 228 participants from South China, encompassing individuals diagnosed with NAFLD and healthy controls. Blood samples were collected and analyzed for the presence of 11 parabens and 8 BP-type UV filters. The findings revealed significantly elevated concentrations of several parabens and BP-type UV filters in the blood of patients with NAFLD compared with the healthy cohort. Notably, methylparaben (MeP), ethylparaben (EtP), isopropylparaben (iPrP), butylparaben (BuP), isobutylparaben (iBuP), 3,4-dihydroxybenzoic acid (3,4-DHB), total parabens (Σparabens), BP1, BP3, BP4, and 4-hydroxybenzophenone (4-OH-BP) were identified as significant predictors of NAFLD prevalence. Through multiple regression analyses, the blood levels of iBuP, Σparabens, and BP4 were found to be significantly associated with elevated triglycerides (TG) (β = 0.59 mmol/L, 95% CI = 0.11-1.59), total bilirubin (TBIL) (β = 2.81 μmol/L, 95% CI = 0.46-15.6) or direct bilirubin (DBIL) (β = 1.89 μmol/L, 95% CI = 0.47-10.2), and reduced globulins (GLB) (β = -0.29 g/L, 95% CI = -0.07 to -5.45), respectively, which are indicators of liver damage. Moreover, TBIL and DBIL were found to mediate 26.7% and 24.6% of the increase in NAFLD prevalence associated with Σparabens, respectively. In conclusion, this study offers pioneering insights into human exposure to parabens and BP-type UV filters as well as their hepatotoxic potential.
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Affiliation(s)
- Jing Zhu
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, China
| | - Mingyue Zhang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, 510632, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, China
| | - Yuhan Yue
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, 510632, China
| | - Jinsen Zhu
- Department of Internal Medicine, Licheng Street Community Health Servic Center (Licheng hospital), Guangzhou, 511399, China
| | - Dehai Li
- Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Guodong Sun
- Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, 517000, China
| | - Xiaomei Chen
- Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China.
| | - Hua Zhang
- Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China.
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Deng J, Ji W, Liu H, Li L, Wang Z, Hu Y, Wang Y, Zhou Y. Development and validation of a machine learning-based framework for assessing metabolic-associated fatty liver disease risk. BMC Public Health 2024; 24:2545. [PMID: 39294603 PMCID: PMC11412026 DOI: 10.1186/s12889-024-19882-z] [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: 10/26/2023] [Accepted: 08/26/2024] [Indexed: 09/20/2024] Open
Abstract
BACKGROUND The existing predictive models for metabolic-associated fatty liver disease (MAFLD) possess certain limitations that render them unsuitable for extensive population-wide screening. This study is founded upon population health examination data and employs a comparison of eight distinct machine learning (ML) algorithms to construct the optimal screening model for identifying high-risk individuals with MAFLD in China. METHODS We collected physical examination data from 5,171,392 adults residing in the northwestern region of China, during the year 2021. Feature selection was conducted through the utilization of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Additionally, class balancing parameters were incorporated into the models, accompanied by hyperparameter tuning, to effectively address the challenges posed by imbalanced datasets. This study encompassed the development of both tree-based ML models (including Classification and Regression Trees, Random Forest, Adaptive Boosting, Light Gradient Boosting Machine, Extreme Gradient Boosting, and Categorical Boosting) and alternative ML models (specifically, k-Nearest Neighbors and Artificial Neural Network) for the purpose of identifying individuals with MAFLD. Furthermore, we visualized the importance scores of each feature on the selected model. RESULTS The average age (standard deviation) of the 5,171,392 participants was 51.12 (15.00) years, with 52.47% of the participants being females. MAFLD was diagnosed by specialized physicians. 20 variables were finally included for analyses after LASSO regression model. Following ten rounds of cross-validation and parameter optimization for each algorithm, the CatBoost algorithm exhibited the best performance, achieving an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.862. The ranking of feature importance indicates that age, BMI, triglyceride, fasting plasma glucose, waist circumference, occupation, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, systolic blood pressure, diastolic blood pressure, ethnicity and cardiovascular diseases are the top 13 crucial factors for MAFLD screening. CONCLUSION This study utilized a large-scale, multi-ethnic physical examination data from the northwestern region of China to establish a more accurate and effective MAFLD risk screening model, offering a new perspective for the prediction and prevention of MAFLD.
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Affiliation(s)
- Jiale Deng
- Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, Guangdong, China
| | - Weidong Ji
- Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, Guangdong, China
| | - Hongze Liu
- Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, Guangdong, China
| | - Lin Li
- Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, Guangdong, China
| | - Zhe Wang
- Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, Guangdong, China
| | - Yurong Hu
- School of Computer Science, China University of Geosciences, Wuhan, Beihe, 430074, China
| | - Yushan Wang
- People's Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Urumqi, 830054, Xinjiang, China.
| | - Yi Zhou
- Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, Guangdong, China.
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12
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Niu C, Zhang J, Khalid N, Zhu K, Syed T, Liu H, Okolo PI. Cardiovascular complications during delivery hospitalizations in patients with nonalcoholic fatty liver disease in pregnancy. Eur J Gastroenterol Hepatol 2024; 36:1141-1148. [PMID: 38874917 DOI: 10.1097/meg.0000000000002802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/15/2024]
Abstract
OBJECTIVE While the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and long-term cardiovascular risks has been studied, the impact of MASLD on cardiovascular events during delivery hospitalizations remains relatively unexplored. This study aims to examine the prevalence of cardiovascular diseases (CVDs) and cardiac arrhythmias in pregnant patients with MASLD and identify potential risk factors. METHODS A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted to assess maternal cardiovascular outcomes. Multivariable logistic regression models were employed, and adjusted odds ratios (AOR) were calculated to evaluate the association between MASLD and cardiovascular outcomes during pregnancy. RESULTS The study sample included 17 593 pregnancies with MASLD and 41 171 211 pregnancies without this condition. Women with MASLD exhibited an increased risk of congestive heart failure [AOR 3.45, 95% confidence interval (CI) 1.04-11.43], cardiac arrhythmia (AOR 2.60, 95% CI 1.94-3.49), and gestational hypertensive complications (AOR 3.30, 95% CI 2.93-3.72). Pregnancies with MASLD were also associated with a higher rate of pulmonary edema (AOR 3.30, 95% CI 1.60-6.81). CONCLUSION MASLD is an independent risk factor for cardiovascular complications during delivery hospitalizations, emphasizing the necessity for prepregnancy screening and targeted prevention strategies to manage CVD risks in expectant patients with MASLD.
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Affiliation(s)
- Chengu Niu
- Internal Medicine Department, Internal Medicine Residency Program, Rochester General Hospital, Rochester, New York
| | - Jing Zhang
- Psychiatry Department, Rainier Springs Behavioral Health Hospital, Vancouver, Washington
| | - Nida Khalid
- Division of Gastroenterology, Rochester General Hospital, Rochester, New York, USA
| | - Kaiwen Zhu
- Internal Medicine Department, Internal Medicine Residency Program, Rochester General Hospital, Rochester, New York
| | - Tausif Syed
- Division of Gastroenterology, Rochester General Hospital, Rochester, New York, USA
| | - Hongli Liu
- Internal Medicine Department, Internal Medicine Residency Program, Rochester General Hospital, Rochester, New York
| | - Patrick I Okolo
- Division of Gastroenterology, Rochester General Hospital, Rochester, New York, USA
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Green V, Lin J, McGrath M, Lloyd A, Ma P, Higa K, Roytman M. FIB-4 Reliability in Patients With Severe Obesity: Lower Cutoffs Needed? J Clin Gastroenterol 2024; 58:825-829. [PMID: 37983815 DOI: 10.1097/mcg.0000000000001937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 10/02/2023] [Indexed: 11/22/2023]
Abstract
BACKGROUND Liver biopsy is the gold standard to evaluate hepatic fibrosis; however, it has many drawbacks, especially in patients with severe obesity. Noninvasive testing such as the FIB-4 score is increasingly being used as the initial screening tool to identify patients at risk for advanced fibrosis. The broader applicability of FIB-4 and the precision of its cutoff values remain uncertain in metabolic dysfunction-associated steatotic liver disease and patients with severe obesity. Our study explored the correlation between FIB-4 scores and intraoperative liver biopsy in patients with severe obesity undergoing bariatric surgery. METHODS A total of 632 patients with severe obesity underwent preoperative vibration-controlled transient elastography and intraoperative liver biopsy during bariatric surgery from January 2020 to August 2021. Variables collected included patient demographics, laboratory values, abdominal ultrasound, vibration-controlled transient elastography, and liver biopsy results. ANOVA 1-way test, χ 2 tests, and Fisher exact tests were used for quantitative and qualitative variables, respectively. The 95% CIs for the mean FIB-4 scores were used to generate surrogate cutoff values. The proposed FIB-4 cutoffs for F0-1, F2, F3, and F4 were 0.62 (CI: 0.59, 0.64), 0.88 (0.74, 1.01), 1.24 (0.94, 1.54), and 1.53 (0.82, 2.24), respectively. Area under the curve (AUC) methods were used to compare traditional to proposed cutoff values. RESULTS Applying the traditional FIB-4 cutoffs to approximate advanced fibrosis yielded an AUC of 0.5748. Use of the proposed FIB-4 cutoffs increased the AUC to 0.6899. The proposed FIB-4 cutoffs correctly identified 40 patients with biopsy-proven advanced fibrosis (F3-F4), all of which would have been missed using traditional cutoffs. CONCLUSION Our study revealed that the use of the currently accepted FIB-4 cutoffs as the screening modality for identifying patients with advanced fibrosis due to metabolic dysfunction-associated steatotic liver disease is insufficient and will result in missing patients with histologically confirmed advanced fibrosis. Use of the revised FIB-4 scores should be considered to diagnose patients with severe obesity at high risk of liver disease progression.
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Affiliation(s)
| | | | - Morgan McGrath
- Community Regional Medical Center, Fresno Heart & Surgical Hospital, Fresno, CA
| | - Aaron Lloyd
- Community Regional Medical Center, Fresno Heart & Surgical Hospital, Fresno, CA
| | - Pearl Ma
- Community Regional Medical Center, Fresno Heart & Surgical Hospital, Fresno, CA
| | - Kelvin Higa
- Community Regional Medical Center, Fresno Heart & Surgical Hospital, Fresno, CA
| | - Marina Roytman
- Gastroenterology and Hepatology, University of California, San Francisco
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Alam N, Jia L, Cheng A, Ren H, Fu Y, Ding X, Haq IU, Liu E. Global research trends on gut microbiota and metabolic dysfunction-associated steatohepatitis: Insights from bibliometric and scientometric analysis. Front Pharmacol 2024; 15:1390483. [PMID: 39070791 PMCID: PMC11273336 DOI: 10.3389/fphar.2024.1390483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 06/24/2024] [Indexed: 07/30/2024] Open
Abstract
Background Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory subtype of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed as a replacement term for NAFLD, a common, multifactorial and poorly understood liver disease whose incidence is increasing worldwide. In recent years, there has been increasing scientific interest in exploring the relationship between gut microbiota and MASH. To learn more about the gut microbiota in MASH, this study aims to provide a comprehensive analysis of the knowledge structure and research hotspots from a bibliometric perspective. Methods We searched the Web of Science Core Collection for articles and reviews that covered the connections between gut microbiota and MASH over the last decade. The Online Analysis Platforms, VOSviewer, CiteSpace, the R tool "bibliometrix" were used to analyzed existing publications trends and hotspots. Results A total of 4,069 documents related to the interaction between gut microbiota and MASH were retrieved from 2014 to 2023. The number of annual publications increased significantly over the last decade, particularly in the United States and China. The University of California-San Diego was the most productive institution, while researcher Rohit Loomba published the most papers in the field. Younossi ZM was ranked as the first co-cited author and largest contributor of highly cited articles in the field. Gastroenterology and hepatology were the most common specialty category. The most cited journal in the last decade was Hepatology. The Keyword Bursts analysis highlighted the importance of studying the association between gut microbiota and MASH, as well as related factors such as metabolic syndrome, insulin resistance, endotoxemia and overgrowth of gut bacteria. Keyword clusters with co-citation were used to illustrate important topics including intestinal permeability, insulin sensitivity and liver immunology. The most common keywords include insulin resistance, obesity, dysbiosis, inflammation and oxidative stress, which are current hotspots. Conclusion Our analysis highlights key aspects of this field and emphasizes multiorgan crosstalk in MASLD/MASH pathogenesis. In particular, the central role of the gut-liver axis and the significant influence of gut microbiota dysbiosis on disease progression are highlighted. Furthermore, our results highlight the transformative potential of microbiota-specific therapies and cover the way for innovative healthcare and pharmaceutical strategies.
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Affiliation(s)
- Naqash Alam
- Laboratory Animal Center, School of Basic Medical Sciences, Health Science Center, Xi’an Jiaotong University, Xi’an, China
| | - Linying Jia
- Laboratory Animal Center, School of Basic Medical Sciences, Health Science Center, Xi’an Jiaotong University, Xi’an, China
| | - Ao Cheng
- Laboratory Animal Center, School of Basic Medical Sciences, Health Science Center, Xi’an Jiaotong University, Xi’an, China
| | - Honghao Ren
- Laboratory Animal Center, School of Basic Medical Sciences, Health Science Center, Xi’an Jiaotong University, Xi’an, China
| | - Yu Fu
- Laboratory Animal Center, School of Basic Medical Sciences, Health Science Center, Xi’an Jiaotong University, Xi’an, China
| | - Xinhua Ding
- Laboratory Animal Center, School of Basic Medical Sciences, Health Science Center, Xi’an Jiaotong University, Xi’an, China
| | - Ihtisham Ul Haq
- Department of Neurobiology, School of Basic Medical Sciences, Health Science Center, Xi’an Jiaotong University, Xi’an, China
| | - Enqi Liu
- Laboratory Animal Center, School of Basic Medical Sciences, Health Science Center, Xi’an Jiaotong University, Xi’an, China
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15
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Matsumoto K, Ohsugi Y, Tayama C, Hayashi M, Kato Y, Ohashi M, Chiba M. Serum miR‑29 is increased in mice with early liver fibrosis. Exp Ther Med 2024; 28:285. [PMID: 38800048 PMCID: PMC11117116 DOI: 10.3892/etm.2024.12573] [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: 11/17/2023] [Accepted: 04/17/2024] [Indexed: 05/29/2024] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is a fatty liver disease that is not caused by alcohol consumption and is characterized by fatty degeneration, inflammation and hepatocellular damage. Therefore, predicting future fibrosis is critical in the early stages of NASH to prevent disease progression. The present study examined histological changes in the liver as well as microRNA (miR/miRNA) expression changes in the liver and serum of NASH mice model to identify potential biomarker candidates that could predict early fibrosis. This study used 6-week-old C57BL/6NJcl male mice and fed the control with a standard solid diet (CE-2) for breeding and propagation and NASH groups with a high-fat diet [choline-deficient high-fat and 0.1% (w/v) methionine supplemented diet], respectively. Agilent Technologies miRNA microarray was used to investigate microRNA expression in the liver and serum. Hematoxylin and eosin staining of the livers of the NASH group mice during the second week of feeding revealed fatty degeneration, balloon-like degeneration and inflammatory cell infiltration, confirming that the mice were in a state of NASH. The livers of the NASH group mice at 6 weeks of feeding showed fibrosis. Microarray analysis revealed that miRNAs were upregulated and 47 miRNAs were downregulated in the liver of the NASH group. Pathway analysis using OmicsNet predicted miR-29 to target collagen genes. Furthermore, miR-29 was downregulated in the livers of NASH-induced mice but upregulated in serum. These findings suggested that lower miR-29 expression in NASH-induced liver would increase collagen expression and fibrosis. Early liver fibrosis suggests that miR-29 leaks from the liver into the bloodstream, and elevated serum miR-29 levels may be a predictive biomarker for early liver fibrosis.
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Affiliation(s)
- Kana Matsumoto
- Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
| | - Yuhei Ohsugi
- Department of Medical Technology, School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
| | - Chisa Tayama
- Department of Medical Technology, School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
| | - Momone Hayashi
- Department of Medical Technology, School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
| | - Yumiko Kato
- Department of Medical Technology, School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
| | - Mizuho Ohashi
- Department of Medical Technology, School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
| | - Mitsuru Chiba
- Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
- Research Center for Biomedical Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan
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Bansal SK, Bansal MB. Pathogenesis of MASLD and MASH - role of insulin resistance and lipotoxicity. Aliment Pharmacol Ther 2024; 59 Suppl 1:S10-S22. [PMID: 38451123 DOI: 10.1111/apt.17930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 12/26/2023] [Accepted: 02/20/2024] [Indexed: 03/08/2024]
Abstract
BACKGROUND Insulin resistance and lipotoxicity are extremely interconnected but fundamental in setting the stage for the development of MASLD/MASH. AIM/METHODS A comprehensive literature search was performed and key themes were synthesised to provide insight into the underlying molecular mechanisms of insulin resistance and lipotoxicity in the liver, muscle, pancreas and adipose tissue and how organ cross-talk is fundamental to driving disease pathogenesis. RESULTS Classical thinking postulates that excess FFA load exceeds the storage capacity of adipose tissue, which is predicated upon both genetic and environmental factors. This results in insulin resistance and compensatory hyperinsulinaemia by pancreatic beta cells to overcome target organ insulin resistance. As adipocyte dysfunction worsens, not only are excess FFA delivered to other organs, including skeletal muscle, pancreas and liver but a pro-inflammatory milieu is established with increases in IL-6, TNF-α and changes in adipokine levels (increased leptin and decreased adiponectin). With increased intramuscular lipid accumulation, lipotoxic species decrease insulin signalling, reduce glucose uptake by downregulation of GLUT4 and decrease glycogen synthesis. With this additional reduced capacity, hyperglycaemia is further exacerbated and increased FFA are delivered to the liver. The liver has the largest capacity to oxidise fat and to adapt to these stressors and, therefore, has become the last line of defence for excess lipid storage and utilisation, the capacity of which may be impacted by genetic and environmental factors. However, when the liver can no longer keep up with increasing FFA delivery and DNL, lipotoxic species accumulate with ensuing mitochondrial dysfunction, increased ER stress, oxidant stress and inflammasome activation, all of which drive hepatocyte injury and apoptosis. The resulting wound healing response, marked by stellate cell activation, drives collagen accumulation, progressive fibrosis, and, ultimately, end organ failure and death. This vicious cycle and complex interplay between insulin resistance, hyperinsulinaemia, lipotoxicity and multi-directional cross-talk among different target organs are critical drivers of MASLD/MASH. CONCLUSIONS Targeting tissue-specific insulin resistance and hyperinsulinaemia while decreasing FFA load (lipotoxicity) through dietary and lifestyle changes remain the best upstream interventions.
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Affiliation(s)
- Shalini K Bansal
- Sidney Kimmel College of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Meena B Bansal
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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17
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Zheng D, Liu X, Zeng W, Zhou W, Zhou C. Association of hepatic steatosis and liver fibrosis with chronic obstructive pulmonary disease among adults. Sci Rep 2024; 14:10822. [PMID: 38734742 PMCID: PMC11088642 DOI: 10.1038/s41598-024-61696-x] [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: 07/18/2023] [Accepted: 05/08/2024] [Indexed: 05/13/2024] Open
Abstract
With high prevalence and substantial mortality, metabolic dysfunction-associated steatotic liver disease and chronic obstructive pulmonary disease (COPD) are significant public health concerns. Utilizing a large, population-based dataset from the National Health and Nutrition Examination Survey, our study probes the relationship between COPD prevalence and hepatic steatosis and fibrosis, as measured by Vibration-Controlled Transient Elastography. We analyzed data from 693 individuals with COPD and 7229 without. Through weighted multivariate logistic regression analysis, a restricted cubic spline curve, and threshold effect analysis, we investigated the correlation between the severity of hepatic steatosis and fibrosis and the presence of COPD. Our findings revealed a positive correlation between the controlled attenuation parameter (CAP) and COPD prevalence [OR = 1.03 (95% CI 1.01, 1.05)], even after multivariate adjustment. Furthermore, we observed a U-shaped association between CAP and COPD, where the inflection point, CAP value of 264.85 dB/m, corresponded to the lowest COPD prevalence. Our study emphasizes a substantial and complex link between hepatic steatosis and COPD. These findings urge healthcare professionals to factor liver health into COPD management and prompt further exploration into the underlying mechanisms. This could pave the way for the development of improved prevention and treatment strategies.
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Affiliation(s)
- Dayang Zheng
- Department of Thoracic Surgery, East Hospital, The Second Affiliated Hospital, Hengyang Medical School, University of South China, No. 30 Jiefang Road, Shigu District, Hengyang, 421009, Hunan Province, China
| | - Xiang Liu
- Department of Thoracic Surgery, East Hospital, The Second Affiliated Hospital, Hengyang Medical School, University of South China, No. 30 Jiefang Road, Shigu District, Hengyang, 421009, Hunan Province, China
| | - Wei Zeng
- Department of Thoracic Surgery, East Hospital, The Second Affiliated Hospital, Hengyang Medical School, University of South China, No. 30 Jiefang Road, Shigu District, Hengyang, 421009, Hunan Province, China
| | - Wangyan Zhou
- Department of Medical Record, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Chunxiang Zhou
- Department of Thoracic Surgery, East Hospital, The Second Affiliated Hospital, Hengyang Medical School, University of South China, No. 30 Jiefang Road, Shigu District, Hengyang, 421009, Hunan Province, China.
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18
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Moriyama K. Prediction and Validation of Metabolic Dysfunction-Associated Fatty Liver Disease Using Fatty Liver-Related Indices in a Japanese Population. Metab Syndr Relat Disord 2024; 22:190-198. [PMID: 38153394 DOI: 10.1089/met.2023.0212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2023] Open
Abstract
Background: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. It is uncertain how indices that predict fatty liver are associated with MAFLD in Japanese. Methods: Among subjects who underwent a health examination at our hospital, 1257 (men: 787, women: 474) subjects participated in fatty liver evaluation of the fatty liver index (FLI) and fatty liver predicting index (FLPI) were included in this cross-sectional study. The discriminatory ability of each index for MAFLD was tested using receiver operating characteristic curve analysis. The association between FLI, FLPI, and MAFLD was investigated using multiple logistic regression analysis. Results: FLI and FLPI had good discriminatory ability for identifying MAFLD in both men and women, with specific cutoff values. Both FLI and FLPI were significantly higher in subjects with MAFLD, and the odds of MAFLD were higher among those in the highest tertile relative to the lowest tertile in both men and women. FLI and FLPI were higher in subjects who met the criteria for both MAFLD and metabolic syndrome (MetS) compared to those who had MAFLD or MetS alone, and most of the examined parameters in subjects with both conditions indicated a high metabolic risk profile. Conclusions: The study suggests that FLI and FLPI are valuable tools for predicting MAFLD and are similarly correlated with the disease. Furthermore, the highest values of these indices were observed in subjects who met the criteria for both MAFLD and MetS, emphasizing the importance of considering both conditions when assessing metabolic risk.
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Affiliation(s)
- Kengo Moriyama
- Department of Clinical Health Science, Tokai University School of Medicine, Tokai University Hachioji Hospital, Tokyo, Japan
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19
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Chondrogianni ME, Kyrou I, Androutsakos T, Flessa CM, Menenakos E, Chatha KK, Aranan Y, Papavassiliou AG, Kassi E, Randeva HS. Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe. Front Endocrinol (Lausanne) 2024; 15:1344376. [PMID: 38524631 PMCID: PMC10957571 DOI: 10.3389/fendo.2024.1344376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 01/05/2024] [Indexed: 03/26/2024] Open
Abstract
Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD.
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Affiliation(s)
- Maria Eleni Chondrogianni
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Endocrine Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Kyrou
- Laboratory of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, Athens, Greece
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Centre for Health & Life Sciences, Coventry University, Coventry, United Kingdom
- Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham, United Kingdom
- College of Health, Psychology and Social Care, University of Derby, Derby, United Kingdom
| | - Theodoros Androutsakos
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Christina-Maria Flessa
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Menenakos
- 5th Surgical Clinic, Department of Surgery, ‘Evgenidion Hospital’, National and Kapodistrian University of Athens Medical School, Athens, Greece
| | - Kamaljit Kaur Chatha
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Department of Biochemistry and Immunology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
| | - Yekaterina Aranan
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
| | - Athanasios G. Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Eva Kassi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Endocrine Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Harpal S. Randeva
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Centre for Health & Life Sciences, Coventry University, Coventry, United Kingdom
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20
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Hwang SJ, Choi YJ, Wang JH, Son CG. Lactobacillus Casei-fermented Amomum Xanthioides Mitigates non-alcoholic fatty liver disease in a high-fat diet mice model. Biomed Pharmacother 2024; 172:116250. [PMID: 38320334 DOI: 10.1016/j.biopha.2024.116250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/30/2024] [Accepted: 02/01/2024] [Indexed: 02/08/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a substantial global health issue owing to its high prevalence and the lack of effective therapies. Fermentation of medicinal herbs has always been considered a feasible strategy for enhancing efficacy in treating various ailments. This study aimed to investigate the potential benefits of the Lactobacillus casei-fermented Amomum xanthioides (LAX) on NAFLD in a high-fat diet model. HFD-fed C57BL6/j mice were administered with 200 mg/kg of LAX or unfermented Amomum xanthioides (AX) or 100 mg/kg of metformin for 6 weeks from the 4th week. The 10-week HFD-induced alterations of hepatic lipid accumulation and hepatic inflammation were significantly attenuated by LAX dominantly (more than AX or metformin), which evidenced by pathohistological findings, lipid contents, inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 6 and IL-1β, oxidative parameters such as reactive oxygen species (ROS) and malondialdehyde (MDA), and molecular changes reversely between lipogenic proteins such as glycerol-3-phosphate acyltransferase (GPAM) and sterol regulatory element-binding protein (SREBP)- 1, and lipolytic proteins including peroxisome proliferator-activated receptor (PPAR-α) and AMP-activated kinase (AMPK)-α in the liver tissues. In addition, the abnormal serum lipid parameters (triglyceride, total cholesterol and LDL-cholesterol) notably ameliorated by LAX. In conclusion, these findings support the potential of LAX as a promising plant-derived remedy for NAFLD.
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Affiliation(s)
- Seung-Ju Hwang
- Institute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedukdae-ro 176 bun-gil, Seo-gu, Daejeon 35235, the Republic of Korea; Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 75, Daedukdae-ro 176 bun-gil, Seo-gu, Daejeon 35235, the Republic of Korea
| | - Yu-Jin Choi
- Institute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedukdae-ro 176 bun-gil, Seo-gu, Daejeon 35235, the Republic of Korea; Department of Internal Medicine, College of Korean Medicine, Se-Myung University, Semyeong-ro 65, Jecheon-si, Chungcheongbuk-do, 27136, the Republic of Korea
| | - Jing-Hua Wang
- Institute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedukdae-ro 176 bun-gil, Seo-gu, Daejeon 35235, the Republic of Korea; Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 75, Daedukdae-ro 176 bun-gil, Seo-gu, Daejeon 35235, the Republic of Korea.
| | - Chang-Gue Son
- Institute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedukdae-ro 176 bun-gil, Seo-gu, Daejeon 35235, the Republic of Korea; Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 75, Daedukdae-ro 176 bun-gil, Seo-gu, Daejeon 35235, the Republic of Korea.
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21
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Wang W, Cheng X, Yao J, Xue H, Li C, Wang X, Zhang Y, Chen S, Zhang Y. What Do Higher Alanine Aminotransferase Levels Mean in Premature Ovarian Insufficiency? Reprod Sci 2024; 31:469-479. [PMID: 37723330 DOI: 10.1007/s43032-023-01303-y] [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: 12/27/2022] [Accepted: 07/10/2023] [Indexed: 09/20/2023]
Abstract
The objective of this study was to investigate the relationship between alanine aminotransferase and related biochemical parameters and potential risk factors in women with premature ovarian insufficiency (POI). This is a retrospective cohort study with 126 POI patients (including subclinical POI, n= 27) and 130 healthy controls who visited our clinic between April 2021 to November 2022. Associations were investigated by multiple linear regression, Person correlation analysis, the Kruskal-Wallis test, Mann-Whitney U test, and the independent t-test. When compared to controls, analysis of POI patients showed that body mass index (BMI), uric acid (UA) and urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), monocyte/lymphocyte ratio, monocyte count (MONO), neutrophil count (NEUT), follicle-stimulating hormone (FSH), luteinizing hormone, and neutrophil/lymphocyte ratio (NLR) were significantly higher, while estradiol (E2), the lymphocyte count and the AST/ALT ratio were lower (P < 0.05). According to linear correlation, it was clear that BMI, FSH, white blood cell count (WBC), NEUT, MONO, UA, AST, and NLR were positively associated with ALT (r = 0.215, 0.388, 0.195, 0.187, 0.184, 0.605, 0.819, and 0.189, respectively, all P < 0.05) while E2 was negatively associated with ALT (r = -0.278, P < 0.05). In addition, multiple linear regression revealed a significant, independent, and positive correlation between AST, FSH, and ALT (B =1.403 and 0.069, respectively, P < 0.05). Analysis revealed that the levels of ALT were significantly higher in POI patients. In addition, BMI, FSH, UA, AST, MONO, NLR, NEUT, and WBC were positively associated with ALT in POI patients. E2 was negatively associated with ALT. Multiple linear regression revealed an independent and positive correlation between AST, FSH, and ALT. In addition, there was also a risk of liver function damage in women with POI and subclinical POI. If patients were diagnosed with POI, early examination and corresponding intervention will be required to effectively prevent the further development of liver disease.
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Affiliation(s)
- Weina Wang
- Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, No. 20 Xi-Si Road, Nantong, 226001, Jiangsu, China
- Medical School of Nantong University, Nantong, China
| | - Xi Cheng
- Medical School of Nantong University, Nantong, China
| | - Jinhan Yao
- Medical School of Nantong University, Nantong, China
| | - Hanchun Xue
- Medical School of Nantong University, Nantong, China
| | - Chenglu Li
- Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, No. 20 Xi-Si Road, Nantong, 226001, Jiangsu, China
- Medical School of Nantong University, Nantong, China
| | - Xia Wang
- Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, No. 20 Xi-Si Road, Nantong, 226001, Jiangsu, China
| | - You Zhang
- Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, No. 20 Xi-Si Road, Nantong, 226001, Jiangsu, China
- Medical School of Nantong University, Nantong, China
| | - Siyi Chen
- Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, No. 20 Xi-Si Road, Nantong, 226001, Jiangsu, China
- Medical School of Nantong University, Nantong, China
| | - Yuquan Zhang
- Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, No. 20 Xi-Si Road, Nantong, 226001, Jiangsu, China.
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22
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Apostolo D, Ferreira LL, Vincenzi F, Vercellino N, Minisini R, Latini F, Ferrari B, Burlone ME, Pirisi M, Bellan M. From MASH to HCC: the role of Gas6/TAM receptors. Front Immunol 2024; 15:1332818. [PMID: 38298195 PMCID: PMC10827955 DOI: 10.3389/fimmu.2024.1332818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 01/02/2024] [Indexed: 02/02/2024] Open
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is the replacement term for what used to be called nonalcoholic steatohepatitis (NASH). It is characterized by inflammation and injury of the liver in the presence of cardiometabolic risk factors and may eventually result in the development of hepatocellular carcinoma (HCC), the most common form of primary liver cancer. Several pathogenic mechanisms are involved in the transition from MASH to HCC, encompassing metabolic injury, inflammation, immune dysregulation and fibrosis. In this context, Gas6 (Growth Arrest-Specific 6) and TAM (Tyro3, Axl, and MerTK) receptors may play important roles. The Gas6/TAM family is involved in the modulation of inflammation, lipid metabolism, fibrosis, tumor progression and metastasis, processes which play an important role in the pathophysiology of acute and chronic liver diseases. In this review, we discuss MASH-associated HCC and the potential involvement of the Gas6/TAM system in disease development and progression. In addition, since therapeutic strategies for MASH and HCC are limited, we also speculate regarding possible future treatments involving the targeting of Gas6 or TAM receptors.
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Affiliation(s)
- Daria Apostolo
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Luciana L. Ferreira
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Federica Vincenzi
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Nicole Vercellino
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Rosalba Minisini
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Federico Latini
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Barbara Ferrari
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
| | - Michela E. Burlone
- Department of Internal Medicine, Azienda Ospedaliero-Universitaria Maggiore Della Carità, Novara, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
- Department of Internal Medicine, Azienda Ospedaliero-Universitaria Maggiore Della Carità, Novara, Italy
- Center on Autoimmune and Allergic Diseases, Università del Piemonte Orientale, Novara, Italy
| | - Mattia Bellan
- Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy
- Department of Internal Medicine, Azienda Ospedaliero-Universitaria Maggiore Della Carità, Novara, Italy
- Center on Autoimmune and Allergic Diseases, Università del Piemonte Orientale, Novara, Italy
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23
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Gao SS, Shen YL, Chen YW, Wei XZ, Hu JJ, Wang J, Wu WJ. Liver Metabolomics Analysis Revealing Key Metabolites Associated with Different Stages of Nonalcoholic Fatty Liver Disease in Hamsters. Comb Chem High Throughput Screen 2024; 27:1303-1317. [PMID: 37859316 DOI: 10.2174/0113862073238503230924180432] [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: 02/28/2023] [Revised: 07/10/2023] [Accepted: 08/10/2023] [Indexed: 10/21/2023]
Abstract
BACKGROUND AND AIM Nonalcoholic fatty liver disease (NAFLD) is not only the top cause of liver diseases but also a hepatic-correlated metabolic syndrome. This study performed untargeted metabolomics analysis of NAFLD hamsters to identify the key metabolites to discriminate different stages of NAFLD. METHODS Hamsters were fed a high-fat diet (HFD) to establish the NAFLD model with different stages (six weeks named as the NAFLD1 group and twelve weeks as the NAFLD2 group, respectively). Those liver samples were analyzed by untargeted metabolomics (UM) analysis to investigate metabolic changes and metabolites to discriminate different stages of NAFLD. RESULTS The significant liver weight gain in NAFLD hamsters was observed, accompanied by significantly increased levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Moreover, the levels of TG, LDL-C, ALT, and AST were significantly higher in the NAFLD2 group than in the NAFLD1 group. The UM analysis also revealed the metabolic changes; 27 differently expressed metabolites were detected between the NAFLD2 and NAFLD1 groups. More importantly, the levels of N-methylalanine, allantoin, glucose, and glutamylvaline were found to be significantly different between any two groups (control, NAFLD2 and NAFLD1). Receiver operating characteristic curve (ROC) curve results also showed that these four metabolites are able to distinguish control, NAFLD1 and NAFLD2 groups. CONCLUSION This study indicated that the process of NAFLD in hamsters is accompanied by different metabolite changes, and these key differently expressed metabolites may be valuable diagnostic biomarkers and responses to therapeutic interventions.
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Affiliation(s)
- Shan-Shan Gao
- Department of Ultrasound, Ningbo No. 2 Hospital, University of Chinese Academy of Sciences, Ningbo Zhejiang, 315000, China
| | - Yue-Liang Shen
- Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou Zhejiang, 310011, China
| | - Yun-Wen Chen
- Department of Ultrasound, Ningbo No. 2 Hospital, University of Chinese Academy of Sciences, Ningbo Zhejiang, 315000, China
| | - Xiu-Zhi Wei
- Department of Ultrasound, Ningbo No. 2 Hospital, University of Chinese Academy of Sciences, Ningbo Zhejiang, 315000, China
| | - Jing-Jing Hu
- Department of Ultrasound, Ningbo No. 2 Hospital, University of Chinese Academy of Sciences, Ningbo Zhejiang, 315000, China
| | - Jue Wang
- Department of Ultrasound, Ningbo No. 2 Hospital, University of Chinese Academy of Sciences, Ningbo Zhejiang, 315000, China
| | - Wen-Jing Wu
- Department of Ultrasound, Ningbo No. 2 Hospital, University of Chinese Academy of Sciences, Ningbo Zhejiang, 315000, China
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24
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Raya-Cano E, Molina-Luque R, Vaquero-Abellán M, Molina-Recio G, Jiménez-Mérida R, Romero-Saldaña M. Metabolic syndrome and transaminases: systematic review and meta-analysis. Diabetol Metab Syndr 2023; 15:220. [PMID: 37899468 PMCID: PMC10614379 DOI: 10.1186/s13098-023-01200-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 10/24/2023] [Indexed: 10/31/2023] Open
Abstract
BACKGROUND Metabolic syndrome (MetS) is a group of metabolic abnormalities characterised by hypertension, central obesity, dyslipidaemia and dysregulation of blood glucose, associated with the risk of diabetes, cardiovascular disease and overall mortality. The presence of elevated liver enzymes may precede the development of MetS, with alterations of the liver being observed that are directly related to metabolic problems. The study aims to provide the best evidence on the association between liver enzymes (ALT, AST, GGT) and MetS by determining the effect size of these biomarkers. METHODS A systematic review and meta-analysis of studies indexed in PubMed and Scopus databases were performed. Study quality was assessed using the STROBE tool. The Grade Pro tool was used to evaluate the evidence, and the quantitative synthesis was performed using RevMan (Cochrane Collaboration). RESULTS Seventeen articles comparing liver enzyme concentrations between 76,686 with MetS (MetS+) and 201,855 without MetS (MetS-) subjects were included. The concentration of ALT, AST and GGT in the MetS + subjects was significantly higher than in the control group 7.13 IU/L (CI95% 5.73-8.54; p < 0.00001; I2 = 96%), 2.68 IU/L (CI95% 1.82-3.54; p < 0.00001; I2 = 96%) and 11.20 IU/L (CI95% 7.11-15.29; p < 0.00001; I2 = 96%), respectively. CONCLUSIONS The evaluation of the relationship of liver enzymes in the pathophysiological process of MetS could lead to new insights into early diagnosis.
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Affiliation(s)
- Elena Raya-Cano
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain
| | - Rafael Molina-Luque
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain.
- Lifestyles, Innovation and Health (GA-16), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain.
| | - Manuel Vaquero-Abellán
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain
| | - Guillermo Molina-Recio
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain
- Lifestyles, Innovation and Health (GA-16), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain
| | - Rocío Jiménez-Mérida
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain
| | - Manuel Romero-Saldaña
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain
- Lifestyles, Innovation and Health (GA-16), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain
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25
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Barroso LN, Salarini J, Leite NC, Villela-Nogueira CA, Dávalos A, Carmo MDGT, Ferreira Peres WA. Effect of fish oil supplementation on the concentration of miRNA-122, FGF-21 and liver fibrosis in patients with NAFLD: Study protocol for a randomized, double-blind and placebo-controlled clinical trial. Clin Nutr ESPEN 2023; 57:117-125. [PMID: 37739645 DOI: 10.1016/j.clnesp.2023.06.027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 06/22/2023] [Accepted: 06/25/2023] [Indexed: 09/24/2023]
Abstract
BACKGROUND & AIMS To date, no specific drugs are available for non-alcoholic fatty liver disease (NAFLD), though the effect of fish oil supplementation on improving fibrosis in patients with NAFLD has been evaluated. N-3 polyunsaturated fatty acids (n-3 PUFA) may modulate the concentration of microRNAs (miRNAs) and fibroblast growth factor (FGF)-21, which have been identified as non-invasive markers of liver fibrosis. The present study aims to evaluate whether n-3 PUFA supplementation can modulate miRNA-122 and FGF-21 and improve liver fibrosis and steatosis, measured by transient hepatic elastography (THE), in individuals with NAFLD. METHODS A randomized, double-blind, placebo-controlled clinical trial will be conducted to evaluate the effect of 4 g/day supplementation of fish oil (2100 mg EPA and 924 mg DHA) in patients with NAFLD over a 6-month period. Fifty-two patients aged >19 years will be randomly assigned to either a placebo (olive oil) or treatment (fish oil) group. Anthropometric data, food intake, physical activity, body composition, resting energy expenditure (evaluated using indirect calorimetry), liver enzymes, platelets, lipids and glucose profile, inflammatory markers (such as C-reactive protein, neutrophil/lymphocyte, platelet/lymphocyte, and monocyte/lymphocyte ratios), miRNA-122 and FGF-21 concentration, and incorporation of fatty acids into the erythrocyte membrane (analyzed using gas chromatography) as well as the degree of liver fibrosis and steatosis assessed using THE (Fibroscan® Touch 502, Paris, France) and liver biomarkers Steato-Brazilian Longitudinal Study of Adult Health, Fatty Liver Index, NAFLD Fibrosis Score, Fibrosis-4 score, and FibroScan-AST score will be evaluated at the beginning and end of the treatment. Continuous variables with normal distribution will be compared between placebo and intervention groups using Student's T test for independent samples; continuous non-parametric variables will be compared using Dunn or Mann-Whitney test. Associations between categorical variables will be analyzed using the chi-square test, and within-group differences will be evaluated using the Wilcoxon signed-ranks test. The criterion for determining significance will be set at 5%. CONCLUSION The present study protocol will investigate the supplementation of EPA-rich fish oil as an alternative treatment for NAFLD and its feasibility in affecting the concentration of miRNA-122 and FGF-21 markers. Its findings will offer valuable contributions to the literature. REGISTRATION ReBEC number RBR-8dp876.
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Affiliation(s)
- Lygia N Barroso
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil; School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Jessica Salarini
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil; School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Nathalie Carvalho Leite
- School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Cristiane A Villela-Nogueira
- School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Alberto Dávalos
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA), Madrid, Spain
| | - Maria das Graças Tavares Carmo
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil
| | - Wilza Arantes Ferreira Peres
- Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil.
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Syed-Abdul MM. Expanding Pharmacists' Role in the Management of Non-Alcoholic Fatty Liver Disease. PHARMACY 2023; 11:151. [PMID: 37736923 PMCID: PMC10514885 DOI: 10.3390/pharmacy11050151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/28/2023] [Accepted: 09/20/2023] [Indexed: 09/23/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) stands as an increasingly pressing global health challenge, underscoring the need for timely identification to facilitate effective treatment and prevent the progression of chronic liver disorders. Given the projected scarcity of specialized healthcare professionals, particularly hepatologists and gastroenterologists, the role of pharmacists emerges as pivotal in NAFLD management. This article sheds light on the potential of pharmacists within community pharmacy settings, not as diagnostic entities, but as facilitators in recognizing and screening individuals at elevated NAFLD risk using validated non-invasive tools like portable devices and calculators. By prioritizing patient education, referrals, and continuous monitoring, pharmacists can refine NAFLD management, ultimately advancing patient outcomes. Enhancing pharmacists' impact in early NAFLD detection and management can be facilitated through collaborations with healthcare institutions and the incorporation of patient self-assessment tools. This collaborative approach holds promise for further promoting improved liver health within the community.
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Affiliation(s)
- Majid Mufaqam Syed-Abdul
- Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada
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Gou X, Qin L, Wu D, Xie J, Lu Y, Zhang Q, He Y. Research Progress of Takeda G Protein-Coupled Receptor 5 in Metabolic Syndrome. Molecules 2023; 28:5870. [PMID: 37570840 PMCID: PMC10421342 DOI: 10.3390/molecules28155870] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 07/28/2023] [Accepted: 08/01/2023] [Indexed: 08/13/2023] Open
Abstract
Bile acids are acknowledged as signaling molecules involved in metabolic syndrome. The Takeda G protein-coupled receptor 5 (TGR5) functions as a significant bile acid receptor. The accumulated evidence suggests that TGR5 involves lipid homeostasis, glucose metabolism, and inflammation regulation. In line with this, recent preclinical studies also demonstrate that TGR5 plays a significant role in the generation and progression of metabolic syndrome, encompassing type 2 diabetes mellitus, obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). In this review, we discuss the role of TGR5 in metabolic syndrome, illustrating the underlying mechanisms and therapeutic targets.
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Affiliation(s)
- Xianmei Gou
- Guizhou Engineering Research Center of Industrial Key-Technology for Dendrobium Nobile, Zunyi Medical University, Zunyi 563000, China
| | - Lin Qin
- Guizhou Engineering Research Center of Industrial Key-Technology for Dendrobium Nobile, Zunyi Medical University, Zunyi 563000, China
| | - Di Wu
- Guizhou Engineering Research Center of Industrial Key-Technology for Dendrobium Nobile, Zunyi Medical University, Zunyi 563000, China
| | - Jian Xie
- Guizhou Engineering Research Center of Industrial Key-Technology for Dendrobium Nobile, Zunyi Medical University, Zunyi 563000, China
| | - Yanliu Lu
- Guizhou Engineering Research Center of Industrial Key-Technology for Dendrobium Nobile, Zunyi Medical University, Zunyi 563000, China
- Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China
| | - Qianru Zhang
- Guizhou Engineering Research Center of Industrial Key-Technology for Dendrobium Nobile, Zunyi Medical University, Zunyi 563000, China
| | - Yuqi He
- Guizhou Engineering Research Center of Industrial Key-Technology for Dendrobium Nobile, Zunyi Medical University, Zunyi 563000, China
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Lee J, Kim H, Kang YW, Kim Y, Park MY, Song JH, Jo Y, Dao T, Ryu D, Lee J, Oh CM, Park S. LY6D is crucial for lipid accumulation and inflammation in nonalcoholic fatty liver disease. Exp Mol Med 2023; 55:1479-1491. [PMID: 37394588 PMCID: PMC10394021 DOI: 10.1038/s12276-023-01033-w] [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: 01/08/2023] [Revised: 02/07/2023] [Accepted: 04/17/2023] [Indexed: 07/04/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a serious metabolic disorder characterized by excess fat accumulation in the liver. Over the past decade, NAFLD prevalence and incidence have risen globally. There are currently no effective licensed drugs for its treatment. Thus, further study is required to identify new targets for NAFLD prevention and treatment. In this study, we fed C57BL6/J mice one of three diets, a standard chow diet, high-sucrose diet, or high-fat diet, and then characterized them. The mice fed a high-sucrose diet had more severely compacted macrovesicular and microvesicular lipid droplets than those in the other groups. Mouse liver transcriptome analysis identified lymphocyte antigen 6 family member D (Ly6d) as a key regulator of hepatic steatosis and the inflammatory response. Data from the Genotype-Tissue Expression project database showed that individuals with high liver Ly6d expression had more severe NAFLD histology than those with low liver Ly6d expression. In AML12 mouse hepatocytes, Ly6d overexpression increased lipid accumulation, while Ly6d knockdown decreased lipid accumulation. Inhibition of Ly6d ameliorated hepatic steatosis in a diet-induced NAFLD mouse model. Western blot analysis showed that Ly6d phosphorylated and activated ATP citrate lyase, which is a key enzyme in de novo lipogenesis. In addition, RNA- and ATAC-sequencing analyses revealed that Ly6d drives NAFLD progression by causing genetic and epigenetic changes. In conclusion, Ly6d is responsible for the regulation of lipid metabolism, and inhibiting Ly6d can prevent diet-induced steatosis in the liver. These findings highlight Ly6d as a novel therapeutic target for NAFLD.
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Affiliation(s)
- Jibeom Lee
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
| | - Hyeonhui Kim
- Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea
| | - Yun-Won Kang
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
| | - Yumin Kim
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
| | - Moon-Young Park
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
| | - Ji-Hong Song
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
| | - Yunju Jo
- Department of Molecular Cell Biology, Sungkyunkwan University (SKKU) School of Medicine, Suwon, Korea
| | - Tam Dao
- Department of Molecular Cell Biology, Sungkyunkwan University (SKKU) School of Medicine, Suwon, Korea
| | - Dongryeol Ryu
- Department of Molecular Cell Biology, Sungkyunkwan University (SKKU) School of Medicine, Suwon, Korea
| | - Junguee Lee
- Department of Pathology, St Mary's Hospital, the Catholic University of Korea, Daejeon, Korea
| | - Chang-Myung Oh
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea.
| | - Sangkyu Park
- Department of Precision Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
- Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do, Korea.
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Park MJ, Kim H, Kim MG, Kim K. Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: A network meta-analysis. Clin Mol Hepatol 2023; 29:693-704. [PMID: 36907574 PMCID: PMC10366812 DOI: 10.3350/cmh.2022.0330] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 01/25/2023] [Accepted: 03/06/2023] [Indexed: 03/14/2023] Open
Abstract
BACKGROUND/AIMS Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP-1RA) and thiazolidinedione (TZD) can improve nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). However, comprehensive research comparing the effects of GLP-1RA and TZD is limited. Thus, this study aimed to compare the effects of GLP-1RA and TZD on NAFLD or NASH through a network meta-analysis. METHODS The PubMed, Embase, Web of Science, and Scopus databases were searched for randomized controlled trials (RCTs) that explored the efficacy of GLP-1RAs or TZDs in adult patients with NAFLD or NASH. The outcomes were liver biopsy-based (NAFLD activity score [NAS], fibrosis stage, and NASH resolution), noninvasive technique-based (liver fat content on proton magnetic resonance spectroscopy [1H-MRS] and controlled attenuation parameter [CAP]), biological, and anthropometric indicators. A random effects model was used to calculate the mean difference (MD) and relative risk with 95% confidence interval (CI). RESULTS Twenty-five RCTs with 2,237 overweight or obese patients were included. GLP-1RA was significantly superior in reducing liver fat content evaluated using 1H-MRS (MD -2.42, 95% CI -3.84 to -1.00), body mass index (MD -1.60, 95% CI -2.41 to -0.80), and waist circumference (MD -4.89, 95% CI -8.17 to -1.61) than TZD. In liver biopsy-based evaluation and liver fat content assessment using CAP, GLP-1RA tended to surpass TZD, albeit not significantly. Sensitivity analysis showed consistent results with the main results. CONCLUSION Compared with TZD, GLP-1RA had better effects on liver fat content, body mass index, and waist circumference in overweight or obese patients with NAFLD or NASH.
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Affiliation(s)
- Min Jeong Park
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hayeon Kim
- College of Pharmacy, Korea University, Sejong, Korea
| | - Myeong Gyu Kim
- College of Pharmacy, Ewha Womans University, Seoul, Korea
| | - Kyungim Kim
- College of Pharmacy, Korea University, Sejong, Korea
- Institute of Pharmaceutical Science, Korea University, Sejong, Korea
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Sun L, Li N, Zhang L, Chen J. The Role of ElastPQ in Assessing Liver Stiffness for Non-Alcoholic Fatty Liver Disease in Patients Treated with Atypical Antipsychotic Drugs. Neuropsychiatr Dis Treat 2023; 19:1491-1502. [PMID: 37408709 PMCID: PMC10319346 DOI: 10.2147/ndt.s409210] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 06/14/2023] [Indexed: 07/07/2023] Open
Abstract
Objective To evaluate the role of elastography point quantification (ElastPQ) for the quantitative assessment of stiffness in the fatty liver disease in mental disorder patients and to provide a noninvasive detection method for non-alcoholic fatty liver (NAFLD) caused by atypical antipsychotics drugs (AAPDs). Methods A total number of 168 mental disorder patients treated with AAPDs and 58 healthy volunteers were enrolled in this study. All the subjects underwent ultrasound and ElastPQ tests. The basic data of the patients were analyzed. Results BMI, liver function, and the value of ElastPQ were considerably higher in the patient group than that in the healthy volunteers. The values of liver stiffness obtained by ElastPQ were increased gradually from 3.48(3.14-3.81) kPa in the normal liver to 8.15(6.44-9.88) in the severe fatty liver. The receiver operating characteristic (ROC) for the diagnosis of fatty liver with ElastPQ were 0.85, 0.79, 0.80, and 0.87 for the diagnosis of normal, mild, moderate, and severe steatosis, respectively, with a sensitive/specificity of 79%/76.4%, 85.7%/78.3%, 86.2%/73%, and 81.3%/82.1%, correspondingly. Moreover, ElastPQ in the olanzapine group was higher than those in the risperidone and aripiprazole groups (5.11(3.83-5.61) kPa vs 4.35(3.63-4.98) kPa, P < 0.05; 5.11(3.83-5.61) kPa vs 4.79(4.18-5.24) kPa, P < 0.05). After one-year treatment, the value of ElastPQ was 4.43(3.85-5.22) kPa, but it was 5.81(5.09-7.33) kPa in patients treated for more than three years. This value increased with treatment prolongation (P < 0.05). Conclusion ElastPQ is a real-time, quantitative method for assessing the stiffness of NAFLD. The liver stiffness value could be varied in the different stages of fatty liver. Olanzapine has a considerable influence on liver stiffness. The long-term use of AAPDs can increase the stiffness value of fatty liver.
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Affiliation(s)
- Linlin Sun
- Department of Ultrasound, Peking University Huilonguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People’s Republic of China
| | - Nan Li
- Department of Ultrasound, Peking University Huilonguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People’s Republic of China
| | - Ligang Zhang
- Department of Psychiatry, Peking University Huilonguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People’s Republic of China
| | - Jingxu Chen
- Department of Psychiatry, Peking University Huilonguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People’s Republic of China
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Chakraborty R, Sharma D, Kapoor DU, Dwivedi A, Khabiya R, Sen S. Implications of metabolic dysfunction associated fatty liver disease in COVID-19. World J Clin Cases 2023; 11:1275-1286. [PMID: 36926128 PMCID: PMC10013103 DOI: 10.12998/wjcc.v11.i6.1275] [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: 11/02/2022] [Revised: 12/20/2022] [Accepted: 01/31/2023] [Indexed: 02/24/2023] Open
Abstract
Metabolic associated fatty liver disorder (MAFLD) characterizes the contributing etiologies (i.e., type 2 diabetes mellitus, metabolic syndrome, overweight) of individuals with fatty liver disease that affects 1/3rd of the world population. In 2020, the coronavirus disease 2019 (COVID-19) crisis was unprecedented, and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2. MAFLD patients are frequently obese with added metabolic menace like diabetes, hypertension, and dyslipidemia leading to greater jeopardy of COVID-19. MAFLD patients are 4 to 6-fold more prone towards infections. COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin. Hence, MAFLD in COVID-19 patients worsens the condition significantly. The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission. Direct hepatic injury, enhanced levels of inflammatory cytokines, declined hepatic mitochondrial activity, and compromised immunity are considered as some underlying mechanisms. The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients. The review systematically analyzes the effect of striking two worldwide pandemics (MAFLD and COVID-19) together in the present era.
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Affiliation(s)
- Raja Chakraborty
- Institute of Pharmacy, Assam Don Bosco University, Guwahati 782402, Assam, India
| | - Deepak Sharma
- School of Medical Sciences, Adamas University, Kolkata 700126, West Bengal, India
| | - Devesh U Kapoor
- Department of Pharmacy, Dr. Dayaram Patel Pharmacy College, Bardoli 394601, Gujarat, India
| | - Akanksha Dwivedi
- Department of Pharmacy, Acropolis Institute of Pharmaceutical Education & Research, Indore 453771, Madhya Pradesh, India
| | - Rakhi Khabiya
- Department of Pharmacy, Acropolis Institute of Pharmaceutical Education & Research, Indore 453771, Madhya Pradesh, India
| | - Saikat Sen
- Faculty of Pharmaceutical Science, Assam down town University, Guwahati 781026, Assam, India
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Nam K, Torkzaban M, Halegoua-DeMarzio D, Wessner CE, Lyshchik A. Improving diagnostic accuracy of ultrasound texture features in detecting and quantifying hepatic steatosis using various beamforming sound speeds. Phys Med Biol 2023; 68:10.1088/1361-6560/acb635. [PMID: 36696691 PMCID: PMC10009771 DOI: 10.1088/1361-6560/acb635] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 01/25/2023] [Indexed: 01/26/2023]
Abstract
Objective.While ultrasound image texture has been utilized to detect and quantify hepatic steatosis, the texture features extracted using a single (conventionally 1540 m s-1) beamforming speed of sound (SoS) failed to achieve reliable diagnostic performance. This study aimed to investigate if the texture features extracted using various beamforming SoSs can improve the accuracy of hepatic steatosis detection and quantification.Approach.Patients with suspected non-alcoholic fatty liver disease underwent liver biopsy or MRI proton density fat fraction (PDFF) as part of standard of care, were prospectively enrolled. The radio-frequency data from subjects' right and left liver lobes were collected using 6 beamforming SoSs: 1300, 1350, 1400, 1450, 1500 and 1540 m s-1and analyzed offline. The texture features, i.e. Contrast, Correlation, Energy and Homogeneity from gray-level co-occurrence matrix of normalized envelope were obtained from a region of interest in the liver parenchyma.Main results.Forty-three subjects (67.2%) were diagnosed with steatosis while 21 had no steatosis. Homogeneity showed the area under the curve (AUC) of 0.75-0.82 and 0.58-0.81 for left and right lobes, respectively with varying beamforming SoSs. The combined Homogeneity value over 1300-1540 m s-1from left and right lobes showed the AUC of 0.90 and 0.81, respectively. Furthermore, the combined Homogeneity values from left and right lobes over 1300-1540 m s-1improved the AUC to 0.94. The correlation between texture features and steatosis severity was improved by using the images from various beamforming SoSs. The combined Contrast values over 1300-1540 m s-1from left and right lobes demonstrated the highest correlation (r= 0.90) with the MRI PDFF while the combined Homogeneity values over 1300-1540 m s-1from left and right lobes showed the highest correlation with the biopsy grades (r= -0.81).Significance.The diagnostic accuracy of ultrasound texture features in detecting and quantifying hepatic steatosis was improved by combining its values extracted using various beamforming SoSs.
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Affiliation(s)
- Kibo Nam
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Mehnoosh Torkzaban
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Dina Halegoua-DeMarzio
- Department of Medicine, Division of Gastroenterology & Hepatology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Corinne E. Wessner
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Andrej Lyshchik
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
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Mardi P, Kargar R, Fazeli R, Qorbani M. Allium sativum: A potential natural compound for NAFLD prevention and treatment. Front Nutr 2023; 10:1059106. [PMID: 36819702 PMCID: PMC9931905 DOI: 10.3389/fnut.2023.1059106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 01/09/2023] [Indexed: 02/05/2023] Open
Abstract
Introduction Non-alcoholic fatty liver disease (NAFLD) results from an excessive accumulation of fat particles that causes liver inflammation, which ultimately causes liver damage. There is still considerable uncertainty about the effects of any nutritional supplements compared to no additional intervention. This review aimed to evaluate the efficacy of Allium sativum (A. sativum), known as garlic, in preventing and treating NAFLD. Methods A systematic search based on a search strategy consisting of two components of "NAFLD" and "Allium sativum" in databases including PubMed, Web of Science (WoS), and SCOPUS was conducted on papers evaluating the effects of A. sativum on NAFLD treatment and prevention. We obtained studies from inception until 20 September 2022, followed by study selection and data extraction based on our eligibility criteria. Consequently, qualitative and quantitative synthesis was conducted. Results Our qualitative analysis reveals that A. sativum consumption is linked to the prevention of NAFLD, especially in males, although qualitative data in this study regarding the therapeutic properties of NAFLD was controversial. Our meta-analysis showed that NAFLD patients treated with A. sativum have significantly declined aminotransferase levels. That is to say, our meta-analysis revealed a lower alanine transaminase (ALT) (SMD = -0.580, 95%CI = -0.822 to -0.338), and aspartate transaminase (AST(SMD = -0.526, 95%CI = -0.767 to -0.284) in NAFLD patients treated with A. sativum compared to the placebo group. Also, pooling data from case-control studies showed that A. sativum consumption decreases the odds of being diagnosed with NAFLD by 46% (OR = 0.538, 95%CI = 0.451-0.625). Conclusion A. sativum consumption is not merely associated with NAFLD prevention but also results in a considerable decline in blood aminotransferase levels in patients diagnosed with NAFLD. To put it simply, A. sativum is linked to a decline in AST and ALT, which are considered reliable biomarkers of NAFLD response to treatment. Nevertheless, A. sativum is insufficient to improve NAFLD independent of other dietary amendments and lifestyle modifications.
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Affiliation(s)
- Parham Mardi
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Reza Kargar
- Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
| | - Ramina Fazeli
- Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
| | - Mostafa Qorbani
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran,Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran,*Correspondence: Mostafa Qorbani,
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Sharma V, Sharma S, Akarshit, Kumar R, Sharma P, Mittal A, Kumar R, Sharma M. Effect of curcumin and zingiberone on non alcoholic fatty liver disease (NAFLD). AIP CONFERENCE PROCEEDINGS 2023; 2804:020254. [DOI: 10.1063/5.0162870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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CSAD Ameliorates Lipid Accumulation in High-Fat Diet-Fed Mice. Int J Mol Sci 2022; 23:ijms232415931. [PMID: 36555571 PMCID: PMC9783087 DOI: 10.3390/ijms232415931] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/06/2022] [Accepted: 12/07/2022] [Indexed: 12/23/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic disease manifested in hepatic steatosis, inflammation, fibrosis, etc., which affects over one-quarter of the population around the world. Since no effective therapeutic drugs are available to cope with this widespread epidemic, the functional research of genes with altered expression during NAFLD helps understand the pathogenesis of this disease and the development of new potential therapeutic targets for drugs. In the current work, we discovered via the analysis of the Gene Expression Omnibus (GEO) dataset that cysteine sulfinic acid decarboxylase (CSAD) decreased significantly in NAFLD patients, which was also confirmed in multiple NAFLD mouse models (HFD-fed C57BL/6J, db/db and HFHFrHC-fed C57BL/6J mice). Next, CSAD's function in the progression of NAFLD was explored using AAV-mediated liver-directed gene overexpression in an HFD-fed mouse model, where the overexpression of CSAD in the liver could alleviate NAFLD-associated pathologies, including body weight, liver/body weight ratio, hepatic triglyceride and total cholesterol, and the degree of steatosis. Mechanically, we found that the overexpression of CSAD could increase the expression of some genes related to fatty acid β-oxidation (Acad1, Ppara, and Acox1). Furthermore, we also detected that CSAD could improve mitochondrial injury in vitro and in vivo. Finally, we proposed that the effect of CSAD on lipid accumulation might be independent of the taurine pathway. In conclusion, we demonstrated that CSAD is involved in the development of NAFLD as a protective factor, which suggested that CSAD has the potential to become a new target for drug discovery in NAFLD.
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Liu ZS, Li PL, Ku YW, Chen PW. Oral Administration of Recombinant Lactoferrin-Expressing Probiotics Ameliorates Diet-Induced Lipid Accumulation and Inflammation in Non-Alcoholic Fatty Liver Disease in Mice. Microorganisms 2022; 10:2215. [PMID: 36363807 PMCID: PMC9694622 DOI: 10.3390/microorganisms10112215] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 11/04/2022] [Accepted: 11/07/2022] [Indexed: 07/22/2023] Open
Abstract
We have recently developed probiotics that can express bovine, human, or porcine lactoferrin (LF), and the present study evaluated the effect of these probiotics in improving non-alcoholic fatty liver disease (NAFLD). Three kinds of probiotic supplements, including lactic acid bacteria (LAB), LAB/LF, and inactivated LAB/LF, were prepared. The LAB supplement was prepared from 10 viable LAB without recombinant LF-expression, the LAB/LF supplement was prepared from 10 viable probiotics expressing LF, and the inactivated LAB/LF supplement was prepared from 10 inactivated probiotics expressing LF. A model of obese/NAFLD mice induced by a high-fat diet was established, and the mice were randomly divided into four groups and fed with a placebo, LAB, LAB/LF, or inactivated LAB daily for four weeks via oral gavage. The body weight, food intake, organ weight, biochemistry, and hepatic histopathological alterations and severity scoring were measured. The results revealed that the obese mice fed with any one of the three probiotic mixtures prepared from recombinant probiotics for four weeks exhibited considerably improved hepatic steatosis. These findings confirmed the assumption that specific probiotic strains or LF supplements could help to control NAFLD, as suggested in previous reports. Our data also suggest that the probiotics and LFs in probiotic mixtures contribute differently to improving the efficacy against NAFLD, and the expressed LF content in probiotics may help to boost their efficacy in comparison with the original probiotic mixtures. Moreover, when these LF-expressing probiotics were further inactivated by sonication, they displayed better efficacies than the viable probiotics against NAFLD. This study has provided intriguing data supporting the potential of recombinant probiotics in improving hepatic steatosis.
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Affiliation(s)
- Zhen-Shu Liu
- Department of Safety, Health and Environmental Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan
- Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi 61363, Taiwan
| | - Pei-Lin Li
- Department of Veterinary Medicine, National Chung Hsing University, Taichung 40249, Taiwan
| | - Yu-We Ku
- Department of Veterinary Medicine, National Chung Hsing University, Taichung 40249, Taiwan
- Animal and Plant Disease Control Center Yilan County, Wujie Township, Yilan County 268015, Taiwan
| | - Po-Wen Chen
- Department of Veterinary Medicine, National Chung Hsing University, Taichung 40249, Taiwan
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da Cruz NS, Pasquarelli-do-Nascimento G, e Oliveira ACP, Magalhães KG. Inflammasome-Mediated Cytokines: A Key Connection between Obesity-Associated NASH and Liver Cancer Progression. Biomedicines 2022; 10:2344. [PMID: 36289606 PMCID: PMC9598450 DOI: 10.3390/biomedicines10102344] [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: 09/06/2022] [Accepted: 09/18/2022] [Indexed: 11/18/2022] Open
Abstract
Liver cancer is one of the most lethal malignancies and is commonly diagnosed as hepatocellular carcinoma (HCC), a tumor type that affects about 90% of patients. Non-alcoholic steatohepatitis (NASH) and obesity are both risk factors for this disease. HCC initiation and progression are deeply linked with changes in the hepatic microenvironment, with cytokines playing key roles. The understanding of the pathogenic pathways that connect these disorders to liver cancer remains poor. However, the inflammasome-mediated cytokines associated with both diseases are central actors in liver cancer progression. The release of the pro-inflammatory cytokines IL-1β and IL-18 during inflammasome activation leads to several detrimental effects on the liver microenvironment. Considering the critical crosstalk between obesity, NASH, and HCC, this review will present the connections of IL-1β and IL-18 from obesity-associated NASH with HCC and will discuss approaches to using these cytokines as therapeutic targets against HCC.
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Affiliation(s)
| | | | | | - Kelly Grace Magalhães
- Laboratory of Immunology and Inflammation, Department of Cell Biology, University of Brasilia, Brasilia 70910-900, Brazil
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Insight into Potential Interactions of Thyroid Hormones, Sex Hormones and Their Stimulating Hormones in the Development of Non-Alcoholic Fatty Liver Disease. Metabolites 2022; 12:metabo12080718. [PMID: 36005590 PMCID: PMC9414490 DOI: 10.3390/metabo12080718] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 07/30/2022] [Accepted: 07/31/2022] [Indexed: 02/01/2023] Open
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common manifestation of metabolic syndrome. In addition to lifestyle, endocrine hormones play a role in the dysregulation of hepatic metabolism. The most common endocrine hormones contributing to metabolic syndrome are alterations in the levels of thyroid hormones (THs, predominantly in subclinical hypothyroidism) and of sex hormones (in menopause). These hormonal changes influence hepatic lipid and glucose metabolism and may increase hepatic fat accumulation. This review compares the effects of sex hormones, THs and the respective stimulating hormones, Thyroid-Stimulating Hormone (TSH) and Follicle-Stimulating Hormone (FSH), on the development of hepatosteatosis. TSH and FSH may be more relevant to the dysregulation of hepatic metabolism than the peripheral hormones because metabolic changes were identified when only levels of the stimulating hormones were abnormal and the peripheral hormones were still in the reference range. Increased TSH and FSH levels appear to have additive effects on the development of NAFLD and to act independently from each other.
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Trifan A, Stratina E, Nastasa R, Rotaru A, Stafie R, Zenovia S, Huiban L, Sfarti C, Cojocariu C, Cuciureanu T, Muzica C, Chiriac S, Girleanu I, Singeap AM, Stanciu C. Simultaneously Screening for Liver Steatosis and Fibrosis in Romanian Type 2 Diabetes Mellitus Patients Using Vibration-Controlled Transient Elastography with Controlled Attenuation Parameter. Diagnostics (Basel) 2022; 12:diagnostics12071753. [PMID: 35885657 PMCID: PMC9322355 DOI: 10.3390/diagnostics12071753] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 06/27/2022] [Accepted: 07/18/2022] [Indexed: 12/19/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common finding among patients with type 2 diabetes mellitus (T2DM). Between NAFLD and T2DM exist a bidirectional relationship. Patients with T2DM are at high risk for NAFLD, and evidence suggests that T2DM is linked to progressive NAFLD and poor liver outcomes. NAFLD promotes the development of T2DM and leads to a substantial increase in the risk of T2DM complications. This study aimed to assess the prevalence of liver steatosis and fibrosis in patients with T2DM from north-eastern Romania by using Vibration-Controlled Transient Elastography (VCTE) with Controlled Attenuation Parameter (CAP), which is a non-invasive method and can assess simultaneously liver steatosis and fibrosis. In total, 424 consecutive patients with T2DM were enrolled and evaluated using VCTE with CAP from January 2020 to January 2022. Clinical and laboratory data were recorded in all patients. For the CAP score, we used the following cut-offs: mild steatosis (S1)—274 dB/m, moderate steatosis (S2)—290 dB/m, and severe steatosis (S3)—302 dB/m. For liver fibrosis, to differentiate between fibrosis stages, the cut-off values were F ≥ 8.2 kPa for significant fibrosis (F2), F ≥ 9.7 kPa for advanced fibrosis (F3), and F ≥ 13.6 kPa for cirrhosis (F4). In total, 380 diabetic patients (72.6%) had liver steatosis (51.3% females, the mean age of 55.22 ± 10.88 years, mean body mass index (BMI) 29.12 ± 5.64 kg/m2). Among them, 26 (8.4%) patients had moderate liver steatosis (S2) and 242 (78.5%) patients had severe hepatic steatosis (S3). According to VCTE measurements, 176 (57.14%) patients had liver fibrosis, 36 (11.7%) of them had advanced fibrosis (F3), and 42 (13.6%) diabetic patients had cirrhosis (F4). Univariate analyses showed that severe steatosis was significantly associated with ferritin (β = 0.223, p = 0.022), total cholesterol (β = 0.159, p = 0.031), and HDL-cholesterol (β = −0.120, p = 0.006). In multivariate analyses, BMI (β = 0.349, p < 0.001), fasting plasma glucose (β = 0.211, p = 0.006), and triglycerides (β = 0.132, p = 0.044) were predictors of S3. Patients with T2DM have a high prevalence of severe steatosis and advanced fibrosis which can lead to the development and progression of complications with high morbidity and mortality rates. Hence, it is necessary to implement screening strategies to prevent advanced liver disease in patients with T2DM.
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Affiliation(s)
- Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
- Correspondence: (E.S.); (R.N.)
| | - Robert Nastasa
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
- Correspondence: (E.S.); (R.N.)
| | - Adrian Rotaru
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, 700111 Iasi, Romania
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Lanzaro F, Guarino S, D'Addio E, Salvatori A, D'Anna JA, Marzuillo P, Miraglia del Giudice E, Di Sessa A. Metabolic-associated fatty liver disease from childhood to adulthood: State of art and future directions. World J Hepatol 2022; 14:1087-1098. [PMID: 35978659 PMCID: PMC9258256 DOI: 10.4254/wjh.v14.i6.1087] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/26/2021] [Accepted: 04/25/2022] [Indexed: 02/06/2023] Open
Abstract
In 2020, an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease (MAFLD). This recent proposal reflects the close association of fatty liver with metabolic derangements, as demonstrated by previous robust data. Several factors [including genetics, inflammation, metabolic abnormalities, insulin resistance (IR), obesity, prenatal determinants, and gut–liver axis] have been found to be involved in MAFLD pathophysiology, but this tangled puzzle remains to be clearly understood. In particular, IR has been recognized as a key player in metabolic impairments development in children with fatty liver. On this ground, MAFLD definition focuses on the pathophysiological basis of the disease, by emphasizing the crucial role of metabolic impairments in this condition. Although primarily developed for adults, MAFLD diagnostic criteria have been recently updated with an age-appropriate definition for sex and age percentiles, because of the increasing attention to cardiometabolic risk in childhood. To date, accumulating evidence is available on the feasibility of MAFLD definition in clinical practice, but some data are still conflicting in highly selected populations. Considering the growing prevalence worldwide of fatty liver and its close relationship with metabolic dysfunction both in children and adults with subsequent increased cardiovascular risk, early strategies for MAFLD identification, treatment and prevention are needed. Novel therapeutic insights for MAFLD based on promising innovative biological techniques are also emerging. We aimed to summarize the most recent evidence in this intriguing research area both in children and adults.
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Affiliation(s)
- Francesca Lanzaro
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Elisabetta D'Addio
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Alessandra Salvatori
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Josè Alberto D'Anna
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
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NAFLD: Mechanisms, Treatments, and Biomarkers. Biomolecules 2022; 12:biom12060824. [PMID: 35740949 PMCID: PMC9221336 DOI: 10.3390/biom12060824] [Citation(s) in RCA: 183] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is one of the most common causes of liver diseases worldwide. NAFLD is growing in parallel with the obesity epidemic. No pharmacological treatment is available to treat NAFLD, specifically. The reason might be that NAFLD is a multi-factorial disease with an incomplete understanding of the mechanisms involved, an absence of accurate and inexpensive imaging tools, and lack of adequate non-invasive biomarkers. NAFLD consists of the accumulation of excess lipids in the liver, causing lipotoxicity that might progress to metabolic-associated steatohepatitis (NASH), liver fibrosis, and hepatocellular carcinoma. The mechanisms for the pathogenesis of NAFLD, current interventions in the management of the disease, and the role of sirtuins as potential targets for treatment are discussed here. In addition, the current diagnostic tools, and the role of non-coding RNAs as emerging diagnostic biomarkers are summarized. The availability of non-invasive biomarkers, and accurate and inexpensive non-invasive diagnosis tools are crucial in the detection of the early signs in the progression of NAFLD. This will expedite clinical trials and the validation of the emerging therapeutic treatments.
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Moayedfard Z, Sani F, Alizadeh A, Bagheri Lankarani K, Zarei M, Azarpira N. The role of the immune system in the pathogenesis of NAFLD and potential therapeutic impacts of mesenchymal stem cell-derived extracellular vesicles. Stem Cell Res Ther 2022; 13:242. [PMID: 35672797 PMCID: PMC9175371 DOI: 10.1186/s13287-022-02929-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 05/23/2022] [Indexed: 12/15/2022] Open
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by intra-hepatocyte triglyceride accumulation and concomitant involvement of the immune system with subsequent histological changes, tissue damage, and clinical findings. There are various molecular pathways involved in the progression of NAFLD including lipotoxicity, endoplasmic reticulum stress, and the immune response. Both innate and adaptive immune systems are involved in the NAFLD pathogenesis, and crosstalk between the immune cells and liver cells participates in its initiation and progression. Among the various treatments for this disease, new cell based therapies have been proposed. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC) (MSC-EVs) are new cell-free vehicles with low immunogenicity, which can suppress detrimental immune responses in inflamed tissues. This review aimed to express the immune system's molecular pathways associated with the initiation and progression of NAFLD. Then, the possible role of MSC-EVs in the treatment of this entity through immune response modulation was discussed. Finally, engineered EVs enhanced by specific therapeutic miRNA were suggested for alleviating the pathological cellular events in liver disease.
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Affiliation(s)
- Zahra Moayedfard
- Department of Tissue Engineering and Cell Therapy, School of Advanced Technologies in Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farnaz Sani
- Hematology and Cell Therapy Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Aliakbar Alizadeh
- Department of Tissue Engineering and Cell Therapy, School of Advanced Technologies in Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Mohammad Zarei
- Renal Division, Brigham and Woman's Hospital, Harvard Medical School, Boston, MA, USA
- John B. Little Center for Radiation Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Khalili Street, P.O. Box: 7193711351, Shiraz, Iran.
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Taheri E, Pourhoseingholi MA, Moslem A, Hassani AH, Mousavi Jarrahi A, Asadzadeh Aghdaei H, Zali MR, Hatami B. The triglyceride-glucose index as a clinical useful marker for metabolic associated fatty liver disease (MAFLD): a population-based study among Iranian adults. J Diabetes Metab Disord 2022; 21:97-107. [PMID: 35673435 PMCID: PMC9167320 DOI: 10.1007/s40200-021-00941-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 11/17/2021] [Indexed: 01/13/2023]
Abstract
BACKGROUND AND AIMS There is a bi-directional association between non-alcoholic fatty liver disease (NAFLD) and insulin resistance in type 2 diabetes mellitus (T2DM) and metabolic syndrome. The triglyceride-glucose (TyG) index is a novel surrogate marker of insulin resistance. In this population-based study, we aimed firstly to investigate the association of the TyG-index with metabolic-associated fatty liver disease (MAFLD) risk. METHODS This case-control study used the data from the first phase of the Persian Cohort Study in Sabzevar. Of 4,241 participants aged 35 to 70 years, we identified and recruited 968 MAFLD cases and 964 age- and sex-adjusted controls. Demographic, lifestyle, anthropometric, and biochemical information were collected. We calculated TyG and a new index combined of TyG and alanine aminotransferase (TyG-ALT). We used the multivariable unconditional logistic regression model to calculate the odds ratios (ORs) of the TyG and TyG-ALT for having MAFLD. RESULTS Among those in the highest relative to the lowest TyG and TyG-ALT tertiles, the multivariable-adjusted ORs were 12.01 (95% CI [confidence interval] 9.03 - 15.98; P trend < 0.001) and 10.89 (95% CI 7.66 - 15.48; P trend = 0.001), respectively. The area under the curves (AUC) for the TyG-index to predict MAFLD was 8.62, resulting in a cut-off value of 8.62 with a sensitivity of 81.66% and specificity of 75.36%. CONCLUSIONS The higher TyG and TyG-ALT scores were significantly positively associated with higher MAFLD risk in the Iranian population.
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Affiliation(s)
- Ehsaneh Taheri
- Student Research Committee, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Amin Pourhoseingholi
- Gasteroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Moslem
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Amir Hossein Hassani
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Mousavi Jarrahi
- Department of Community Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Derosa G, Guasti L, D’Angelo A, Martinotti C, Valentino MC, Di Matteo S, Bruno GM, Maresca AM, Gaudio GV, Maffioli P. Probiotic Therapy With VSL#3® in Patients With NAFLD: A Randomized Clinical Trial. Front Nutr 2022; 9:846873. [PMID: 35685888 PMCID: PMC9172906 DOI: 10.3389/fnut.2022.846873] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
Aim To evaluate if VSL#3® [a high-concentration multi-strain probiotic mix containing one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria (B. breve BB02; B. animalis subspecies [subsp.] lactis BL03, previously identified as B. longum BL03; and B. animalis subsp. lactis BI04, previously identified as B. infantis BI04), and four strains of Lactobacilli (L. acidophilus BA05, L. plantarum BP06, L. paracasei BP07, and L. helveticus BD08, previously identified as L. delbrueckii subsp. bulgaricus BD08)] therapy could improve hepatic parameters. Methods We enrolled 60 Caucasian patients aged ≥ 18 years of either sex with the diagnosis of non-alcoholic fatty liver disease (NAFLD), according to practice guidance, in a double-blind, placebo-controlled study. Patients were randomized to take placebo or VSL#3®, 2 sachets/day in the morning for 3 months. VSL#3® and placebo were self-administered. Results We did not observe any change in body mass index (BMI), circumferences, fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and adiponectin (ADN) with neither treatment. A statistically significant triglycerides (Tg) decrease (p < 0.05 vs. baseline, and p < 0.05 vs. placebo, respectively) and high-sensitivity C-reactive protein (Hs-CRP) decrease (p < 0.05 vs. baseline) was observed in the group of patients being treated with VSL#3® compared with placebo. Transaminases and gamma-glutamyltransferase (γ-GT) were significantly reduced in VSL#3® group (p < 0.05 vs. baseline and placebo, respectively) compared with the placebo group. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and hepatic steatosis index (HSI) were significantly lower than the VSL#3® group (p < 0.05 vs. baseline and placebo, respectively) compared with the placebo group. All patients reported an improvement or the disappearance of hepatic steatosis. Conclusion Probiotic therapy with VSL#3® ameliorates hepatic parameters and echography grading, while reducing Tg and the inflammatory status, without any difference between men and women.
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Affiliation(s)
- Giuseppe Derosa
- Center of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Italian Nutraceutical Society (SINut), Bologna, Italy
- *Correspondence: Giuseppe Derosa,
| | - Luigina Guasti
- Geriatric Division, ASST dei Sette Laghi, University of Insubria, Varese, Italy
| | - Angela D’Angelo
- Center of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
| | - Chiara Martinotti
- S.A.V.E. Studi Analisi Valutazioni Economiche Research Center, Milan, Italy
| | | | - Sergio Di Matteo
- S.A.V.E. Studi Analisi Valutazioni Economiche Research Center, Milan, Italy
| | - Giacomo M. Bruno
- Department of Management Information and Production Engineering, University of Bergamo, Bergamo, Italy
| | - Andrea M. Maresca
- Medical Division, ASST dei Sette Laghi, University of Insubria, Varese, Italy
| | | | - Pamela Maffioli
- Center of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- Italian Nutraceutical Society (SINut), Bologna, Italy
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Yan YL, Xing X, Wang Y, Wang XZ, Wang Z, Yang L. Clinical utility of two-dimensional shear-wave elastography in monitoring disease course in autoimmune hepatitis-primary biliary cholangitis overlap syndrome. World J Gastroenterol 2022; 28:2021-2033. [PMID: 35664960 PMCID: PMC9150059 DOI: 10.3748/wjg.v28.i18.2021] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 12/16/2021] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome has a worse prognosis than AIH or PBC alone. Therefore, accurately staging liver fibrosis and dynamically monitoring disease progression are essential.
AIM To investigate the performance of two-dimensional shear-wave elastography (2D-SWE) for noninvasively staging liver fibrosis and assessing the clinical utility of repeated 2D-SWE for monitoring treatment response in AIH-PBC overlap syndrome.
METHODS A total of 148 patients diagnosed with AIH-PBC overlap syndrome were retrospectively enrolled. Among them, 82 patients had a 2D-SWE follow-up time of more than 1 year. The Scheuer scoring system was used to evaluate stages of hepatic inflammation and liver fibrosis. The performance of 2D-SWE for staging liver fibrosis was evaluated with the liver biopsy. Changes in liver stiffness (LS) measured by 2D-SWE in patients with or without complete biochemical remission were evaluated.
RESULTS LS value was strongly correlated with liver fibrosis stage (Spearman r = 0.84, P < 0.0001). The areas under the receiver operating characteristic curves of LS for diagnosing significant fibrosis (≥ S2), severe fibrosis (≥ S3), and cirrhosis (S4) were 0.91, 0.97, and 0.96, respectively. Patients with complete biochemical remission had a considerable decrease in LS values (P < 0.0001). More importantly, the declined LS in patients with S0-S2 was significantly lower than that in patients with S3-S4 (P = 0.0002). In contrast, patients who failed to achieve biochemical remission had a slight but not significant decrease in LS (P = 0.37).
CONCLUSION LS measured by 2D-SWE is an accurate and reliable method in assessing liver fibrosis, especially for diagnosing severe fibrosis (≥ 3) and monitoring treatment response in patients with AIH-PBC overlap syndrome.
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Affiliation(s)
- Yu-Ling Yan
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Sichuan University, University of Oxford Huaxi Joint for Gastrointestinal Cancer Centre, Chengdu 610207, Sichuan Province, China
| | - Xian Xing
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Sichuan University, University of Oxford Huaxi Joint for Gastrointestinal Cancer Centre, Chengdu 610207, Sichuan Province, China
| | - Yi Wang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Sichuan University, University of Oxford Huaxi Joint for Gastrointestinal Cancer Centre, Chengdu 610207, Sichuan Province, China
| | - Xiao-Ze Wang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Sichuan University, University of Oxford Huaxi Joint for Gastrointestinal Cancer Centre, Chengdu 610207, Sichuan Province, China
| | - Zhi Wang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Sichuan University, University of Oxford Huaxi Joint for Gastrointestinal Cancer Centre, Chengdu 610207, Sichuan Province, China
| | - Li Yang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Sichuan University, University of Oxford Huaxi Joint for Gastrointestinal Cancer Centre, Chengdu 610207, Sichuan Province, China
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Glucocorticosteroids and the Risk of NAFLD in Inflammatory Bowel Disease. Can J Gastroenterol Hepatol 2022; 2022:4344905. [PMID: 35600209 PMCID: PMC9117063 DOI: 10.1155/2022/4344905] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 04/13/2022] [Indexed: 02/08/2023] Open
Abstract
Each year, the incidence of nonalcoholic fatty liver (NAFLD) disease increases. NAFLD is a chronic disease. One of the most common causes of NAFLD is an inadequate lifestyle, which is characterized by a lack or low physical activity and eating highly processed foods rich in saturated fat and salt and containing low amount of fiber. Moreover, disturbances in intestinal microbiome and the use of certain drugs may predispose to NAFLD. NAFLD is an increasingly described disease in patients with inflammatory bowel disease (IBD). Recent data also indicate a frequent coexistence of metabolic syndrome in this group of patients. Certain groups of drugs also increase the risk of developing inflammation, liver fibrosis, and cirrhosis. Particularly important in the development of NAFLD are steroids, which are used in the treatment of many diseases, for example, IBD. NAFLD is one of the most frequent parenteral manifestations of the disease in IBD patients. However, there is still insufficient information on what dose and exposure time of selected types of steroids may lead to the development of NAFLD. It is necessary to conduct further research in this direction. Therefore, patients with IBD should be constantly monitored for risk factors for the development of NAFLD.
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Kim JW, Kim TJ, Kim JE, Na JE, Lee H, Min BH, Lee JH, Rhee PL, Kim JJ. Impact of Helicobacter pylori Eradication on the Risk of Incident Nonalcoholic Fatty Liver Disease: A Cohort Study. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2022. [DOI: 10.7704/kjhugr.2021.0060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Muhammad AG, Hansen FO, Gantzel RH, Rex KF, Villadsen GE, Grønbæk H, Pedersen ML. Non-alcoholic fatty liver disease in patients with type 2 diabetes in Greenland: a register-based cross-sectional study. Int J Circumpolar Health 2022; 81:2065755. [PMID: 35440282 PMCID: PMC9037206 DOI: 10.1080/22423982.2022.2065755] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide due to its close association to the metabolic syndrome of type 2 diabetes mellitus (T2DM), obesity and insulin resistance. However, the prevalence and severity of NAFLD in Greenland remain unexplored. We aimed to estimate the prevalence of liver steatosis and fibrosis among Greenlanders and Danes with T2DM living in Greenland using biochemical surrogate markers. We included 1409 Greenlanders and 182 Danes with T2DM in this register-based cross-sectional study. Greenlanders had higher BMI and plasma lipid levels and lower HbA1c levels compared with Danes (p<0.05). Their median alanine aminotransferase (ALAT) levels were similar. However, more Greenlanders had elevated ALAT levels (20.5% vs. 11.5%, p<0.05). Greenlanders had lower FIB-4 scores than Danes, 0.91 (IQR: 0.66–1.27) vs. 0.97 (IQR: 0.78–1.34), without difference in FIB-4 score categories (p=0.27). The prevalence of advanced fibrosis was low in both populations (1.7–2.6%). In conclusion, Greenlanders with T2DM had better glycaemic control despite higher BMI and plasma lipids. A larger proportion of Greenlanders had elevated plasma ALAT levels, while FIB-4 scores were lower than Danes. These findings suggest that Greenlanders with T2DM may be less likely to develop liver complications than Danes with T2DM in Greenland.
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Affiliation(s)
- Abdullah Ghassan Muhammad
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Steno Diabetes Center Greenland, Nuuk, Greenland
| | - Frederik Orm Hansen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Steno Diabetes Center Greenland, Nuuk, Greenland
| | - Rasmus Hvidbjerg Gantzel
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | - Gerda Elisabeth Villadsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Michael Lynge Pedersen
- Steno Diabetes Center Greenland, Nuuk, Greenland.,Greenland Center for Health Research, Institute of Health and Nature, University of Greenland, Nuuk, Greenland
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Wang W, Liu X, Wei P, Ye F, Chen Y, Shi L, Zhang X, Li J, Lin S, Yang X. SPP1 and CXCL9 Promote Non-alcoholic Steatohepatitis Progression Based on Bioinformatics Analysis and Experimental Studies. Front Med (Lausanne) 2022; 9:862278. [PMID: 35514751 PMCID: PMC9063562 DOI: 10.3389/fmed.2022.862278] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 03/24/2022] [Indexed: 11/13/2022] Open
Abstract
Background and Aims Non-alcoholic fatty liver disease (NAFLD) is a major chronic liver disease worldwide, and non-alcoholic steatohepatitis (NASH) is one of its pathological subtypes. The pathogenesis of NASH has not yet been fully elucidated. The purpose of this study was to identify the hub genes and pathways involved in NASH using bioinformatics methods. The hub genes were confirmed in human and animal models. Materials and Methods Three Gene Expression Omnibus (GEO) datasets (GSE48452, GSE58979, and GSE151158) of NASH patients and healthy controls were included in the study. We used GEO2R to identify differentially expressed genes (DEGs) between NASH patients and healthy controls. Functional enrichment analyses were then performed to explore the potential functions and pathways of the DEGs. In all DEGs, only two genes were highly expressed in NASH patients throughout the three datasets; these two genes, SPP1 and CXCL9, were further studied. Serum and liver tissues from NASH patients and healthy controls were collected. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured in NASH patients and healthy controls. Liver tissues were stained with hematoxylin and eosin. Immunohistochemical staining was used to evaluate the expression levels of the two genes in liver tissues. Male C57BL/6J mice were fed a methionine choline-deficient (MCD) diet for 8 weeks, after which serum ALT and AST levels were measured and liver tissues were stained. Results SPP1 and CXCL9 were the hub genes detected in the three datasets. “Lipid metabolism,” “inflammatory response,” and “lymphocyte activation” were the most significant biological functions in GSE48452, GSE58979, and GSE151158, respectively. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the toll-like receptor signaling pathway was significantly enriched in NASH patients. Serum ALT and AST levels were significantly increased in NASH patients compared to healthy controls. Liver tissues had more serious steatosis, hepatocyte ballooning degeneration, and lobular inflammatory infiltration, and the expression of SPP1 and CXCL9 in liver cells was significantly upregulated in NASH patients compared to healthy controls. MCD diet mice were consistent with NASH patients. Conclusion SPP1 and CXCL9 may play important roles in NASH pathogenesis and could be potential therapeutic targets and biomarkers of NASH in the future. Further experimental studies are needed to confirm our results.
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Affiliation(s)
- Wen Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaojing Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Peiyao Wei
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Feng Ye
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yunru Chen
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Lei Shi
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xi Zhang
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jianzhou Li
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shumei Lin
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Shumei Lin
| | - Xueliang Yang
- Department of Nutrition, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- *Correspondence: Xueliang Yang
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Han AL. Validation of fatty liver index as a marker for metabolic dysfunction-associated fatty liver disease. Diabetol Metab Syndr 2022; 14:44. [PMID: 35317824 PMCID: PMC8939216 DOI: 10.1186/s13098-022-00811-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 03/04/2022] [Indexed: 12/19/2022] Open
Abstract
AIMS Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new nomenclature for nonalcoholic fatty liver. Along with obesity, fatty liver associated with metabolic dysfunction is increasing and has become a serious socioeconomic problem. Non-invasive testing for the confirmation of MAFLD, including the fatty liver index (FLI), can be used as an alternative method for diagnosing steatosis when imaging modalities are not available. To date, few studies have examined the effectiveness and validity of FLI for diagnosing MAFLD. Therefore, this study analyzed the effectiveness and validity of FLI for diagnosing MAFLD. METHODS Medical records of men and women aged ≥ 19 years who underwent abdominal computed tomography (CT) examination at our facility between March 2012 and October 2019 were retrospectively reviewed. A comparative analysis between non-continuous variables was performed using the chi-squared test. The area under receiver operating characteristic (AUROC) curve was used to verify the effectiveness of FLI as a predictive index for MAFLD. RESULTS Analysis of the association between MAFLD and abdominal CT revealed that the sensitivity and specificity of FLI for diagnosing MAFLD were 0.712 and 0.713, respectively. The AUROC of FLI for predicting MAFLD was 0.776. CONCLUSIONS Our study verified the accuracy of FLI for predicting MAFLD using CT. The FLI can be used as a simple and cost-effective tool for screening MAFLD in clinical settings.
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Affiliation(s)
- A Lum Han
- Department of Family Medicine, Wonkwang University Hospital, Sinyong-dong 344-2, Iksan, 54538, Jeonbuk, Korea.
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