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Nonalcoholic Fatty Liver Disease: Focus on New Biomarkers and Lifestyle Interventions.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, characterized from pathological changes in lipid and carbohydrate metabolism. Its main characteristics are excessive lipid accumulation and oxidative stress, which create a lipotoxic environment in hepatocytes leading to liver injury. Recently, many studies have focused on the identification of the genetic and epigenetic modifications that also contribute to NAFLD pathogenesis and their prognostic implications. The present review is aimed to discuss on cellular and metabolic alterations associated with NAFLD, which can be helpful to identify new noninvasive biomarkers. The identification of accumulated lipids in the cell membranes, as well as circulating cytokeratins and exosomes, provides new insights in understanding of NAFLD. This review also suggests that lifestyle modifications remain the main prevention and/or treatment for NAFLD.

SUBMITTER: Notarnicola M

PROVIDER: S-EPMC8069944 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Nonalcoholic Fatty Liver Disease: Focus on New Biomarkers and Lifestyle Interventions.

Notarnicola Maria M Osella Alberto Ruben AR Caruso Maria Gabriella MG Pesole Pasqua Letizia PL Lippolis Antonio A Tutino Valeria V Bonfiglio Caterina C De Nunzio Valentina V Scavo Maria Principia MP Mirizzi Antonella A Franco Isabella I Lippolis Tamara T D'Alessandro Rosalba R Refolo Maria Grazia MG Messa Caterina C

International journal of molecular sciences 20210409 8

Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, characterized from pathological changes in lipid and carbohydrate metabolism. Its main characteristics are excessive lipid accumulation and oxidative stress, which create a lipotoxic environment in hepatocytes leading to liver injury. Recently, many studies have focused on the identification of the genetic and epigenetic modifications that also contribute to NAFLD pathogenesis and their prognost ...[more]

PMID: 33918878

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Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) is the most common liver disease. Metabolism-related genes significantly influence the onset and progression of the disease. Hence, it is necessary to screen metabolism-related biomarkers for the diagnosis and treatment of NAFLD patients.MethodsGSE48452, GSE63067, and GSE89632 datasets including nonalcoholic steatohepatitis (NASH) and healthy controls (HC) analyzed in this study were retrieved from the Gene Expression Omnibus (GEO) database. First, differentially expressed genes (DEGs) between NASH and HC samples were obtained. Next, metabolism-related DEGs (MR-DEGs) were identified by overlapping DEGs and metabolism-related genes (MRG). Further, a protein-protein interaction (PPI) network was developed to show the interaction among MR-DEGs. Subsequently, the "Least absolute shrinkage and selection operator regression" and "Random Forest" algorithms were used to screen metabolism-related genes (MRGs) in patients with NAFLD. Next, immune cell infiltration and gene set enrichment analyses (GSEA) were performed on these metabolism-related genes. Finally, the expression of metabolism-related gene was determined at the transcription level.ResultsFirst, 129 DEGs related to NAFLD development were identified among patients with nonalcoholic steatohepatitis (NASH) and healthy control. Next, 18 MR-DEGs were identified using the Venn diagram. Subsequently, four genes, including AMDHD1, FMO1, LPL, and P4HA1, were identified using machine learning algorithms. Moreover, a regulatory network consisting of four genes, 25 microRNAs (miRNAs), and 41 transcription factors (TFs) was constructed. Finally, a significant increase in FMO1 and LPL expression levels and a decrease in AMDHD1 and P4HA1 expression levels were observed in patients in the NASH group compared to the HC group.ConclusionMetabolism-related genes associated with NAFLD were identified, containing AMDHD1, FMO1, LPL, and P4HA1, which provide insights into diagnosing and treating patients with NAFLD.

Project description:BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing in parallel with the epidemic of obesity and metabolic syndrome. Lifestyle modification is a crucial strategy for the treatment of NAFLD, which can lead to a reduction in liver fat with concomitant weight loss. The use of eHealth technologies is an effective approach to improve health outcomes in patients as they do not have any time and space limitations.ObjectiveThis study aimed to evaluate published eHealth intervention studies for the improvement of lifestyle modifications among patients with NAFLD and to provide recommendations for future studies.MethodsWe conducted a systematic review and meta-analysis. Five electronic databases (PubMed, Cochrane Central, CINAHL, Embase, and Web of Science) were searched for studies reporting the effect of lifestyle modification intervention using eHealth in patients with NAFLD published from inception to November 3, 2022. Study selection, data extraction, and quality assessment were performed by 3 researchers independently. The quality of included studies was assessed using the Cochrane risk of bias tool and the Risk of Bias Assessment Tool for Nonrandomized Studies.ResultsIn total, 2688 records were identified, and 41 full-text articles were assessed. Seven studies were included in the systematic review. The participants of all interventions were 1257 individuals with NAFLD, and the mean age ranged from 38.3 to 57.9 years. The duration of the interventions was 3-24 months, and all interventions were categorized into 3 types: internet-based computers, telephones, and mobile apps. Of these, 4 studies were randomized controlled trials and were included in the meta-analysis: 3 studies for body weight and BMI and 4 studies for alanine aminotransferase (ALT) and aspartate aminotransferase (AST). According to the meta-analysis, clear improvements in BMI (P=.02; 95% CI -1.01 to -0.10), AST (P=.02; 95% CI -1.22 to -0.13), and ALT (P=.01; 95% CI -1.28 to -0.15) were observed in the eHealth intervention as compared with the control groups.ConclusionsLifestyle modification interventions using eHealth technologies are significantly effective for BMI, AST, and ALT in patients with NAFLD. Future research should conduct interventions with larger sample sizes and evaluate whether these interventions have sustained benefits, and how we can make these eHealth methods most effective on a large scale.

Dataset Information

Nonalcoholic Fatty Liver Disease: Focus on New Biomarkers and Lifestyle Interventions.

Publications

Nonalcoholic Fatty Liver Disease: Focus on New Biomarkers and Lifestyle Interventions.

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