Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.

Metabolic-associated fatty liver disease and sarcopenia:A double whammy

The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

Quantitative assessment of self-management in patients with nonalcoholic fatty liver disease: An unmet clinical need

In this editorial we comment on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et al published in a recent issue of the World Journal of Gastroenterology.Non-alcoholic fatty liver disease(NAFLD)represents one of the current challenges in hepatology and public health,due to its continuous growing prevalence and the rising incidence of NAFLD-related fibrosis,non-alcoholic steatohepatitis and cirrhosis.The only effective therapeutic strategy for this dis-ease is represented by encouraging patients to improve their lifestyle through the modification of dietary intake and increased physical exercise,but the effective application of such modifications is often limited by various factors such as lack of information,psychological barriers or poor social support.While poor adherence to a healthy lifestyle can be decisive in determining the clinical outcome,in daily practice there is a lack of quantitative instruments aimed at identifying patients with the lowest adherence to lifestyle changes and higher risk of disease progre-ssion in the course of follow-up.In this article,Zeng et al propose a quantitative scale to assess the grade of adherence of patients with NAFLD to hea-lthy lifestyle intervention,called the Exercise and Diet Adherence Scale(EDAS).This scale,consisting of 33 items divided into 6 dimensions which relates to six subjective aspects in the self-management of NAFLD,has shown a good correlation with the identification of the sub-cohort of patients with the highest reduction in caloric intake,increase in physical exercise,probability of a reduction in liver stiffness measurement and alanine aminotransferase levels.The cor-relation among clinical outcomes and specific dimensions of this scale also highlights the pivotal role of a good and confidential doctor-patient relationship and of an effective communication.There is an urgent need for practical and effective instruments to assess the grade of self-management of NAFLD patients,together with the development of multidisciplinary teams with the aim of applying structured behavioral interventions.

Comprehensive Understanding of Immune Cells in The Pathogenesis of Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and cirrhosis.Although NAFLD is a disease of disordered metabolism,it also involves several immune cell-mediated inflammatory processes,either promoting and/or suppressing hepatocyte inflammation through the secretion of pro-inflammatory and/or anti-inflammatory factors to influence the NAFLD process.However,the underlying disease mechanism and the role of immune cells in NAFLD are still under investigation,leaving many open-ended questions.In this review,we presented the recent concepts about the interplay of immune cells in the onset and pathogenesis of NAFLD.We also highlighted the specific non-immune cells exhibiting immunological properties of therapeutic significance in NAFLD.We hope that this review will help guide the development of future NAFLD therapeutics.

Screening for metabolic dysfunction-associated fatty liver disease:Time to discard the emperor’s clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease

In this editorial,we comment on the article by Chen et al.Metabolic dysfunction-associated fatty liver disease(MAFLD)is a global public health burden whose incidence has risen concurrently with overweight and obesity.Given its detri-mental health impact,early identification of at-risk individuals is crucial.MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy,imaging,or blood biomarkers,and one of the following conditions:Overweight/obesity,type 2 diabetes mellitus,or metabolic dysregulation.However,in large-scale epidemiological studies,liver biopsies are not feasible.The application of techniques such as ultrasonography,computed tomography,magnetic resonance imaging,and magnetic resonance spectroscopy is restricted by their limited sensitivity,low effectiveness,high costs,and need for specialized software.Blood biomarkers offer several advantages,particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical.Analysis of cumulative effects of excess high-normal blood alanine aminotrans-ferase(ALT)levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods.Accordingly,investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring,enabling timely inter-vention and management and improving patient outcomes.

Metabolic dysfunction-associated fatty liver disease and low muscle strength: A comment

The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.

Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan

Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus infection.Methods:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),respectively.In addition,the HSI was less predictive for Fibroscan®-defined fatty liver.Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and FLI.Conclusions:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty liver.In addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

Changes in the terminology and diagnostic criteria of non-alcoholic fatty liver disease:Implications and opportunities

Fatty liver disease(FLD)is a highly prevalent pathological liver disorder.It has many and varied etiologies and has heterogeneous clinical course and outcome.Its proper nomenclature and classification have been problematic since its initial recognition.Traditionally,it was divided into two main categories:Alcoholassociated liver disease and nonalcoholic FLD(NAFLD).Among these,the latter condition has been plagued with nomenclature and classification issues.The two main objections to its use have been the use of negative(non-alcoholic)and stigmatizing(fatty)terms in its nomenclature.Numerous attempts were made to address these issues but none achieved universal acceptance.Just recently,NAFLD has received a new nomenclature from an international collaborative effort based on a rigorous scientific methodology.FLD has been renamed steatotic liver disease(SLD),and NAFLD as metabolic dysfunction-associated SLD.Metabolic dysfunction-associated steatohepatitis was chosen as the replacement terminology for non-alcoholic steatohepatitis.This is a significant positive change in the nomenclature and categorization of FLD and will likely have a major impact on research,diagnosis,treatment,and prognosis of the disease in the future.

Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease worldwide,affecting about 1/4th of the global population and causing a huge global economic burden.To date,no drugs have been approved for the treatment of NAFLD,making the correction of unhealthy lifestyles the principle method of treatment.Identifying patients with poor adherence to lifestyle correction and attempting to improve their adherence are therefore very important.AIM To develop and validate a scale that can rapidly assess the adherence of patients with NAFLD to lifestyle interventions.METHODS The Exercise and Diet Adherence Scale(EDAS)was designed based on com-pilation using the Delphi method,and its reliability was subsequently evaluated.Demographic and laboratory indicators were measured,and patients completed the EDAS questionnaire at baseline and after 6 months.The efficacy of the EDAS was evaluated in the initial cohort.Subsequently,the efficacy of the EDAS was internally verified in a validation cohort.RESULTS The EDAS consisted of 33 items in six dimensions,with a total of 165 points.Total EDAS score correlated significantly with daily number of exercise and daily reduction in calorie intake(P<0.05 each),but not with overall weight loss.A total score of 116 was excellent in predicting adherence to daily reduction in calorie intake(>500 kacl/d),(sensitivity/specificity was 100.0%/75.8%),while patients score below 97 could nearly rule out the possibility of daily exercise(sensitivity/specificity was 89.5%/44.4%).Total EDAS scores≥116,97-115,and<97 points were indicative of good,average,and poor adherence,respectively,to diet and exercise recommendations.CONCLUSION The EDAS can reliably assess the adherence of patients with NAFLD to lifestyle interventions and have clinical application in this population.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.

Transient elastography with controlled attenuation parameter for the diagnosis of colorectal polyps in patients with nonalcoholic fatty liver disease

BACKGROUND The severity of nonalcoholic fatty liver disease(NAFLD)and lipid metabolism are related to the occurrence of colorectal polyps.Liver-controlled attenuation parameters(liver-CAPs)have been established to predict the prognosis of hepatic steatosis patients.AIM To explore the risk factors associated with colorectal polyps in patients with NAFLD by analyzing liver-CAPs and establishing a diagnostic model.METHODS Patients who were diagnosed with colorectal polyps in the Department of Gastroenterology of our hospital between June 2021 and April 2022 composed the case group,and those with no important abnormalities composed the control group.The area under the receiver operating characteristic curve was used to predict the diagnostic efficiency.Differences were considered statistically significant when P<0.05.RESULTS The median triglyceride(TG)and liver-CAP in the case group were significantly greater than those in the control group(mmol/L,1.74 vs 1.05;dB/m,282 vs 254,P<0.05).TG and liver-CAP were found to be independent risk factors for colorectal polyps,with ORs of 2.338(95%CI:1.154–4.733)and 1.019(95%CI:1.006–1.033),respectively(P<0.05).And there was no difference in the diagnostic efficacy between liver-CAP and TG combined with liver-CAP(TG+CAP)(P>0.05).When the liver-CAP was greater than 291 dB/m,colorectal polyps were more likely to occur.CONCLUSION The levels of TG and liver-CAP in patients with colorectal polyps are significantly greater than those patients without polyps.Liver-CAP alone can be used to diagnose NAFLD with colorectal polyps.

Genetically predicted fatty liver disease and risk of psychiatric disorders: A mendelian randomization study

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.

Sex and racial disparities in non-alcoholic fatty liver disease-related cardiovascular events: National inpatient sample analysis (2019)

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases cardiovascular disease(CVD)risk irrespective of other risk factors.However,large-scale cardiovascular sex and race differences are poorly understood.AIM To investigate the relationship between NAFLD and major cardiovascular and cerebrovascular events(MACCE)in subgroups using a nationally representative United States inpatient sample.METHODS We examined National Inpatient Sample(2019)to identify adult hospitalizations with NAFLD by age,sex,and race using ICD-10-CM codes.Clinical and demographic characteristics,comorbidities,and MACCE-related mortality,acute myocardial infarction(AMI),cardiac arrest,and stroke were compared in NAFLD cohorts by sex and race.Multivariable regression analyses were adjusted for sociodemographic characteristics,hospitalization features,and comorbidities.RESULTS We examined 409130 hospitalizations[median 55(IQR 43-66)years]with NFALD.NAFLD was more common in females(1.2%),Hispanics(2%),and Native Americans(1.9%)than whites.Females often reported non-elective admissions,Medicare enrolment,the median age of 55(IQR 42-67),and poor income.Females had higher obesity and uncomplicated diabetes but lower hypertension,hyperlipidemia,and complicated diabetes than males.Hispanics had a median age of 48(IQR 37-60),were Medicaid enrollees,and had non-elective admissions.Hispanics had greater diabetes and obesity rates than whites but lower hypertension and hyperlipidemia.MACCE,all-cause mortality,AMI,cardiac arrest,and stroke were all greater in elderly individuals(P<0.001).MACCE,AMI,and cardiac arrest were more common in men(P<0.001).Native Americans(aOR 1.64)and Asian Pacific Islanders(aOR 1.18)had higher all-cause death risks than whites.CONCLUSION Increasing age and male sex link NAFLD with adverse MACCE outcomes;Native Americans and Asian Pacific Islanders face higher mortality,highlighting a need for tailored interventions and care.

Integrated spatial metabolomics and transcriptomics decipher the hepatoprotection mechanisms of wedelolactone and demethylwedelolactone on non-alcoholic fatty liver disease

Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a“multi-omics”platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It is a pivotal molecule for predicting and protecting against the development of NAFLD.

Genetic Variations and Nonalcoholic Fatty Liver Disease:Field Synopsis,Systematic Meta-Analysis,and Epidemiological Evidence

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria.Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

Mapping global research trends: Nutrition associations with nonalcoholic fatty liver disease - a Scopus bibliometric analysis

BACKGROUND Several bibliometric analyses have been carried out to identify research hotspots and trends in nonalcoholic fatty liver disease(NAFLD)research.Nonetheless,there are still significant knowledge gaps that must be filled to advance our understanding of and ability to treat NAFLD.AIM To evaluate,through bibliometric and visual analysis,the current status of related research,related research frontiers,and the developmental trends in the field of diet and NAFLD.METHODS We retrieved publications about diet and NAFLD published between 1987 and 2022 from Scopus.Next,we used VOSviewer 1.6.20 to perform bibliometric analysis and visualization.RESULTS We found a total of 1905 studies,including 1637(85.93%)original articles and 195(10.24%)reviews,focused on the examination of NAFLD and its correlation with diet that were published between 1987 and 2022.Among the remaining five types of documents,38 were letters,notes,editorials,meeting minutes,or brief surveys,representing 1.99%of the total documents.The countries with the most publications on this topic were China(n=539;28.29%),followed by the United States(n=379;19.90%),Japan(n=133;6.98%),and South Korea(n=127;6.6%).According to the citation analysis,the retrieved papers were cited an average of 32.3 times and had an h-index of 106,with 61014 total citations.The two main clusters on the map included those related to:(1)Inflammation and oxidative stress;and(2)Dietary interventions for NAFLD.CONCLUSION This was the first study to use data taken from Scopus to visualize network mapping in a novel bibliometric analysis of studies focused on diet and NAFLD.After 2017,the two domains that received the most attention were“dietary interventions for NAFL”’and“‘inflammation and oxidative stress implicated in NAFLD and its correlation with diet.”We believe that this study provides important information for academics,dietitians,and doctors,and that additional research on dietary interventions and NAFLD is warranted.