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.

Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)has emerged as a significant health challenge,characterized by its widespread prevalence,intricate natural progression and multifaceted pathogenesis.Although NAFLD initially presents as benign fat accumulation,it may progress to steatosis,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.Mesenchymal stem cells(MSCs)are recognized for their intrinsic self-renewal,superior biocompatibility,and minimal immunogenicity,positioning them as a therapeutic innovation for liver diseases.Therefore,this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways,including glycolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and fibrosis.The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics,and support the development of MSC-based therapy in the treatment of NAFLD.

Excess cardiovascular mortality in men with non-alcoholic fatty liver disease:A cause for concern!

Non-alcoholic fatty liver disease(NAFLD)has emerged as the commonest cause of chronic liver disease worldwide in recent years.With time,our understanding of NAFLD has evolved from an isolated liver condition to a systemic disease with significant manifestations beyond the liver.Amongst them,cardiovascular diseases(CVDs)are the most important and clinically relevant.Recent research supports a strong independent link between NALFD and CVD beyond the shared risk factors and pathophysiology.Female sex hormones are well known to not only protect against CVD in pre-menopausal females,but also contribute to improved adipose tissue function and preventing its systemic deposition.Recent research highlights the increased risk of major adverse cardiovascular-cerebral events(MACCE)amongst male with NAFLD compared to females.Further,racial variation was observed in MACCE outcomes in NAFLD,with excess mortality in the Native Americans and Asian Pacific Islanders compared to the other races.

Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease:Mechanism,clinical evidence,and prospect

The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.

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.

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.

From non-alcoholic fatty liver disease to metabolic-associated steatotic liver disease:Rationale and implications for the new terminology

Non-alcoholic fatty liver disease(NAFLD)was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of alcohol.Alcoholic liver disease(ALD)has many similarities to NAFLD in both pathogenesis and histology.This entity is now the most prevalent chronic liver disease worldwide as a consequence of the epidemic of obesity.Attempts to incorporate the importance of the metabolic syndrome in the development of steatosis resulted in the renaming of NAFLD as metabolic-associated fatty liver disease.This new term,however,has the disadvantage of the use of terms that may be perceived as derogatory.The terms fatty and non-alcoholic have negative connotations in many cultures.In addition,non-alcoholic is not usually a term applicable to pediatric cases of hepatic steatosis.Recently,an international collaborative effort,with participants from 56 countries,after a global consultation process,recommended to change the nomenclature to steatotic liver disease-including metabolic dysfunction-associated steatotic liver disease,metabolic-associated steatohepatitis and metabolic dysfunction-associated ALD.The new terminology is consistent with most of the previously published epidemiological studies and will have a major impact on research into diagnosis,prognosis and treatment.

Consumption of sugary beverages,genetic predisposition and the risk of depression:a prospective cohort study

Background The associations between sugary beverages and genetic predisposition to depression risk remain unclear.Aims This study aimed to investigate the associations of sugar-sweetened beverages(SSBs),artificially sweetened beverages(ASBs)and natural juices(NJs)with depression and to assess whether these associations were modified by genetic predisposition.Methods We used data from the UK Biobank of 180599 individuals aged 39-72 years who were depression-free at baseline.Dietary intake of SSBs,ASBs and NJs was accessed by a 24-hour dietary recall between 2009 and 2012.The Polygenic Risk Score for depression was estimated and categorised as low(lowest tertile),intermediate(tertile 2)and high(highest tertile),.Cox proportional hazard and substitution models were conducted to evaluate hazard ratios(HRs)and 95%Cls.Results Over the 12-year follow-up,4915 individuals developed depression.Higher consumption(>2 units/day)of SSBs(HR:1.26,95%CI 1.12 to 1.43)and ASBs(HR:1.40,95%Cl 1.23 to 1.60)were both associated with an increased risk of depression.However,moderate consumption(>0-1 units/day)of NJs was associated with a lower risk of depression(HR:0.89,95%CI 0.83 to 0.95).Furthermore,genetic predisposition did not modify these associations(p interaction>0.05).In substitution models,the HRs for depression risk were 0.94(95%CI 0.89 to 0.99)and 0.89(95%CI 0.85 to 0.94),respectively,when 1 unit/day of SSBs or ASBs was replaced by an equivalent intake of NJs.Conclusions Higher consumption of SSBs and ASBs was associated with an increased risk of depression;in contrast,moderate consumption of NJs was inversely associated with a lower risk of depression.In theory,substituting SSBs and ASBswith NJs would suppose a reduction of depression risk.

Taxing sugar-sweetened beverages in China:By volume or sugar content? A consumer welfare approach

Using scanner data on the consumption of packaged liquid beverages by Chinese urban households,we estimated the price elasticity of various beverages and compared the effects of volume-based versus sugar-content-based taxation strategies on consumer welfare.Compared to the volume-based tax,the sugar-content-based beverage tax was predicted to cost less in compensating variation under the same amount of sugar reduced,indicating that taxation based on sugar content may be more efficient in preserving consumer welfare.Further comparison across different socioeconomic groups reveals that,given current beverage consumption status in China,the efficiency advantage of the sugar-content-based taxation strategy is more pronounced than that of the volume-based taxation.Our conclusions can provide insights for the food industry and the government to reduce the sugar content in beverages.

Adulteration detection of plant protein beverages by UPLC-MS/MS based on signature peptide of allergen

Plant protein beverage adulteration occurs frequently,which may cause health problems for consumers due to the hidden allergens.Hence,a novel method was developed for authentication by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).Almond,peanut,walnut and soybean were hydrolyzed,followed by separation by NanoLC-Triple TOF MS.The obtained fingerprints were identified by ProteinPilotTM combined with Uniprot,and 16 signature peptides were selected.Afterwards,plant protein beverages treated by trypsin hydrolysis were analyzed with UPLC-MS/MS.This method showed a good linear relationship with R2>0.99403.The limit of quantification(LOQ)were 0.015,0.01,0.5 and 0.05 g/L for almond,peanut,walnut and soybean,respectively.Mean recoveries ranged from 84.77%to 110.44%with RSDs<15%.The developed method was successfully applied to the adulteration detection of 31 plant protein beverages to reveal adulteration and false labeling.Conclusively,this method could provide technical support for authentication of plant protein beverages to protect the rights and health of consumers.

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.

Health effects of fruit juices and beverages with varying degrees of processing

The degree of processing is rarely considered an independent factor in the health effects of fruit juices and beverages(FJBs)consumption.In fact,the consumption of ultra-processed foods has been shown to pose health risks.In this study,we first integrated 4 systems used to classify the degree of food processing and then classified FJBs into three major categories,low(minimal),moderate and high.Second,we compared the differences in attitudes towards FJBs in dietary guidelines.Third,we integrated the results of existing epidemiological surveys,randomized controlled trials,and animal experiments to explore the health risks associated with consuming FJBs.Deepening the processing of FJBs has been found to lead to an increased risk of diseases.Dietary pattern,nutrients,addition agents and consumer preferences may be influential factors.Finally,we investigated whether there were any changes in the health benefits of 100%fruit juices produced by different processing methods.In conclusion,minimally/moderately processed 100%fruit juices provide more health benefits than highly processed fruit beverages.The results support the need to consider the extent of FJBs processing in future studies to adjust official nutritional recommendations for beverage consumption.

The gut-liver axis mechanism of increased susceptibility to non-alcoholic fatty disease in female offspring rats with prenatal caffeine exposure

Caffeine intake during pregnancy is common,while its effect on gut microbiota composition of offspring and the relationship with susceptibility to adult diseases remains unclear.This study aimed to confirm the effects of prenatal caffeine exposure(PCE)on the gut microbiota composition and its metabolites in female offspring rats,and to further elucidate its underlying mechanism and intervention targets in adult non-alcoholic fatty disease(NAFLD).The results showed that the gut microbiota of PCE female offspring at multiple time points from infancy to adolescence were significantly changed with depletion of butyric acid-producing bacteria,leading to a decrease in butyric acid in adulthood.It was also found that PCE female offspring rats were sensitive to NAFLD induced by a postnatal high-fat diet(HFD),which is mainly related to the enhancement of hepatic triglyceride synthesis function.Through mechanism exploration,we found that HFD further reduced the fecal and serum butyric acid levels in the PCE female offspring,which was significantly negatively correlated with hepatic SREBP-1c/FASN mRNA expression and triglyceride level.In vivo and in vitro experiments confirmed that sodium butyrate(NaB)supplementation could reduce hepatic lipid accumulation through MCT1/GPR109A-AMPK,thereby effectively decreasing the susceptibility to NAFLD in the PCE female offspring rats.

Higher intakes of lysine,threonine and valine are inversely associated with non-alcoholic fatty liver disease risk:a community-based case-control study in the Chinese elderly

The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearity<0.05).Conclusion:The present study demonstrated that the dietary increases in milk,eggs and deep-sea fish,which are rich in the amino acids,might contribute to protecting against NAFLD in the elderly.

Effective roles of exercise and diet adherence in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is characterized by symptoms of excessive fat accumulation and steatosis in the liver without alcohol intake in patients.The associated pathogenic mechanism is not completely understood and there are no specific drugs for patients with NAFLD.Exercise and diet adherence are the best options for the management of NAFLD patients.Questionnaire associated analysis models of adherence to these interventions are used to assess their effectiveness in the management of NAFLD patients using specificity,sensitivity,and so on.Studies have indicated that the relative ratio of NAFLD can be reduced by physical activity with diet control.In the future,the pathogenesis of NAFLD should be clarified with stratified efforts to develop appropriate drugs,and both exercise and diet adherence should be optimized using better questionnaire design and evaluation models for patients with NAFLD.

Management of non-alcoholic fatty liver disease:Lifestyle changes

In this editorial,we commented on a recently released manuscript by Zeng et al in the World Journal of Gastroenterology.We focused specifically on lifestyle changes in patients with non-alcoholic fatty liver disease(NAFLD).NAFLD is a hepatic manifestation of the metabolic syndrome,which ultimately leads to advanced hepatic fibrosis,cirrhosis,and hepatocellular carcinoma and affects more than 25%of the population globally.Existing therapeutic strategies against NAFLD such as pharmacologic therapies focus on liver protection,anti-inflammation,and regulating disease-related metabolic disorder symptoms.Although several drugs are in late-stage development,potent drugs against the diseases are lacking.Additionally,existing surgical approaches such as bariatric surgery are not routinely used to treat NAFLD.Intervening in patients’unhealthy lifestyles,such as weight loss through dietary changes and exercises to ameliorate patientassociated metabolic disorders and metabolic syndrome,is the first-line treatment for patients with NAFLD.With sufficient intrinsic motivation and adherence,the management of unhealthy lifestyles can reduce the severity of the disease,improve the quality of life,and increase the survival expectancy of patients with NAFLD.

Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization

Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompoundwith antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN canameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying thesebeneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipidaccumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis(NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line andthe liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type andthe regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophageM2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovereda new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFNmight be protective against NASH.

Bioactive constituents and action mechanism of Xiaoyao San for treatment of non-alcoholic fatty liver disease

Xiaoyao San(XYS)is a classic Chinese medicine prescription.It is traditionally used to relieve syndrome of“liver stagnation and spleen deficiency”,a common syndrome type in traditional Chinese medicine,through soothing liver,tonifying spleen,and nourishing blood.Correspondingly,XYS has long application in the treatment of depression,dyspepsia and liver diseases.Given the rising of cutting-edge researches on XYS,there’s a significant need to diligently uncover the bioactive constituents and action mechanisms of XYS for treating non-alcoholic fatty liver disease accordingly.

Correlation between non-alcoholic fatty liver disease and metabolic parameters in persons with newly diagnosed type 2 diabetes mellitus

BACKGROUND There are limited studies investigating the association between type 2 diabetes mellitus(T2DM)and non-alcoholic fatty liver disease(NAFLD)in the region of Bihar,India.AIM To estimate the prevalence of NAFLD in persons with newly diagnosed T2DM in the population of North Bihar,India.METHODS This single centre cross-sectional study was undertaken in the Research Centre for Diabetes Hypertension and Obesity,Samastipur,Bihar,India.Data were collected from persons newly diagnosed with T2DM or those diagnosed within 6 months of when the study was conducted between December 2022 to May 2023.RESULTS A total of 148 people with newly diagnosed T2DM were included(median age 47 years,46.6%female)and 109 patients with liver disease on ultrasound evaluation.The persons with liver disease consumed more fats and oils(88.1%vs 74.4%,P=0.042)and they had significantly greater body mass index(27.4 vs 23.0,P<0.001),waist circumference(37 vs 33,P<0.001),and waist-to-hip ratio(1.00 vs 0.70,P=0.025).Females were associated with greater liver disease[odds ratio(OR):3.09,95%confidence interval(CI):1.09-8.80,P=0.32].Waist circumference(OR:1.42,95%CI:1.22-1.66,P<0.001)and low-density lipoprotein cholesterol(OR:1.01,95%CI:1.01-1.02,P=0.048)were associated with any liver disease.The factors most associated with grade 2/3 liver disease was right upper quadrant pain or heaviness(OR:5.22,95%CI:1.40-19.41,P=0.14),greater income(OR:3.58,95%CI:1.28-10.04,P=0.015)and waist circumference(OR:1.31,95%CI:1.02-1.69,P=0.036).CONCLUSION NAFLD is common in new/recently diagnosed T2DM and disease burden is high and common among patients who are either high consumers of fats and oils or have obesity-associated markers.

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients

BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty liver disease(NAFLD).Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.AIM To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.METHODS A training model was developed involving 399 participants,comprising 113 healthy controls(HCs),134 individuals with T2DM without NAFLD,and 152 individuals with T2DM and NAFLD.External validation encompassed 172 participants.NAFLD patients were divided based on liver fibrosis scores.The analytical approach employed univariate testing,orthogonal partial least squares-discriminant analysis,logistic regression,receiver operating characteristic curve analysis,and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.RESULTS Compared to HCs,both T2DM and NAFLD groups exhibited diminished levels of specific BAs.In UFAs,particular acids exhibited a positive correlation with NAFLD risk in T2DM,while theω-6:ω-3 UFA ratio demonstrated a negative correlation.Levels ofα-linolenic acid andγ-linolenic acid were linked to significant liver fibrosis in NAFLD.The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.CONCLUSION This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM,proposing their potential as biomarkers in the pathogenesis of NAFLD.