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.

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.

Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

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.

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.

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.

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.

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.

Effects of forsythin extract in Forsythia leaves on intestinal microbiota and short-chain fatty acids in rats fed a high-fat diet

Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa leaves increased the abundance of the intestinal microbiota,ameliorated intestinal microbiota disorders and inhibited the increase in total SCFA content in the intestinal tract in rats with obesity induced by a high-fat diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.

Glucokinase regulatory protein rs780094 polymorphism is associated with type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease, and nephropathy

In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.

Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such complications.However,the metabolic profile of SCFAs in patients with ICP remains unclear.AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups.Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal serum.Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of change.Furthermore,the SCFA levels in maternal serum and cord blood were significantly positively correlated.Notably,certain maternal serum SCFAs,specifically caproic and acetic acids,demonstrated excellent diagnostic efficiency for ICP.

Non-alcoholic fatty liver disease and sleep disorders

Studies have shown that non-alcoholic fatty liver disease(NAFLD)may be associated with sleep disorders.In order to explore the explicit relationship between the two,we systematically reviewed the effects of sleep disorders,especially obstructive sleep apnea(OSA),on the incidence of NAFLD,and analyzed the possible mechanisms after adjusting for confounding factors.NAFLD is independently associated with sleep disorders.Different sleep disorders may be the cause of the onset and aggravation of NAFLD.An excessive or insufficient sleep duration,poor sleep quality,insomnia,sleep-wake disorders,and OSA may increase the incidence of NAFLD.Despite that some research suggests a unidirectional causal link between the two,specifically,the onset of NAFLD is identified as a result of changes in sleep characteristics,and the reverse relationship does not hold true.Nevertheless,there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD.Further research is needed to establish a clear relationship between NAFLD and sleep disorders.This will lay the groundwork for earlier identification of potential patients,which is crucial for earlier monitoring,diagnosis,effective prevention,and treatment of NAFLD.

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.

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.

In-hospital outcomes in COVID-19 patients with non-alcoholic fatty liver disease by severity of obesity:Insights from national inpatient sample 2020

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular diseases independently of other risk factors.However,data on its effect on cardiovascular outcomes in coronavirus disease 2019(COVID-19)hospitalizations with varied obesity levels is scarce.Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels.AIM To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity.METHODS COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease-10 CM codes in the 2020 National Inpatient Sample database.Overweight and Obesity Classes Ⅰ,Ⅱ,and Ⅲ(body mass index 30-40)were compared.Major adverse cardiac and cerebrovascular events(MACCE)(all-cause mortality,acute myocardial infarction,cardiac arrest,and stroke)were compared between groups.Multivariable regression analyses adjusted for sociodemographic,hospitalization features,and comorbidities.RESULTS Our analysis comprised 13260 hospitalizations,7.3% of which were overweight,24.3% Class Ⅰ,24.1% Class Ⅱ,and 44.3% Class Ⅲ.Class Ⅲ obesity includes younger patients,blacks,females,diabetics,and hypertensive patients.On multivariable logistic analysis,Class Ⅲ obese patients had higher risks of MACCE,inpatient mortality,and respiratory failure than Class Ⅰ obese patients.Class Ⅱ obesity showed increased risks of MACCE,inpatient mortality,and respiratory failure than Class I,but not significantly.All obesity classes had non-significant risks of MACCE,inpatient mortality,and respiratory failure compared to the overweight group.CONCLUSION Class Ⅲ obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class Ⅰ.Using the overweight group as the reference,unfavorable outcomes were not significantly different.Morbid obesity had a greater risk of MACCE regardless of the referent group(overweight or Class Ⅰ obese)compared to overweight NAFLD patients admitted with COVID-19.

Yiqi Tongluo capsule has protective effects against non-alcoholic fatty liver disease via regulating PI3K/AKT signaling

Background:Oxidative stress is one of the key elements in the progression of non-alcoholic fatty liver disease(NAFLD),and Yiqi Tongluo capsule(YTC)have a variety of physiological activities which include antioxidant.The purpose of this investigation was to discover the potential mechanisms of YTC ameliorates NAFLD.Methods:In this investigation,a high-fat diet(HFD)was adopted to establish a NAFLD mouse model.Liver samples were stained for oil red O and hematoxylin and eosin staining.The levels of total cholesterol(TC),triglyceride(TG),malondialdehyde(MDA),and superoxide dismutase(SOD)in the tissues were also detected.Network pharmacology was analyzed to filter out the key ingredients and targets of effect of YTC for the therapy of NAFLD.Subsequently,free fatty acids(FFA)was applied to induce Aml12 cells for in vitro experiments,and the cell samples were stained with oil red O and assayed for TC,TG,MDA,and SOD contents.At last,the Western blot technique was used to illuminate the pathway by which YTC plays a protective role against NAFLD.Results:Histopathological results demonstrated that YTC ameliorated tissue damage in the HFD-induced mouse model.At the same time,it also reduced the contents of TC,TG,MDA and increased the expression of SOD in the liver tissue of NAFLD mouse model.All of these findings demonstrate that YTC can play a role in the treatment of NAFLD by ameliorating oxidative stress.Network analysis of YTC ameliorates NAFLD mainly by modulating the PI3K-Akt signaling pathway.Follow-up in vitro experiments revealed that FFA caused lipid accumulation in Aml12 cells,which was dramatically reduced by YTC.Meanwhile,YTC could remarkably reduce the FFA-induced elevation of TC,TG,and MDA contents,and reverse the FFA-induced reduction of SOD contents.Western blot was verified for the PI3K-Akt signaling pathway.It was found that FFA could remarkably decrease the expression of p-PI3K,p-Akt,and p-GSK-3βproteins,which could be significantly increased after YTC treatment.Conclusions:The combination of network analysis prediction and experimental verification was used to identify the therapeutic effect of YTC on NAFLD.The protective effect was achieved by YTC through upregulation of PI3K-Akt-GSK-3βpathway.

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.

Non-alcoholic fatty liver disease in type 2 diabetes:Emerging evidence of benefit of peroxisome proliferator-activated receptors agonists and incretin-based therapies

Nonalcoholic fatty liver disease(NAFLD)is a global epidemic,affecting more than half of the people living with type 2 diabetes(T2D).The relationship between NAFLD and T2D is bidirectional and the presence of one perpetuates the other,which significantly increases the hepatic as well as extrahepatic complications.Until recently,there was no approved pharmacological treatment for NAFLD/nonalcoholic steatohepatitits(NASH).However,there is evidence that drugs used for diabetes may have beneficial effects on NAFLD.Insulin sensitizers acting through peroxisome proliferator-activated receptor(PPAR)modulation act on multiple levels of NAFLD pathogenesis.Pioglitazone(PPARγ agonist)and saroglitazar(PPARα/γagonist)are particularly beneficial and recommended by several authoritative bodies for treating NAFLD in T2D,although data on biopsyproven NASH are lacking with the latter.Initial data on elafibanor(PPARα/δ agonist)and Lanifibranor(pan PPAR agonist)are promising.On the other hand,incretin therapies based on glucagon-like peptide-1(GLP-1)receptor agonists(GLP-1RA)and dual-and triple-hormone receptor co-agonists reported impressive weight loss and may have anti-inflammatory and antifibrotic properties.GLP-1 RAs have shown beneficial effects on NAFLD/NASH and more studies on potential direct effects on liver function by dual-and triple-agonists are required.Furthermore,the long-term safety of these therapies in NAFLD needs to be established.Collaborative efforts among healthcare providers such as primary care doctors,hepatologists,and endocrinologists are warranted for selecting patients for the best possible management of NAFLD in T2D.

Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)includes a spectrum of conditions,progressing from mild steatosis to advanced fibrosis.Sarcopenia,characterized by decreased muscle strength and mass,shares common pathophysiological traits with NAFLD.An association exists between sarcopenia and increased NAFLD prevalence.However,data on the prevalence of sarcopenia in NAFLD and its impact on the outcomes of NAFLD remain inconsistent.AIM To analyze the prevalence and outcomes of sarcopenia in patients with NAFLD.METHODS We conducted a comprehensive search for relevant studies in MEDLINE,Embase,and Scopus from their inception to June 2023.We included studies that focused on patients with NAFLD,reported the prevalence of sarcopenia as the primary outcome,and examined secondary outcomes,such as liver fibrosis and other adverse events.We also used the Newcastle-Ottawa scale for quality assessment.RESULTS Of the 29 studies included,the prevalence of sarcopenia in NAFLD varied widely(1.6%to 63.0%),with 20 studies reporting a prevalence of more than 10.0%.Substantial heterogeneity was noted in the measurement modalities for sarcopenia.Sarcopenia was associated with a higher risk of advanced fibrosis(odd ratio:1.97,95%confidence interval:1.44-2.70).Increased odds were consistently observed in fibrosis assessment through biopsy,NAFLD fibrosis score/body mass index,aspartate aminotransferase to alanine aminotransferase ratio,diabetes(BARD)score,and transient elastography,whereas the fibrosis-4 score showed no such association.Sarcopenia in NAFLD was associated with a higher risk of steatohepatitis,insulin resistance,cardiovascular risks,and mortality.CONCLUSION This systematic review highlights the critical need for standardized diagnostic criteria and measurement methods for sarcopenia in NAFLD patients.The variability in study designs and assessment methods for sarcopenia and liver fibrosis may account for the inconsistent findings.This review demonstrates the multidimensional impact of sarcopenia on NAFLD,indicating its importance beyond liver-related events to include cardiovascular risks,mortality,and metabolic complications.

The effect of Jiangan Xiaozhi Formula on oxidative stress and inflammatory factors in patients with non-alcoholic fatty liver disease

Objective:To investigate the effects of Jiangan Xiaozhi Formula(JGXZ)on oxidative stress and inflammatory factors in patients with non-alcoholic fatty liver disease(NAFLD).Methods:Between September 2022 and December 2023,our hospital admitted a total of 58 patients with NAFLD.These patients were split into two groups at random:one for experimentation and the other for control.There were 27 patients in the experimental group at the end,compared to 26 in the control group,reasonable exercise,weight management,lipid regulation,and oral polyene phosphatidylcholine capsules(PPC).The experimental group received JGXZ in addition to the above treatments for 12 consecutive weeks.Changes in Traditional Chinese Medicine(TCM)syndrome scores,blood lipids,liver function indicators,the levels of oxidative stress markers,such as malondialdehyde(MDA),glutathione peroxidase(GSH-Px),and superoxide dismutase(SOD),as well as serum inflammatory factors,such as interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α),were measured both before and after treatment.Results:After treatment,both groups showed significant reductions in TCM syndrome scores(P<0.05)and improvements in blood lipids,liver function indicators,inflammatory factors,and oxidative stress markers(P<0.05).Improvements were noticeably better in the experimental group than in the control group.(P<0.05).Conclusion:JGXZ can significantly improve clinical symptoms,regulate blood lipids,and protect liver function in patients with NAFLD.Its mechanism may be related to inhibiting inflammatory responses and regulating the balance of the oxidation-antioxidation system.