Introduction:Advances in HIV management have transformed HIV into a chronic condition,resulting in improved prognosis and increased survival among people living with HIV(PLWH).Traditional risk factors for metabolic dy...Introduction:Advances in HIV management have transformed HIV into a chronic condition,resulting in improved prognosis and increased survival among people living with HIV(PLWH).Traditional risk factors for metabolic dysfunction-associated steatotic liver disease(MASLD)—including dyslipidemia—are prevalent in PLWH.This systematic review and meta-analysis aim to synthesize current evidence on lipid profile disturbances as contributors to MASLD in PLWH.Methods:This systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines and registered in PROSPERO with registration number CRD420251054477.We searched seven databases to identify studies reporting the prevalence and characteristics of MASLD in PLWH.Meta-analysis was conducted using Review Manager 5.4.1.Mean differences(MDs)were calculated using a random-effects model.Risk of bias was assessed using the ROBINS-E tool.Results:A total of 17 studies comprising 3933 HIV-positive participants were included,among whom 1226(37%)had MASLD.Male sex was significantly associated with MASLD(OR=1.57;95%CI:1.13-2.17;p=0.007).MASLD was significantly associated with higher body mass index(BMI)(MD=3.23 kg/m^(2);p<0.00001).Lipid profile analysis revealed that MASLD patients had higher total cholesterol(MD=6.62 mg/dL;p=0.01),low density lipoprotein(LDL)(MD=3.83 mg/dL;p=0.01),triglycerides(MD=63.02 mg/dL;p<0.00001),and lower high density lipoprotein(HDL)(MD=-3.73 mg/dL;p<0.0001).Conclusion:This study demonstrates a significant difference in lipid profiles(higher total cholesterol,LDL,triglycerides,and lower HDL)among PLWH who develop MASLD,suggesting a potential metabolic signature associated with this comorbidity.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resu...Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.展开更多
MASLD in China:an under-recognized public health problem Epidemic characteristics of metabolic dysfunction-associated steatotic liver disease(MASLD)in China As one of the most common chronic non-infectious liver disea...MASLD in China:an under-recognized public health problem Epidemic characteristics of metabolic dysfunction-associated steatotic liver disease(MASLD)in China As one of the most common chronic non-infectious liver diseases,metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),affects one quarter of the world’s population,is closely related to diabetes and obesity[1,2].展开更多
This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellula...This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.展开更多
Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological...Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological interventions,thereby negatively affecting the prognosis.This review discusses the clinical problems associated with increased fatigue,explores diagnostic methods,considers key pathogenetic mechanisms of this symptom development(including neuroinflammation,hyperammonemia,mitochondrial and muscle dysfunction,sleep disorders,changes in the composition of gut microbiota),and describes the role of interorgan communication(the liver-brain and gut-brain axes)in the formation of the central link of fatigue.The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue,which would include not only the impact on metabolic disorders,but also on neurophysiological and behavioral factors.Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention(which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy)and improve the prognosis of patients with this chronic liver disease.展开更多
In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two ...In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two major contributors to the global burden of liver disease.By analyzing clinical characteristics,metabolic parameters,immune profiles,and liver pathology,Zhao et al comprehensively explored how MASLD influences the presentation,severity,and prognosis of DILI.Additionally,this study underscores the importance of structured diagnostic tools,such as the Roussel Uclaf Causality Assessment Method,to accurately assess the causality of DILI within the MASLD population.Although this study provides valuable insights,limitations such as its retrospective design and cohort heterogeneity underscore the need for future prospective research to refine diagnostic approaches and therapeutic strategies.展开更多
Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus(T2DM)and also in those with metabolic dysfunction-associated steatotic liver disease(MASLD).In this editorial,we comme...Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus(T2DM)and also in those with metabolic dysfunction-associated steatotic liver disease(MASLD).In this editorial,we comment on the results of a meta-analysis published by Shetty et al that shows an addictive risk for cardi-ovascular events when both pathologies are together.Patients with MASLD and T2DM have the worst prognosis related to liver disease since they have a higher risk for metabolic dysfunction-associated steatohepatitis,disease progression,and hepatocarcinoma.The meta-analysis included 370013 participants and showed that,although with high heterogeneity,there is a higher prevalence of cardio-vascular events in patients with T2DM when MASLD is diagnosed compared to those without MASLD.Hence,MASLD and T2DM may have a new interplay regarding cardiovascular outcomes in addition to the already known liver-related outcomes.展开更多
The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized...The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized from cholesterol in hepatocytes,not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor(FXR)and Takeda G-protein-coupled receptor 5.Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally,closely linked with obesity,insulin resis-tance,and other components of metabolic syndrome.In MASLD,the metabolism of BAs is markedly disrupted,resulting in alterations in their synthesis,compo-sition,and signaling activity.These changes contribute to hepatic steatosis,inflammation,and fibrosis,thereby exacerbating metabolic dysfunction and liver damage.The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity,but also as active mediators of its pathogenesis.Modulators of BA signaling pathways,especially FXR agonists,are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD.Recent research has yielded promising results,indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function.This minireview outlines the physiological roles of BAs,seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression,and highlights current and emerging therapeutic approa-ches.A deeper understanding of these complex interactions is essential for improving the diagnosis,prognosis and treatment of MASLD.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in patients with type 2 diabetes mellitus(T2DM),is increasingly recognized as a multi-system disease that affects both hepatic and cardiovas...Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in patients with type 2 diabetes mellitus(T2DM),is increasingly recognized as a multi-system disease that affects both hepatic and cardiovascular health.This study explores the association between MASLD-related liver fibrosis and cardiac dysfunction,focusing on how liver fibrosis contributes to cardiac remodeling and dysfunction.Cernea et al’s research highlights the strong correlation between liver fibrosis and changes in left ventricular mass,left atrial dimensions,and systolic and diastolic function in diabetic patients.Notably,the study suggests a protective role of sex-hormone binding protein against cardiac remodeling.These findings underline the importance of early detection of liver fibrosis using noninvasive markers like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores,which may offer dual protection for both liver and heart health in T2DM patients.Moreover,this study calls for further research into the shared pathogenic mechanisms,including inflammation and fibrosis pathways,between the liver and heart.It advocates for the integration of liver fibrosis screening into cardiovascular risk management,urging clinicians to adopt a more holistic approach in treating patients with MASLD and T2DM.The research has broad implications for preventing cardiovascular complications and improving outcomes in this highrisk population.展开更多
Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male m...Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.展开更多
Neurodegenerative diseases are chronic,age-related disorders characterized by a relentless,irreversible,and selective loss of neurons in motor,sensory,or cognitive systems(Gao et al.,2019).Despite their heterogeneity,...Neurodegenerative diseases are chronic,age-related disorders characterized by a relentless,irreversible,and selective loss of neurons in motor,sensory,or cognitive systems(Gao et al.,2019).Despite their heterogeneity,a common pathological feature across many of these diseases is the accumulation of aggregate-prone proteins.Particularly,the cytoplasmic aggregation in neurons of the Transactive response DNA-binding protein 43(TDP-43).展开更多
The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiologic...The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)i...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage.展开更多
The worldwide epidemiology of non-alcoholic fatty liver disease(NAFLD)is showing an upward trend,parallel to the rising trend of metabolic syndrome,owing to lifestyle changes.The pathogenesis of NAFLD has not been ful...The worldwide epidemiology of non-alcoholic fatty liver disease(NAFLD)is showing an upward trend,parallel to the rising trend of metabolic syndrome,owing to lifestyle changes.The pathogenesis of NAFLD has not been fully understood yet.Therefore,NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide.Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication.Lifestyle changes are the main treatment modality.Recently,clinical trial using drugs that target‘insulin resistance’which is the driving force behind NAFLD,have shown promising results.Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets.The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively.Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in the presence of liver fibrosis,increases the risk of cardiovascular morbidity and mortality,but the nature of the cardio-hepat...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in the presence of liver fibrosis,increases the risk of cardiovascular morbidity and mortality,but the nature of the cardio-hepatic interaction in the context type 2 diabetes mellitus(T2DM)is not fully understood.AIM To evaluate the changes in cardiac morphology and function in patients with T2DM and MASLD-associated liver fibrosis.METHODS T2DM patients with MASLD underwent a medical evaluation that included an assessment of lifestyle,anthropometric measurements,vital signs,an extensive laboratory panel,and a standard echocardiography.Liver fibrosis was evaluated using two scores[Fibrosis-4(FIB4)and Non-alcoholic fatty liver disease-Fibrosis Score(NFS)],and subjects were classified as having advanced fibrosis,no fibrosis,or an indeterminate risk.The correlations between structural and functional cardiac parameters and markers of liver fibrosis were evaluated through bivariate and multiple regression analyses.Statistical significance was set at P<0.05.RESULTS Data from 267 T2DM-MASLD subjects with complete assessment was analyzed.Patients with scores indicating advanced fibrosis exhibited higher interventricular septum and left ventricular(LV)posterior wall thickness,atrial diameters,LV end-systolic volume,LV mass index(LVMi),and epicardial adipose tissue thickness(EATT).Their mean ejection fraction(EF)was significantly lower(49.19%±5.62%vs 50.87%±5.14%vs 52.00%±3.25%;P=0.003),and a smaller proportion had an EF≥50%(49.40%vs 68.90%vs 84.21%;P=0.0017).Their total and mid LV wall motion score indexes were higher(P<0.05).Additionally,they had markers of diastolic dysfunction,with a higher E/e’ratio[9.64±4.10 vs 8.44(2.43-26.33)vs 7.35±2.62;P=0.026],and over 70%had lateral e’values<10 cm/second,though without significant differences between groups.In multiple regression analyses,FIB4 correlated with left atrium diameter(LAD;β=0.044;P<0.05),and NFS with both LAD(β=0.039;P<0.05)and right atrium diameter(β=0.041;P<0.01),Moreover,LVMi correlated positively with age and EATT(β=1.997;P=0.0008),and negatively with serum sex-hormone binding protein(SHBP)concentrations(β=-0.280;P=0.004).SHBP also correlated negatively with LAD(β=-0.036;P<0.05).CONCLUSION T2DM patients with markers of MASLD-related liver fibrosis exhibit lower EF and present indicators of diastolic dysfunction and cardiac hypertrophy.Additionally,LVMi and LAD correlated negatively with serum SHBP concentrations.展开更多
Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver diseas...Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.展开更多
The majority of our daily activities and routines are highly dependent on vision.What we experience as our vision arises from the detection and encoding of visual signals in the retina,which are then interpreted in th...The majority of our daily activities and routines are highly dependent on vision.What we experience as our vision arises from the detection and encoding of visual signals in the retina,which are then interpreted in the brain.This interpretation has the benefit of providing a level of constancy to what we experience as vision but also limits our ability to perceive subtle decline in our own vision.展开更多
Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD ...Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD is an important risk factor for cardiovascular and cerebrovascular diseases,including coronary heart disease,stroke,and tumors,with no specific therapeutic drugs currently available.The ethanol extract of cassia seed(CSEE)has shown promise in lowering blood lipids and improving hepatic steatosis,but its mechanism in treating MASLD remains underexplored.This study aims to investigate the therapeutic effects and mechanisms of CSEE.Methods:MASLD models were established in male Wistar rats and golden hamsters using a high fat diet(HFD).CSEE(10,50,250 mg/kg)was administered via gavage for six weeks.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),as well as liver TC and TG,were measured using biochemical kits.Histopathological changes in the liver were evaluated using Oil Red O staining,Hematoxylin-eosin(H&E)staining,and transmission electron microscopy(TEM).HepG2 cell viability was assessed using the cell counting kit-8(CCK8)and Calcein-AM/PI staining.Network pharmacology was used to analyze drug-disease targets,and western blotting was used to confirm these predictions.Results:CSEE treatment significantly reduced serum levels of TC,TG,LDL-C,ALT,and AST,and improved liver weight,liver index,and hepatic lipid deposition in rats and golden hamsters.In addition,CSEE alleviated free fatty acid(FFA)-induced lipid deposition in HepG2 cells.Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK,p-ACC,PPARα,CPT1A,PI3K P110 and p-AKT,while decreasing the protein levels of SREBP1,FASN,C/EBPα,and PPARγ,thus improving hepatic lipid metabolism and reducing lipid deposition.The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro.Conclusion:CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK,PPARα,and PI3K/AKT signaling pathways.展开更多
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 en...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.展开更多
In recent years, non-alcoholic fatty liver disease (NAFLD) has developed rapidly worldwide and has become the main cause of chronic liver disease. With the increase in prevalence, the incidence of NAFLD-related hepato...In recent years, non-alcoholic fatty liver disease (NAFLD) has developed rapidly worldwide and has become the main cause of chronic liver disease. With the increase in prevalence, the incidence of NAFLD-related hepatocellular carcinoma (HCC) has increased sharply. These patients are often diagnosed late, have a poor prognosis, and there is still a lack of corresponding intervention measures. The close connection between NAFLD and metabolic comorbidities has given rise to a new name, “Metabolic dysfunction-associated steatotic liver disease” (MASLD), which provides us with new intervention ideas to curb the progression of liver disease through the common intrinsic mechanisms related to regulating metabolic conditions through multidisciplinary combined treatment of early metabolic comorbidities. This review analyzes the clinical status of NAFLD/MASLD and the intrinsic relationship with related metabolic syndrome, explores the potentially beneficial interventions for MASLD and related HCC in multidisciplinary treatment, including some commonly used clinical drugs, deepens the understanding of the disease and provides references for prevention and intervention.展开更多
文摘Introduction:Advances in HIV management have transformed HIV into a chronic condition,resulting in improved prognosis and increased survival among people living with HIV(PLWH).Traditional risk factors for metabolic dysfunction-associated steatotic liver disease(MASLD)—including dyslipidemia—are prevalent in PLWH.This systematic review and meta-analysis aim to synthesize current evidence on lipid profile disturbances as contributors to MASLD in PLWH.Methods:This systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines and registered in PROSPERO with registration number CRD420251054477.We searched seven databases to identify studies reporting the prevalence and characteristics of MASLD in PLWH.Meta-analysis was conducted using Review Manager 5.4.1.Mean differences(MDs)were calculated using a random-effects model.Risk of bias was assessed using the ROBINS-E tool.Results:A total of 17 studies comprising 3933 HIV-positive participants were included,among whom 1226(37%)had MASLD.Male sex was significantly associated with MASLD(OR=1.57;95%CI:1.13-2.17;p=0.007).MASLD was significantly associated with higher body mass index(BMI)(MD=3.23 kg/m^(2);p<0.00001).Lipid profile analysis revealed that MASLD patients had higher total cholesterol(MD=6.62 mg/dL;p=0.01),low density lipoprotein(LDL)(MD=3.83 mg/dL;p=0.01),triglycerides(MD=63.02 mg/dL;p<0.00001),and lower high density lipoprotein(HDL)(MD=-3.73 mg/dL;p<0.0001).Conclusion:This study demonstrates a significant difference in lipid profiles(higher total cholesterol,LDL,triglycerides,and lower HDL)among PLWH who develop MASLD,suggesting a potential metabolic signature associated with this comorbidity.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.
基金funded by the Program of China Scholarships Council(No.202206785007)“Four New”Experimental Teaching Curriculum Reform Project of Jinan University in China(SYJG202235),the Teaching QualityTeaching Reform Project of Undergraduate University of Guangdong in China(2020).
文摘MASLD in China:an under-recognized public health problem Epidemic characteristics of metabolic dysfunction-associated steatotic liver disease(MASLD)in China As one of the most common chronic non-infectious liver diseases,metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),affects one quarter of the world’s population,is closely related to diabetes and obesity[1,2].
文摘This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.
基金Supported by Russian Science Foundation,No.23-45-10030.
文摘Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological interventions,thereby negatively affecting the prognosis.This review discusses the clinical problems associated with increased fatigue,explores diagnostic methods,considers key pathogenetic mechanisms of this symptom development(including neuroinflammation,hyperammonemia,mitochondrial and muscle dysfunction,sleep disorders,changes in the composition of gut microbiota),and describes the role of interorgan communication(the liver-brain and gut-brain axes)in the formation of the central link of fatigue.The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue,which would include not only the impact on metabolic disorders,but also on neurophysiological and behavioral factors.Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention(which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy)and improve the prognosis of patients with this chronic liver disease.
文摘In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two major contributors to the global burden of liver disease.By analyzing clinical characteristics,metabolic parameters,immune profiles,and liver pathology,Zhao et al comprehensively explored how MASLD influences the presentation,severity,and prognosis of DILI.Additionally,this study underscores the importance of structured diagnostic tools,such as the Roussel Uclaf Causality Assessment Method,to accurately assess the causality of DILI within the MASLD population.Although this study provides valuable insights,limitations such as its retrospective design and cohort heterogeneity underscore the need for future prospective research to refine diagnostic approaches and therapeutic strategies.
文摘Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus(T2DM)and also in those with metabolic dysfunction-associated steatotic liver disease(MASLD).In this editorial,we comment on the results of a meta-analysis published by Shetty et al that shows an addictive risk for cardi-ovascular events when both pathologies are together.Patients with MASLD and T2DM have the worst prognosis related to liver disease since they have a higher risk for metabolic dysfunction-associated steatohepatitis,disease progression,and hepatocarcinoma.The meta-analysis included 370013 participants and showed that,although with high heterogeneity,there is a higher prevalence of cardio-vascular events in patients with T2DM when MASLD is diagnosed compared to those without MASLD.Hence,MASLD and T2DM may have a new interplay regarding cardiovascular outcomes in addition to the already known liver-related outcomes.
文摘The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized from cholesterol in hepatocytes,not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor(FXR)and Takeda G-protein-coupled receptor 5.Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally,closely linked with obesity,insulin resis-tance,and other components of metabolic syndrome.In MASLD,the metabolism of BAs is markedly disrupted,resulting in alterations in their synthesis,compo-sition,and signaling activity.These changes contribute to hepatic steatosis,inflammation,and fibrosis,thereby exacerbating metabolic dysfunction and liver damage.The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity,but also as active mediators of its pathogenesis.Modulators of BA signaling pathways,especially FXR agonists,are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD.Recent research has yielded promising results,indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function.This minireview outlines the physiological roles of BAs,seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression,and highlights current and emerging therapeutic approa-ches.A deeper understanding of these complex interactions is essential for improving the diagnosis,prognosis and treatment of MASLD.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in patients with type 2 diabetes mellitus(T2DM),is increasingly recognized as a multi-system disease that affects both hepatic and cardiovascular health.This study explores the association between MASLD-related liver fibrosis and cardiac dysfunction,focusing on how liver fibrosis contributes to cardiac remodeling and dysfunction.Cernea et al’s research highlights the strong correlation between liver fibrosis and changes in left ventricular mass,left atrial dimensions,and systolic and diastolic function in diabetic patients.Notably,the study suggests a protective role of sex-hormone binding protein against cardiac remodeling.These findings underline the importance of early detection of liver fibrosis using noninvasive markers like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores,which may offer dual protection for both liver and heart health in T2DM patients.Moreover,this study calls for further research into the shared pathogenic mechanisms,including inflammation and fibrosis pathways,between the liver and heart.It advocates for the integration of liver fibrosis screening into cardiovascular risk management,urging clinicians to adopt a more holistic approach in treating patients with MASLD and T2DM.The research has broad implications for preventing cardiovascular complications and improving outcomes in this highrisk population.
基金National Key Research and Development Program of China,Grant/Award Number:2021YFF0702200Science and Technology Projects in Guangzhou,Grant/Award Number:202206010084,202206010197 and 202206060002+1 种基金Guangdong S&T programme,Grant/Award Number:2009A081000002 and 2023B0303040004Technology Planning Project of Linzhi,Grant/Award Number:2023-YZ-01。
文摘Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.
基金funded by the“Instituto de Salud Carlos III”(PI 17-000134,PI 20-0155,PI23/00176)the“Diputaciode Lleida”(PP10601-PIRS2021)to MPO+2 种基金Also from the“Diputaciode Lleida”(PP10605-PIRS2021)the“Generalitat de Catalunya”:Agency for Management of University and Research Grants(2021SGR00990)to RPSupport was also received in the form of a FUNDELA Grant,“RedELA-Plataforma Investigacion”and the“Fundacio Miquel Valls”(Jack Van den Hoek donation)(to MPO)。
文摘Neurodegenerative diseases are chronic,age-related disorders characterized by a relentless,irreversible,and selective loss of neurons in motor,sensory,or cognitive systems(Gao et al.,2019).Despite their heterogeneity,a common pathological feature across many of these diseases is the accumulation of aggregate-prone proteins.Particularly,the cytoplasmic aggregation in neurons of the Transactive response DNA-binding protein 43(TDP-43).
文摘The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.
基金Supported by University of Edinburgh Hepatology Laboratory Internal Fundingthe Liver Endowment Funds of the Edinburgh&Lothian Health Foundation.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage.
文摘The worldwide epidemiology of non-alcoholic fatty liver disease(NAFLD)is showing an upward trend,parallel to the rising trend of metabolic syndrome,owing to lifestyle changes.The pathogenesis of NAFLD has not been fully understood yet.Therefore,NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide.Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication.Lifestyle changes are the main treatment modality.Recently,clinical trial using drugs that target‘insulin resistance’which is the driving force behind NAFLD,have shown promising results.Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets.The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively.Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.
基金Supported by the University of Medicine,Pharmacy,Science and Technology“George Emil Palade”of Târgu MureșResearch Grant,No.10126/5/17.12.2020.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in the presence of liver fibrosis,increases the risk of cardiovascular morbidity and mortality,but the nature of the cardio-hepatic interaction in the context type 2 diabetes mellitus(T2DM)is not fully understood.AIM To evaluate the changes in cardiac morphology and function in patients with T2DM and MASLD-associated liver fibrosis.METHODS T2DM patients with MASLD underwent a medical evaluation that included an assessment of lifestyle,anthropometric measurements,vital signs,an extensive laboratory panel,and a standard echocardiography.Liver fibrosis was evaluated using two scores[Fibrosis-4(FIB4)and Non-alcoholic fatty liver disease-Fibrosis Score(NFS)],and subjects were classified as having advanced fibrosis,no fibrosis,or an indeterminate risk.The correlations between structural and functional cardiac parameters and markers of liver fibrosis were evaluated through bivariate and multiple regression analyses.Statistical significance was set at P<0.05.RESULTS Data from 267 T2DM-MASLD subjects with complete assessment was analyzed.Patients with scores indicating advanced fibrosis exhibited higher interventricular septum and left ventricular(LV)posterior wall thickness,atrial diameters,LV end-systolic volume,LV mass index(LVMi),and epicardial adipose tissue thickness(EATT).Their mean ejection fraction(EF)was significantly lower(49.19%±5.62%vs 50.87%±5.14%vs 52.00%±3.25%;P=0.003),and a smaller proportion had an EF≥50%(49.40%vs 68.90%vs 84.21%;P=0.0017).Their total and mid LV wall motion score indexes were higher(P<0.05).Additionally,they had markers of diastolic dysfunction,with a higher E/e’ratio[9.64±4.10 vs 8.44(2.43-26.33)vs 7.35±2.62;P=0.026],and over 70%had lateral e’values<10 cm/second,though without significant differences between groups.In multiple regression analyses,FIB4 correlated with left atrium diameter(LAD;β=0.044;P<0.05),and NFS with both LAD(β=0.039;P<0.05)and right atrium diameter(β=0.041;P<0.01),Moreover,LVMi correlated positively with age and EATT(β=1.997;P=0.0008),and negatively with serum sex-hormone binding protein(SHBP)concentrations(β=-0.280;P=0.004).SHBP also correlated negatively with LAD(β=-0.036;P<0.05).CONCLUSION T2DM patients with markers of MASLD-related liver fibrosis exhibit lower EF and present indicators of diastolic dysfunction and cardiac hypertrophy.Additionally,LVMi and LAD correlated negatively with serum SHBP concentrations.
文摘Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.
基金supported by Vetenskapsrådet 2022-00799 and the Ulla and Ingemar Dahlberg Foundation(to PAW).
文摘The majority of our daily activities and routines are highly dependent on vision.What we experience as our vision arises from the detection and encoding of visual signals in the retina,which are then interpreted in the brain.This interpretation has the benefit of providing a level of constancy to what we experience as vision but also limits our ability to perceive subtle decline in our own vision.
基金The animal protocols were approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University(SYDW2019-258).
文摘Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD is an important risk factor for cardiovascular and cerebrovascular diseases,including coronary heart disease,stroke,and tumors,with no specific therapeutic drugs currently available.The ethanol extract of cassia seed(CSEE)has shown promise in lowering blood lipids and improving hepatic steatosis,but its mechanism in treating MASLD remains underexplored.This study aims to investigate the therapeutic effects and mechanisms of CSEE.Methods:MASLD models were established in male Wistar rats and golden hamsters using a high fat diet(HFD).CSEE(10,50,250 mg/kg)was administered via gavage for six weeks.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),as well as liver TC and TG,were measured using biochemical kits.Histopathological changes in the liver were evaluated using Oil Red O staining,Hematoxylin-eosin(H&E)staining,and transmission electron microscopy(TEM).HepG2 cell viability was assessed using the cell counting kit-8(CCK8)and Calcein-AM/PI staining.Network pharmacology was used to analyze drug-disease targets,and western blotting was used to confirm these predictions.Results:CSEE treatment significantly reduced serum levels of TC,TG,LDL-C,ALT,and AST,and improved liver weight,liver index,and hepatic lipid deposition in rats and golden hamsters.In addition,CSEE alleviated free fatty acid(FFA)-induced lipid deposition in HepG2 cells.Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK,p-ACC,PPARα,CPT1A,PI3K P110 and p-AKT,while decreasing the protein levels of SREBP1,FASN,C/EBPα,and PPARγ,thus improving hepatic lipid metabolism and reducing lipid deposition.The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro.Conclusion:CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK,PPARα,and PI3K/AKT signaling pathways.
文摘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.
文摘In recent years, non-alcoholic fatty liver disease (NAFLD) has developed rapidly worldwide and has become the main cause of chronic liver disease. With the increase in prevalence, the incidence of NAFLD-related hepatocellular carcinoma (HCC) has increased sharply. These patients are often diagnosed late, have a poor prognosis, and there is still a lack of corresponding intervention measures. The close connection between NAFLD and metabolic comorbidities has given rise to a new name, “Metabolic dysfunction-associated steatotic liver disease” (MASLD), which provides us with new intervention ideas to curb the progression of liver disease through the common intrinsic mechanisms related to regulating metabolic conditions through multidisciplinary combined treatment of early metabolic comorbidities. This review analyzes the clinical status of NAFLD/MASLD and the intrinsic relationship with related metabolic syndrome, explores the potentially beneficial interventions for MASLD and related HCC in multidisciplinary treatment, including some commonly used clinical drugs, deepens the understanding of the disease and provides references for prevention and intervention.
