Bariatric and metabolic surgeries have gained extensive popularity and trust due to their documented efficacy and safety in managing not only obesity but also associated comorbidities such as diabetes mellitus, hypert...Bariatric and metabolic surgeries have gained extensive popularity and trust due to their documented efficacy and safety in managing not only obesity but also associated comorbidities such as diabetes mellitus, hypertension, dyslipidemia, sleep apnea, and joint pain. Traditionally, bariatric surgeries have been categorized into hypoabsorptive, restrictive, or hybrid approaches. However, these classifications inadequately reflect the complex anatomical and physiological alterations associated with modern surgical methodologies. This paper explores the evolution of metabolic surgeries, emphasizing the integration of physiological concepts into classic procedures to provide more tailored and effective treatment options for obesity and its comorbidities. Finally, the proposal for a new classification based on current metabolic concepts will facilitate communication among patients, doctors, and healthcare professionals. Additionally, it will enable a more didactic and standardized approach to data collection for conducting studies and publications.展开更多
Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness ...Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.展开更多
This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal o...This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal of Gastroenterology.The study explores the therapeutic potential of Fanlian Huazhuo formula(FLHZF)in treating metabolic-associated steatotic liver disease(MASLD),demonstrating that FLHZF reduces lipid accumulation,oxidative stress,and liver injury in MASLD models by modulating key signaling pathways involved in lipid metabolism and autophagy.This editorial emphasizes the potential of FLHZF as a treatment for MASLD and calls for further research to verify its clinical efficacy.展开更多
Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Na...Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.展开更多
BACKGROUND At present,the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent,to explore the efficacy of laparoscopic jejunoileal side to side anastomosis ...BACKGROUND At present,the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent,to explore the efficacy of laparoscopic jejunoileal side to side anastomosis in the treatment of type 2 diabetes,the report is as follows.AIM To investigate the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes mellitus(T2DM).METHODS We retrospectively analyzed the clinical data of 78 patients with T2DM who were treated via jejunoileal lateral anastomosis.Metabolic indicators were collected preoperatively,as well as at 3 and 6 months postoperative.The metabolic indicators analyzed included body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting blood glucose(FBG),2-hour blood glucose(PBG),glycated hemoglobin(HbA1c),fasting C-peptide,2-hour C-peptide(PCP),fasting insulin(Fins),2-hour insulin(Pins),insulin resistance index(HOMA-IR),βCellular function index(HOMA-β),alanine aminotransferase,aspartate aminotransferase,serum total cholesterol(TC),low-density lipoprotein cholesterol(L DL-C),triglycerides(TG),high-density lipoprotein,and uric acid(UA)levels.RESULTS SBP,DBP,PBG,HbA1c,LDL-C,and TG were all significantly lower 3 months postoperative vs preoperative values;body weight,BMI,SBP,DBP,FBG,PBG,HbA1c,TC,TG,UA,and HOMA-IR values were all significantly lower 6 months postoperative vs at 3 months;and PCP,Fins,Pins,and HOMA-βwere all significantly higher 6 months postoperative vs at 3 months(all P<0.05).CONCLUSION Side-to-side anastomosis of the jejunum and ileum can effectively treat T2DM and improve the metabolic index levels associated with it.展开更多
This editorial comments on the study by Pierzynowska et al investigating the acini-islet-acinar(AIA)reflex,which integrates the exocrine and endocrine functions of the pancreas.The study investigates whether exogenous...This editorial comments on the study by Pierzynowska et al investigating the acini-islet-acinar(AIA)reflex,which integrates the exocrine and endocrine functions of the pancreas.The study investigates whether exogenous amylase introduced to the interstitial fluid surrounding pancreatic islets can inhibit insulin release.Historically,high serum amylase levels were associated with pancreatitis,but recent findings suggest that low amylase levels are more linked to metabolic diseases like diabetes and obesity.In their experiment,six pigs were used to examine the effects of amylase infusion on insulin release during an intravenous glucose tolerance test.The pigs received different treatments(amylase,saline,or bovine serum albumin),and blood samples were taken over two hours to measure insulin and glucose levels.The results showed amylase delayed glucose-stimulated insulin release,whereas bovine serum albumin increased insulin levels supporting the existence of the AIA reflex and suggesting amylase as a key metabolic regulator.Enzyme supplementation,particularly withα-amylases,may offer therapeutic benefits in preventing and managing metabolic disorders,including diabetes and obesity.Further research is warranted to explore the full scope of amylase’s role in metabolic health and its therapeutic potential.展开更多
BACKGROUND Chronic hepatitis B(CHB)affects>300 million people worldwide.The combi-nation of CHB and cardiometabolic co-morbidities increases the risk of liver-related morbidity and mortality.However,international g...BACKGROUND Chronic hepatitis B(CHB)affects>300 million people worldwide.The combi-nation of CHB and cardiometabolic co-morbidities increases the risk of liver-related morbidity and mortality.However,international guidelines for CHB treatment do not provide recommendations for follow-up examinations or treatment of patients with CHB and cardiometabolic comorbidities.In studies investigating cardiometabolic co-morbidity in patients with CHB,inconsistent findings have been observed,and both lower and higher prevalence of car-diometabolic co-morbidities compared to the general population have been re-ported.It is unclear whether patients with CHB living in Denmark have an increased prevalence of cardiometabolic co-morbidities.We examined patients with CHB and age-,sex-,body mass index(BMI)-,and country-of-birth matched comparison group.Defining cardiometabolic co-morbidity:Obesity(BMI>25 kg/m2/abnormal waist-to-hip ratio),metabolic dysfunction-associated steatotic liver disease(MASLD),hypercholesterolemia(total-cholesterol>5 mmol/L/statin use),hypertension(systolic≥135 mmHg/diastolic≥85 mmHg/antihypertensive medication)and type 2 diabetes(T2D)(2-hour oral glucose tolerance test glucose>11.1 mmol/L/HbA1c>48 mmol/mol/antidiabetic medication).Physical activity was evaluated using maximal oxygen consumption(VO2max),activity monitors,and a questionnaire.RESULTS We included 98 patients with CHB and 49 persons in the comparison group.The two groups were well-matched,showing no significant differences in age,sex,BMI,country-of-birth,education,or employment.Among patients with CHB,the following prevalence of cardiometabolic co-morbidity was found:77%were obese,45%had MASLD,38%had hypercholesterolemia,26%had hypertension,and 7%had T2D,which did not differ significantly from the comparison group,apart from lower prevalence of hemoglobin A1c(HbA1c)≥48 mmol/L or known T2D.Both groups had low VO2max of 27 mL/kg/minute in the patients with CHB and 30 mL/kg/minute in the comparison group,and the patients with CHB had a shorter self-assessed sitting time.CONCLUSION The patients with CHB and the comparison group were well-matched and had a similar prevalence of car-diometabolic comorbidities.Furthermore,both groups had low levels of physical fitness.展开更多
This letter discusses the research conducted by Abdel-Razeq et al,highlighting a significant association between Helicobacter pylori(H.pylori)infection and me-tabolic dysfunction-associated steatohepatitis(MASH)in ind...This letter discusses the research conducted by Abdel-Razeq et al,highlighting a significant association between Helicobacter pylori(H.pylori)infection and me-tabolic dysfunction-associated steatohepatitis(MASH)in individuals with a prior history of H.pylori infection.Using a comprehensive patient database,the study establishes an independent correlation between H.pylori and an elevated risk of MASH,even after adjusting for coexisting conditions such as obesity,type 2 diabetes,and dyslipidemia.Notably,the findings suggest that H.pylori may wo-rsen liver pathology through inflammatory pathways,contributing to hepatic insulin resistance and lipid accumulation.Although the study provides strong evidence for this association,limitations related to diagnostic heterogeneity in-dicate a need for further research to clarify the underlying mechanisms and to explore the potential roles of genetic and microbiome factors in this relationship.展开更多
BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in the...BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.展开更多
We are deeply interested in the recent findings onβ-arrestin 2.Liu et al demonstrated thatβ-arrestin 2 knockout provides significant protection in diabetic nephropathy,underscoring its potential as a promising thera...We are deeply interested in the recent findings onβ-arrestin 2.Liu et al demonstrated thatβ-arrestin 2 knockout provides significant protection in diabetic nephropathy,underscoring its potential as a promising therapeutic target for diabetic nephropathy treatment.Furthermore,the role ofβ-arrestin 2 in metabolic regulation is equally critical,particularly in insulin signaling,hepatic glucose production,and adipose tissue function.Althoughβ-arrestin 2 plays a distinct role in metabolism and kidney protection,its tissue-specific regulation opens up valuable avenues for developing targeted therapeutic strategies centered onβ-arrestin 2.展开更多
Due to sedentary lifestyle and rising prevalence of obesity,patients with general population and those who are infected with chronic hepatitis B are found to have metabolic dysfunction associated steatotic liver disea...Due to sedentary lifestyle and rising prevalence of obesity,patients with general population and those who are infected with chronic hepatitis B are found to have metabolic dysfunction associated steatotic liver disease(MASLD).Both chronic hepatitis B virus(HBV)infection and MASLD can damage hepatocytes in their own way,but concomitant HBV-MASLD has its own clinical implications.Cherry on top is the presence of diabetes mellitus,hypertension or obesity which added more chances of unfavorable outcomes in these patients.In this article,we co-mment on the article by Wang et al published in the recent issue.This article provides a comprehensive overview of the complex interaction between HBV-MASLD,HBV alone and MASLD alone patients.We discuss key findings from recent studies,including the promising outcomes observed in patients with concurrent HBV and MASLD,warrants further research.The insights presented here offer renewed understanding of this complex interaction.展开更多
Background AflatoxinB1(AFB_(1))is a prevalent contaminant in agricultural products,presenting significant risks to animal health.CotA laccase from Bacillus licheniformis has shown significant efficacy in degrading myc...Background AflatoxinB1(AFB_(1))is a prevalent contaminant in agricultural products,presenting significant risks to animal health.CotA laccase from Bacillus licheniformis has shown significant efficacy in degrading mycotoxins in vitro test.The efficacy of Bacillus CotA laccase in animals,however,remains to be confirmed.A 2×2 factorial design was used to investigate the effects of Bacillus CotA laccase level(0 or 1 U/kg),AFB_(1) challenge(challenged or unchal-lenged)and their interactions on ducks.The purpose of this study was to evaluate the efficacy of Bacillus CotA laccase in alleviatingAFB_(1) toxicosis of ducks.Results Bacillus CotA laccase alleviatedAFB_(1)-induced declines in growth performance of ducks accompanied by improved average daily gain(ADG)and lower feed/gain ratio(F/G).Bacillus CotA laccase amelioratedAFB_(1)-induced gut barrier dysfunctions and inflammation testified by increasing the jejunal villi height/crypt depth ratio(VH/CD)and the mRNA expression of tight junction protein 1(TJP1)and zonula occluden-1(ZO-1)as well as decreasing the expression of inflammation-related genes in the jejunum of ducks.Amino acid metabolome showed that Bacillus CotA laccase amelioratedAFB_(1)-induced amino acid metabolism disorders evidenced by increasing the level of glu-tamic acid in serum and upregulating the expression of amino acid transport related genes in jejunum of ducks.Bacil-lus CotA laccase amelioratedAFB_(1)-induced liver injury testified by suppressing oxidative stress,inhibiting apoptosis,and downregulating the expression of hepatic metabolic enzyme related genes of ducks.Moreover,Bacillus CotA laccase degradedAFB_(1) in digestive tract of ducks,resulting in the reduced absorption level ofAFB_(1) across intestinal epithelium testified by the decreased level ofAFB_(1)-DNA adduct in the liver,and the reduced content ofAFB_(1) residues in liver and feces of ducks.Conclusions Bacillus CotA laccase effectively improved the growth performance,intestinal health,amino acid metabolism and hepatic aflatoxin metabolism of ducks fedAFB_(1) diets,highlighting its potential as an efficient and safe feed enzyme forAFB_(1) degradation in animal production.展开更多
Helicobacter pylori(H.pylori)infection is a known inducer of various gastroin-testinal diseases,including gastritis,gastric ulcers,and gastric cancer.However,in recent years,research on the potential association betwe...Helicobacter pylori(H.pylori)infection is a known inducer of various gastroin-testinal diseases,including gastritis,gastric ulcers,and gastric cancer.However,in recent years,research on the potential association between H.pylori infection and metabolic dysfunction-associated steatohepatitis(MASH)has been scarce.This large-scale multicenter study,covering more than 360 hospitals across 26 medical systems in the United States,systematically evaluated the association between H.pylori infection and MASH.This paper reviews the innovative aspects of this study,discusses its significance in the current research field of H.pylori and liver diseases,analyzes potential molecular mechanisms,and suggests future research directions and therapeutic prospects.展开更多
BACKGROUND Kidney dysfunction and reduced filtration capacity due to chronic kidney disease(CKD)lead to a shift in the body's acid-base balance,ultimately causing metabolic acidosis(MA).Sodium bicarbonate has been...BACKGROUND Kidney dysfunction and reduced filtration capacity due to chronic kidney disease(CKD)lead to a shift in the body's acid-base balance,ultimately causing metabolic acidosis(MA).Sodium bicarbonate has been used as a supplement to alleviate the symptoms and reverse the acidosis,and it may even slow the progression of CKD.However,its safety profile and overall effectiveness are uncertain.AIM To conduct a systematic review and meta-analysis of clinical trials assessing sodium bicarbonate's safety and efficacy for treating CKD-induced MA.METHODS Medline,Scopus,EMBASE,and Cochrane Central were systematically searched from inception until May 2024 to select all relevant randomized control trials(RCTs)and non-RCT(NRCTs)evaluating the effectiveness of sodium bicarbonate in correcting MA in end-stage renal disease patients.In addition,ClinicalTrials.gov,Medrxiv.org,and Google Scholar were searched for other literature.A random-effects meta-analysis was performed to derive mean differences(MD)and risk ratios(RR)with their 95%CI for continuous and dichotomous outcomes respectively.RESULTS Following a systematic search of the databases,20 RCTs and 2 and NRCTs comprising 2932 patients were included in our study.The results revealed that sodium bicarbonate significantly increased serum bicarbonate in CKD patients(MD:2.59,95%CI:0.95-4.22;P=0.02;I2=95%).However,there was a non-significant increase in estimated glomerular filtration rate(eGFR)in patients on sodium bicarbonate therapy(MD:0.93,95%CI:-1.88-3.75;P=0.52;I2=93%).Upon assessment of the safety profile of sodium bicarbonate,no significant association was found in the outcomes of death/prolonged hospitalization(RR:1.05,95%CI:0.84-1.32;P=0.66;I2=0%),or gastrointestinal disorders(RR:1.64,95%CI:0.35-7.66;P=0.53;I2=76%),or worsening edema(RR:1.26,95%CI:0.94-1.68;P=0.12;I2=37%)when compared to control.CONCLUSION Sodium bicarbonate therapy may halt worsening kidney function by correcting serum bicarbonate levels and treating MA.Although sodium bicarbonate does not significantly improve the eGFR,it may potentially prevent CKD progression while maintaining an overall favorable safety profile.展开更多
This letter discusses the recent study by Mukherjee et al,which identifies a significant prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)among newly diagnosed type 2 diabetes mellitus(T2DM...This letter discusses the recent study by Mukherjee et al,which identifies a significant prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)among newly diagnosed type 2 diabetes mellitus(T2DM)patients in Bihar,India,and underscores the pressing need for integrated MASLD mana-gement within T2DM care.With 72.3%of the study cohort affected by MASLD,implementing routine liver function tests and ultrasound screenings is recom-mended as a standard practice in diabetes care,especially in regions with high prevalence rates.The study also advocates for dietary and lifestyle modifications,particularly the reduction of saturated fats,to slow MASLD progression.Patient education on monitoring body mass index and waist circumference,coupled with the integration of these metrics into digital health records,could enhance patient involvement and support proactive health management.Moreover,the letter emphasizes the advantages of developing a region-specific MASLD risk model that incorporates local dietary patterns and socioeconomic factors.Continued research into genetic and environmental determinants of MASLD remains es-sential for advancing our understanding of its etiology and informing targeted public health strategies.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most count...Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes.Th...Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes.The redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated risks.MASLD is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic inflammation.Diagnostic challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools.Therapeutically,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid metabolism.Additionally,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches.There is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.展开更多
The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given th...The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.展开更多
Qu and Li emphasize a fundamental aspect of metabolic dysfunction-associated fatty liver disease in their manuscript,focusing on the critical need for noninvasive diagnostic tools to improve risk stratification and pr...Qu and Li emphasize a fundamental aspect of metabolic dysfunction-associated fatty liver disease in their manuscript,focusing on the critical need for noninvasive diagnostic tools to improve risk stratification and predict the progression to severe liver complications.Affecting approximately 25%of the global population,metabolic dysfunction-associated fatty liver disease is the most common chronic liver condition,with higher prevalence among those with obesity.This letter stresses the importance of early diagnosis and intervention,especially given the rising incidence of obesity and metabolic syndrome.Research advancements provide insight into the potential of biomarkers(particularly inflammationrelated)as predictive tools for disease progression and treatment response.This overview addresses pleiotropic biomarkers linked to chronic inflammation and cardiometabolic disorders,which may aid in risk stratification and treatment efficacy monitoring.Despite progress,significant knowledge gaps remain in the clinical application of these biomarkers,necessitating further research to establish standardized protocols and validate their utility in clinical practice.Understanding the complex interactions among these factors opens new avenues to enhance risk assessment,leading to better patient outcomes and addressing the public health burden of this worldwide condition.展开更多
Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic...Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.展开更多
文摘Bariatric and metabolic surgeries have gained extensive popularity and trust due to their documented efficacy and safety in managing not only obesity but also associated comorbidities such as diabetes mellitus, hypertension, dyslipidemia, sleep apnea, and joint pain. Traditionally, bariatric surgeries have been categorized into hypoabsorptive, restrictive, or hybrid approaches. However, these classifications inadequately reflect the complex anatomical and physiological alterations associated with modern surgical methodologies. This paper explores the evolution of metabolic surgeries, emphasizing the integration of physiological concepts into classic procedures to provide more tailored and effective treatment options for obesity and its comorbidities. Finally, the proposal for a new classification based on current metabolic concepts will facilitate communication among patients, doctors, and healthcare professionals. Additionally, it will enable a more didactic and standardized approach to data collection for conducting studies and publications.
基金supported by the National Natural Science Foundation of China,No.82202681(to JW)the Natural Science Foundation of Zhejiang Province,Nos.LZ22H090003(to QC),LR23H060001(to CL).
文摘Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.
文摘This article reviews the study,“Fanlian huazhuo formula alleviates high-fat-dietinduced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway”published in the World Journal of Gastroenterology.The study explores the therapeutic potential of Fanlian Huazhuo formula(FLHZF)in treating metabolic-associated steatotic liver disease(MASLD),demonstrating that FLHZF reduces lipid accumulation,oxidative stress,and liver injury in MASLD models by modulating key signaling pathways involved in lipid metabolism and autophagy.This editorial emphasizes the potential of FLHZF as a treatment for MASLD and calls for further research to verify its clinical efficacy.
基金supported by the National Natural Science Foundation of China,No.82101327(to YY)President Foundation of Nanfang Hospital,Southern Medical University,No.2020A001(to WL)+1 种基金Guangdong Basic and Applied Basic Research Foundation,Nos.2019A1515110150,2022A1515012362(both to YY)Guangzhou Science and Technology Project,No.202201020111(to YY).
文摘Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.
文摘BACKGROUND At present,the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent,to explore the efficacy of laparoscopic jejunoileal side to side anastomosis in the treatment of type 2 diabetes,the report is as follows.AIM To investigate the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes mellitus(T2DM).METHODS We retrospectively analyzed the clinical data of 78 patients with T2DM who were treated via jejunoileal lateral anastomosis.Metabolic indicators were collected preoperatively,as well as at 3 and 6 months postoperative.The metabolic indicators analyzed included body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting blood glucose(FBG),2-hour blood glucose(PBG),glycated hemoglobin(HbA1c),fasting C-peptide,2-hour C-peptide(PCP),fasting insulin(Fins),2-hour insulin(Pins),insulin resistance index(HOMA-IR),βCellular function index(HOMA-β),alanine aminotransferase,aspartate aminotransferase,serum total cholesterol(TC),low-density lipoprotein cholesterol(L DL-C),triglycerides(TG),high-density lipoprotein,and uric acid(UA)levels.RESULTS SBP,DBP,PBG,HbA1c,LDL-C,and TG were all significantly lower 3 months postoperative vs preoperative values;body weight,BMI,SBP,DBP,FBG,PBG,HbA1c,TC,TG,UA,and HOMA-IR values were all significantly lower 6 months postoperative vs at 3 months;and PCP,Fins,Pins,and HOMA-βwere all significantly higher 6 months postoperative vs at 3 months(all P<0.05).CONCLUSION Side-to-side anastomosis of the jejunum and ileum can effectively treat T2DM and improve the metabolic index levels associated with it.
基金Supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,No.NRF-RS-2023-00237287,No.NRF-2021S1A5A8062526Local Government-University Cooperation-Based Regional Innovation Projects,No.2021RIS-003.
文摘This editorial comments on the study by Pierzynowska et al investigating the acini-islet-acinar(AIA)reflex,which integrates the exocrine and endocrine functions of the pancreas.The study investigates whether exogenous amylase introduced to the interstitial fluid surrounding pancreatic islets can inhibit insulin release.Historically,high serum amylase levels were associated with pancreatitis,but recent findings suggest that low amylase levels are more linked to metabolic diseases like diabetes and obesity.In their experiment,six pigs were used to examine the effects of amylase infusion on insulin release during an intravenous glucose tolerance test.The pigs received different treatments(amylase,saline,or bovine serum albumin),and blood samples were taken over two hours to measure insulin and glucose levels.The results showed amylase delayed glucose-stimulated insulin release,whereas bovine serum albumin increased insulin levels supporting the existence of the AIA reflex and suggesting amylase as a key metabolic regulator.Enzyme supplementation,particularly withα-amylases,may offer therapeutic benefits in preventing and managing metabolic disorders,including diabetes and obesity.Further research is warranted to explore the full scope of amylase’s role in metabolic health and its therapeutic potential.
基金Supported by The Centre for Physical Activity Research(CFAS),TrygFonden,No.125132and The Beckett Foundation,No.22-2-9924.
文摘BACKGROUND Chronic hepatitis B(CHB)affects>300 million people worldwide.The combi-nation of CHB and cardiometabolic co-morbidities increases the risk of liver-related morbidity and mortality.However,international guidelines for CHB treatment do not provide recommendations for follow-up examinations or treatment of patients with CHB and cardiometabolic comorbidities.In studies investigating cardiometabolic co-morbidity in patients with CHB,inconsistent findings have been observed,and both lower and higher prevalence of car-diometabolic co-morbidities compared to the general population have been re-ported.It is unclear whether patients with CHB living in Denmark have an increased prevalence of cardiometabolic co-morbidities.We examined patients with CHB and age-,sex-,body mass index(BMI)-,and country-of-birth matched comparison group.Defining cardiometabolic co-morbidity:Obesity(BMI>25 kg/m2/abnormal waist-to-hip ratio),metabolic dysfunction-associated steatotic liver disease(MASLD),hypercholesterolemia(total-cholesterol>5 mmol/L/statin use),hypertension(systolic≥135 mmHg/diastolic≥85 mmHg/antihypertensive medication)and type 2 diabetes(T2D)(2-hour oral glucose tolerance test glucose>11.1 mmol/L/HbA1c>48 mmol/mol/antidiabetic medication).Physical activity was evaluated using maximal oxygen consumption(VO2max),activity monitors,and a questionnaire.RESULTS We included 98 patients with CHB and 49 persons in the comparison group.The two groups were well-matched,showing no significant differences in age,sex,BMI,country-of-birth,education,or employment.Among patients with CHB,the following prevalence of cardiometabolic co-morbidity was found:77%were obese,45%had MASLD,38%had hypercholesterolemia,26%had hypertension,and 7%had T2D,which did not differ significantly from the comparison group,apart from lower prevalence of hemoglobin A1c(HbA1c)≥48 mmol/L or known T2D.Both groups had low VO2max of 27 mL/kg/minute in the patients with CHB and 30 mL/kg/minute in the comparison group,and the patients with CHB had a shorter self-assessed sitting time.CONCLUSION The patients with CHB and the comparison group were well-matched and had a similar prevalence of car-diometabolic comorbidities.Furthermore,both groups had low levels of physical fitness.
文摘This letter discusses the research conducted by Abdel-Razeq et al,highlighting a significant association between Helicobacter pylori(H.pylori)infection and me-tabolic dysfunction-associated steatohepatitis(MASH)in individuals with a prior history of H.pylori infection.Using a comprehensive patient database,the study establishes an independent correlation between H.pylori and an elevated risk of MASH,even after adjusting for coexisting conditions such as obesity,type 2 diabetes,and dyslipidemia.Notably,the findings suggest that H.pylori may wo-rsen liver pathology through inflammatory pathways,contributing to hepatic insulin resistance and lipid accumulation.Although the study provides strong evidence for this association,limitations related to diagnostic heterogeneity in-dicate a need for further research to clarify the underlying mechanisms and to explore the potential roles of genetic and microbiome factors in this relationship.
文摘BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.
基金Supported by National Natural Science Foundation of China,No.82471616,No.82170418,and No.82271618Natural Science Foundation of Hubei Province,No.2022CFA015+2 种基金Central Guiding Local Science and Technology Development Project,No.2022BGE237Key Research and Development Program of Hubei Province,No.2022BCE001,and No.2023BCB139Hubei Provincial Health Commission Project,No.WJ2023M151。
文摘We are deeply interested in the recent findings onβ-arrestin 2.Liu et al demonstrated thatβ-arrestin 2 knockout provides significant protection in diabetic nephropathy,underscoring its potential as a promising therapeutic target for diabetic nephropathy treatment.Furthermore,the role ofβ-arrestin 2 in metabolic regulation is equally critical,particularly in insulin signaling,hepatic glucose production,and adipose tissue function.Althoughβ-arrestin 2 plays a distinct role in metabolism and kidney protection,its tissue-specific regulation opens up valuable avenues for developing targeted therapeutic strategies centered onβ-arrestin 2.
文摘Due to sedentary lifestyle and rising prevalence of obesity,patients with general population and those who are infected with chronic hepatitis B are found to have metabolic dysfunction associated steatotic liver disease(MASLD).Both chronic hepatitis B virus(HBV)infection and MASLD can damage hepatocytes in their own way,but concomitant HBV-MASLD has its own clinical implications.Cherry on top is the presence of diabetes mellitus,hypertension or obesity which added more chances of unfavorable outcomes in these patients.In this article,we co-mment on the article by Wang et al published in the recent issue.This article provides a comprehensive overview of the complex interaction between HBV-MASLD,HBV alone and MASLD alone patients.We discuss key findings from recent studies,including the promising outcomes observed in patients with concurrent HBV and MASLD,warrants further research.The insights presented here offer renewed understanding of this complex interaction.
基金National Key Research and Development Program of China(2021YFC2103003)National Natural Science Foundation of China(31972604)+1 种基金Jinan Introductory Innovation Team Project(No.202228037)China Postdoctoral Science Foundation(2023M730998).
文摘Background AflatoxinB1(AFB_(1))is a prevalent contaminant in agricultural products,presenting significant risks to animal health.CotA laccase from Bacillus licheniformis has shown significant efficacy in degrading mycotoxins in vitro test.The efficacy of Bacillus CotA laccase in animals,however,remains to be confirmed.A 2×2 factorial design was used to investigate the effects of Bacillus CotA laccase level(0 or 1 U/kg),AFB_(1) challenge(challenged or unchal-lenged)and their interactions on ducks.The purpose of this study was to evaluate the efficacy of Bacillus CotA laccase in alleviatingAFB_(1) toxicosis of ducks.Results Bacillus CotA laccase alleviatedAFB_(1)-induced declines in growth performance of ducks accompanied by improved average daily gain(ADG)and lower feed/gain ratio(F/G).Bacillus CotA laccase amelioratedAFB_(1)-induced gut barrier dysfunctions and inflammation testified by increasing the jejunal villi height/crypt depth ratio(VH/CD)and the mRNA expression of tight junction protein 1(TJP1)and zonula occluden-1(ZO-1)as well as decreasing the expression of inflammation-related genes in the jejunum of ducks.Amino acid metabolome showed that Bacillus CotA laccase amelioratedAFB_(1)-induced amino acid metabolism disorders evidenced by increasing the level of glu-tamic acid in serum and upregulating the expression of amino acid transport related genes in jejunum of ducks.Bacil-lus CotA laccase amelioratedAFB_(1)-induced liver injury testified by suppressing oxidative stress,inhibiting apoptosis,and downregulating the expression of hepatic metabolic enzyme related genes of ducks.Moreover,Bacillus CotA laccase degradedAFB_(1) in digestive tract of ducks,resulting in the reduced absorption level ofAFB_(1) across intestinal epithelium testified by the decreased level ofAFB_(1)-DNA adduct in the liver,and the reduced content ofAFB_(1) residues in liver and feces of ducks.Conclusions Bacillus CotA laccase effectively improved the growth performance,intestinal health,amino acid metabolism and hepatic aflatoxin metabolism of ducks fedAFB_(1) diets,highlighting its potential as an efficient and safe feed enzyme forAFB_(1) degradation in animal production.
基金Supported by Basic and Clinical Integration Project of Xi’an Jiaotong University,No.YXJLRH2022067.
文摘Helicobacter pylori(H.pylori)infection is a known inducer of various gastroin-testinal diseases,including gastritis,gastric ulcers,and gastric cancer.However,in recent years,research on the potential association between H.pylori infection and metabolic dysfunction-associated steatohepatitis(MASH)has been scarce.This large-scale multicenter study,covering more than 360 hospitals across 26 medical systems in the United States,systematically evaluated the association between H.pylori infection and MASH.This paper reviews the innovative aspects of this study,discusses its significance in the current research field of H.pylori and liver diseases,analyzes potential molecular mechanisms,and suggests future research directions and therapeutic prospects.
文摘BACKGROUND Kidney dysfunction and reduced filtration capacity due to chronic kidney disease(CKD)lead to a shift in the body's acid-base balance,ultimately causing metabolic acidosis(MA).Sodium bicarbonate has been used as a supplement to alleviate the symptoms and reverse the acidosis,and it may even slow the progression of CKD.However,its safety profile and overall effectiveness are uncertain.AIM To conduct a systematic review and meta-analysis of clinical trials assessing sodium bicarbonate's safety and efficacy for treating CKD-induced MA.METHODS Medline,Scopus,EMBASE,and Cochrane Central were systematically searched from inception until May 2024 to select all relevant randomized control trials(RCTs)and non-RCT(NRCTs)evaluating the effectiveness of sodium bicarbonate in correcting MA in end-stage renal disease patients.In addition,ClinicalTrials.gov,Medrxiv.org,and Google Scholar were searched for other literature.A random-effects meta-analysis was performed to derive mean differences(MD)and risk ratios(RR)with their 95%CI for continuous and dichotomous outcomes respectively.RESULTS Following a systematic search of the databases,20 RCTs and 2 and NRCTs comprising 2932 patients were included in our study.The results revealed that sodium bicarbonate significantly increased serum bicarbonate in CKD patients(MD:2.59,95%CI:0.95-4.22;P=0.02;I2=95%).However,there was a non-significant increase in estimated glomerular filtration rate(eGFR)in patients on sodium bicarbonate therapy(MD:0.93,95%CI:-1.88-3.75;P=0.52;I2=93%).Upon assessment of the safety profile of sodium bicarbonate,no significant association was found in the outcomes of death/prolonged hospitalization(RR:1.05,95%CI:0.84-1.32;P=0.66;I2=0%),or gastrointestinal disorders(RR:1.64,95%CI:0.35-7.66;P=0.53;I2=76%),or worsening edema(RR:1.26,95%CI:0.94-1.68;P=0.12;I2=37%)when compared to control.CONCLUSION Sodium bicarbonate therapy may halt worsening kidney function by correcting serum bicarbonate levels and treating MA.Although sodium bicarbonate does not significantly improve the eGFR,it may potentially prevent CKD progression while maintaining an overall favorable safety profile.
文摘This letter discusses the recent study by Mukherjee et al,which identifies a significant prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)among newly diagnosed type 2 diabetes mellitus(T2DM)patients in Bihar,India,and underscores the pressing need for integrated MASLD mana-gement within T2DM care.With 72.3%of the study cohort affected by MASLD,implementing routine liver function tests and ultrasound screenings is recom-mended as a standard practice in diabetes care,especially in regions with high prevalence rates.The study also advocates for dietary and lifestyle modifications,particularly the reduction of saturated fats,to slow MASLD progression.Patient education on monitoring body mass index and waist circumference,coupled with the integration of these metrics into digital health records,could enhance patient involvement and support proactive health management.Moreover,the letter emphasizes the advantages of developing a region-specific MASLD risk model that incorporates local dietary patterns and socioeconomic factors.Continued research into genetic and environmental determinants of MASLD remains es-sential for advancing our understanding of its etiology and informing targeted public health strategies.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes.The redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated risks.MASLD is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic inflammation.Diagnostic challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools.Therapeutically,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid metabolism.Additionally,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches.There is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.
基金supported by a grant from the French Society of Sleep Research and Medicine(to LS)The China Scholarship Council(to HL)The CNRS,INSERM,Claude Bernard University Lyon1(to LS)。
文摘The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.
文摘Qu and Li emphasize a fundamental aspect of metabolic dysfunction-associated fatty liver disease in their manuscript,focusing on the critical need for noninvasive diagnostic tools to improve risk stratification and predict the progression to severe liver complications.Affecting approximately 25%of the global population,metabolic dysfunction-associated fatty liver disease is the most common chronic liver condition,with higher prevalence among those with obesity.This letter stresses the importance of early diagnosis and intervention,especially given the rising incidence of obesity and metabolic syndrome.Research advancements provide insight into the potential of biomarkers(particularly inflammationrelated)as predictive tools for disease progression and treatment response.This overview addresses pleiotropic biomarkers linked to chronic inflammation and cardiometabolic disorders,which may aid in risk stratification and treatment efficacy monitoring.Despite progress,significant knowledge gaps remain in the clinical application of these biomarkers,necessitating further research to establish standardized protocols and validate their utility in clinical practice.Understanding the complex interactions among these factors opens new avenues to enhance risk assessment,leading to better patient outcomes and addressing the public health burden of this worldwide condition.
基金funded by Basic Research Program of Shanghai,No.20JC1412200(to JW)the National Key Research and Development Program of China,No.2020YFA0113000(to RCZ)。
文摘Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.
