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
BACKGROUND The small intestine is known to play a crucial role in the development and remission of diabetes mellitus(DM).However,the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in ...BACKGROUND The small intestine is known to play a crucial role in the development and remission of diabetes mellitus(DM).However,the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood.AIM To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism.METHODS Streptozotocin(STZ)was used to induce DM in Sprague-Dawley(SD)rats at a dose of 60 mg/kg.The rats were then randomly divided into two groups:The mid-small intestine bypass(MSIB)group and the sham group(underwent switch laparotomy).Following a 6-wk recovery period post-surgery,the rats underwent various assessments,including metabolic parameter testing,analysis of liver glycogen levels,measurement of key gluconeogenic enzyme activity,characterization of the gut microbiota composition,evaluation of hormone levels,determination of bile acid concentrations,and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor.RESULTS The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism,along with increased hepatic glycogen content.Furthermore,there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase.Importantly,the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus,Clostridium symbiosum,Ruminococcus gnavus,and Bilophila.Moreover,higher levels of secondary bile acids,such as intestinal lithocholic acid,were observed in this group.Remarkably,the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1(GLP-1)at 6 wk postoperatively,highlighting their potential role in glucose regulation.These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota.CONCLUSION The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats.This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1,resulting in a favorable modulation of glucose homeostasis.展开更多
In this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GLP-1RA)therapy in the management of type 2 diabetes(T2...In this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GLP-1RA)therapy in the management of type 2 diabetes(T2D)associated with obesity.Bariatric surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D,but information on newer GLP-1RAs in these groups is predictably limited.In older individuals(age>65 years),both bariatric surgery and GLP-1RA therapy improve cardiovascular outcomes.Baria-tric surgery is not infrequently associated with post-operative postprandial hypoglycemia,which is not the case with GLP-1RAs and,paradoxically,there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial hypoglycemia.Comparative trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.展开更多
Liver cirrhosis and diabetes mellitus(DM)are both common conditions with significant socioeconomic burden and impact on morbidity and mortality.A bidirectional relationship exists between DM and liver cirrhosis regard...Liver cirrhosis and diabetes mellitus(DM)are both common conditions with significant socioeconomic burden and impact on morbidity and mortality.A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications.Type 2 DM(T2DM)is a wellrecognized risk factor for chronic liver disease and vice-versa,DM may develop as a complication of cirrhosis,irrespective of its etiology.Liver transplantation(LT)represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease(NAFLD),which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM.The metabolic risk factors including immunosuppressive drugs,can contribute to persistent or de novo development of DM and NAFLD after LT.T2DM,obesity,cardiovascular morbidities and renal impairment,frequently associated with metabolic syndrome and NAFLD,may have negative impact on short and long-term outcomes following LT.The treatment of DM in the context of chronic liver disease and post-transplant is challenging,but new emerging therapies such as glucagon-like peptide-1 receptor agonists(GLP-1RAs)and sodium–glucose cotransporter 2 inhibitors(SGLT2i)targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.展开更多
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.
基金National Natural Science Foundation of China,No.82060161,81960154,and 81760156Jiangxi Provincial Youth Science Foundation,No.2018ACB21040+1 种基金Natural Science Foundation of Jiangxi Province,No.20212BAB206020and Foundation of Health commission of Jiangxi Province,No.SKJP220225830.
文摘BACKGROUND The small intestine is known to play a crucial role in the development and remission of diabetes mellitus(DM).However,the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood.AIM To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism.METHODS Streptozotocin(STZ)was used to induce DM in Sprague-Dawley(SD)rats at a dose of 60 mg/kg.The rats were then randomly divided into two groups:The mid-small intestine bypass(MSIB)group and the sham group(underwent switch laparotomy).Following a 6-wk recovery period post-surgery,the rats underwent various assessments,including metabolic parameter testing,analysis of liver glycogen levels,measurement of key gluconeogenic enzyme activity,characterization of the gut microbiota composition,evaluation of hormone levels,determination of bile acid concentrations,and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor.RESULTS The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism,along with increased hepatic glycogen content.Furthermore,there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase.Importantly,the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus,Clostridium symbiosum,Ruminococcus gnavus,and Bilophila.Moreover,higher levels of secondary bile acids,such as intestinal lithocholic acid,were observed in this group.Remarkably,the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1(GLP-1)at 6 wk postoperatively,highlighting their potential role in glucose regulation.These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota.CONCLUSION The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats.This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1,resulting in a favorable modulation of glucose homeostasis.
文摘In this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GLP-1RA)therapy in the management of type 2 diabetes(T2D)associated with obesity.Bariatric surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D,but information on newer GLP-1RAs in these groups is predictably limited.In older individuals(age>65 years),both bariatric surgery and GLP-1RA therapy improve cardiovascular outcomes.Baria-tric surgery is not infrequently associated with post-operative postprandial hypoglycemia,which is not the case with GLP-1RAs and,paradoxically,there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial hypoglycemia.Comparative trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.
文摘Liver cirrhosis and diabetes mellitus(DM)are both common conditions with significant socioeconomic burden and impact on morbidity and mortality.A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications.Type 2 DM(T2DM)is a wellrecognized risk factor for chronic liver disease and vice-versa,DM may develop as a complication of cirrhosis,irrespective of its etiology.Liver transplantation(LT)represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease(NAFLD),which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM.The metabolic risk factors including immunosuppressive drugs,can contribute to persistent or de novo development of DM and NAFLD after LT.T2DM,obesity,cardiovascular morbidities and renal impairment,frequently associated with metabolic syndrome and NAFLD,may have negative impact on short and long-term outcomes following LT.The treatment of DM in the context of chronic liver disease and post-transplant is challenging,but new emerging therapies such as glucagon-like peptide-1 receptor agonists(GLP-1RAs)and sodium–glucose cotransporter 2 inhibitors(SGLT2i)targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
