Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and...Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and cirrhosis.Although NAFLD is a disease of disordered metabolism,it also involves several immune cell-mediated inflammatory processes,either promoting and/or suppressing hepatocyte inflammation through the secretion of pro-inflammatory and/or anti-inflammatory factors to influence the NAFLD process.However,the underlying disease mechanism and the role of immune cells in NAFLD are still under investigation,leaving many open-ended questions.In this review,we presented the recent concepts about the interplay of immune cells in the onset and pathogenesis of NAFLD.We also highlighted the specific non-immune cells exhibiting immunological properties of therapeutic significance in NAFLD.We hope that this review will help guide the development of future NAFLD therapeutics.展开更多
OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabol...OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabolic syndrome.The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome.So,our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides(APS)extracted from Astragalus mongholicus Bunge in high-fat diet(HFD)fed mice.METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS.Then,targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids(SCFAs)and bacteria that were specifically enriched by APS.Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium.Finally,the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice.RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota.Moreover,our results indicated that SCFAs,predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment.Metagenomics revealed that D.vulgaris from Desulfovibrio genus was not only enriched by APS,but also a potent generator of acetic acid,which showed significant anti-NAFLD effects in HFD fed mice.In addition,D.vulgaris modulated the hepatic gene expression pattern of lipids metabolism,particularly suppressed hepatic fatty acid synthase(FASN)and CD36 protein expression.CONCLUSION APS enriched D.vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid,and modulation on hepatic lipids metabolism in mice.Further studies are warranted to explore the long-term impacts of D.vulgaris on host metabolism and the underlying mechanism.展开更多
OBJECTIVE To investigate the protective effect and potential mechanism of desmethylbellidifolin(DMB)in chronic alcoholic fatty liver disease.METHODS C57BL/6 mice were randomly divided into five groups.Control,metadoxi...OBJECTIVE To investigate the protective effect and potential mechanism of desmethylbellidifolin(DMB)in chronic alcoholic fatty liver disease.METHODS C57BL/6 mice were randomly divided into five groups.Control,metadoxine and DMB group(high dose and low dose)mice were fed with Lieber-DeCarli liquid diet containing 5%alcohol for six weeks.Pair-fed group mice were fed with a liquid diet containing the same calories.After treatment,serum GOT,GPT,TG and hepatic T-CHO,TG,GSH,GSH-Px,SOD and CAT levels were measured.Ectopic liver lipid deposition was determined by oil red O and hematoxylin-eosin(HE)staining.Lipid metabolism and autophagy related genes expression were determined by real-time PCR and Western blotting.Electron microscope and laser scanning confocal microscope were used to detect autophagosome and autophagy flux.RESULTS DMB treatment markedly reduced serum TG,GOT and GPT levels in alcohol-induced mice,as well as hepatic levels of T-CHO,TG and MDA,while increased the GSH,GSH-Px,SOD and CAT levels in the liver.Oil red O and HE staining showed that the alcohol-induced lipid accumulation and hepatocyte morphology changes were significantly improved by DMB treatment.Mechanistically,the expression of stearoyl-CoA desaturase 1 and fatty acid synthase were significantly decreased,while lipolysis related hormone-sensitive lipase was elevated in mouse liver by DMB treatment.In addition,DMB could inhibit the phosphorylation of Akt and mTORC1,and activate autophagy process by inducing autophagy related genes expression,such as LC3,ATG5 and ATG7.Moreover,treatment with DMB notably increased the number of autolysosome and promote the autophagy flux,which may therefore induce the lipolysis and oxidation of lipids and prevent the alcohol-induced excessive lipid accumulation in the liver.CONCLUSION DMB exerts a protective role in alcoholic fatty liver disease by regulating the Akt-mTORC1 pathway mediated autophagy activation.展开更多
Fatty liver in dairy cows, which is associated with decreased metabolic function of the liver, develops during times of elevated non-esterified fatty acid （NEFA） concentrations in the blood when the hepatic uptake o...Fatty liver in dairy cows, which is associated with decreased metabolic function of the liver, develops during times of elevated non-esterified fatty acid （NEFA） concentrations in the blood when the hepatic uptake of lipids exceeds the oxidation and secretion of lipids by the liver and then it will cause hepatic accumulation of triglyceride （TG）. The condition is often related to decreased health status, well-being, productivity, and reproductive performance of cows. Prevention of fatty liver in the transition period is always better than any treatments. The nutritional preventative strategies mainly focus either on decreasing the supply of NEFA to liver, and it aims to improve liver function or optimize the capacity then to dispose of NEFA by exporting them as triglycerides in lipoproteins （VLDL）. Good dry cow nutritional programs, combined with excellent feeding management to achieve high levels of dry matter intake throughout the transition period should be the first priority for management. Several different compounds can promote these metabolic actions. The addition of glucose precursors such as glycerol, propyelene glycol, or propionate salts to the feed in the transition diet can modify metabolism in a manner to decrease fatty acid mobilization from adipose tissue and reduce the likelihood of liver TG accumulation. Supplying some other specific nutrients to dairy cows during the transition period may increase rates of NEFA disposal, with resulting effects on performance, though the hepatic capacities for export as triglycerides within VLDL are relatively limited in ruminants. Further studies examining nutritional and management strategies are required to develop new preventive or treatment options that are more practical to reduce the occurrence of fatty liver and its adverse metabolic effects.展开更多
Nicotinic acid (N.C.)and choline were given orally to the periparturient cows to treat and prevent fatty liver.Blood parameters of glucose,β-hydroxybutyrate,albumin,total protein,magnesium,aspartate aminotransferase(...Nicotinic acid (N.C.)and choline were given orally to the periparturient cows to treat and prevent fatty liver.Blood parameters of glucose,β-hydroxybutyrate,albumin,total protein,magnesium,aspartate aminotransferase(AST)and non-esterified fatty acid (NEFA)weremeasured.There were no significant differences betWeen the treated and untreated groups in theplasma concentrations of albumin,total, protein and magnesium.Significant decrease in plasmaconcentrations of β-hydroxybutyrate,NEFA and AST were observed in the treated cows followiug administration of N.C.and choline.All the fatty liver cows(100% )treated with N.C.andcholine recovered within 5 weeks after calving compared with 71.4%(5/7) of untreated cows recovered.The incident rate of fatty liver postpartum in the cows with N.C.and cholinc given 2 weeksbefore calving was 30%(3/10),and the affected cows had a range of mild to moderate fatty liverwhilst the incident rate was 50% (5/10)in the untreated cows,which had a range of mild to ofsevere fatty liver.Meanwhile,the treated cows had a significant higher prodection of milk and shorter intervals from calving to uterine involution, to the first postpartum ovulation and to conception.展开更多
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and cirrhosis.Although NAFLD is a disease of disordered metabolism,it also involves several immune cell-mediated inflammatory processes,either promoting and/or suppressing hepatocyte inflammation through the secretion of pro-inflammatory and/or anti-inflammatory factors to influence the NAFLD process.However,the underlying disease mechanism and the role of immune cells in NAFLD are still under investigation,leaving many open-ended questions.In this review,we presented the recent concepts about the interplay of immune cells in the onset and pathogenesis of NAFLD.We also highlighted the specific non-immune cells exhibiting immunological properties of therapeutic significance in NAFLD.We hope that this review will help guide the development of future NAFLD therapeutics.
基金National Natural Science Foundation of China(81873059,82004016)。
文摘OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabolic syndrome.The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome.So,our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides(APS)extracted from Astragalus mongholicus Bunge in high-fat diet(HFD)fed mice.METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS.Then,targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids(SCFAs)and bacteria that were specifically enriched by APS.Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium.Finally,the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice.RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota.Moreover,our results indicated that SCFAs,predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment.Metagenomics revealed that D.vulgaris from Desulfovibrio genus was not only enriched by APS,but also a potent generator of acetic acid,which showed significant anti-NAFLD effects in HFD fed mice.In addition,D.vulgaris modulated the hepatic gene expression pattern of lipids metabolism,particularly suppressed hepatic fatty acid synthase(FASN)and CD36 protein expression.CONCLUSION APS enriched D.vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid,and modulation on hepatic lipids metabolism in mice.Further studies are warranted to explore the long-term impacts of D.vulgaris on host metabolism and the underlying mechanism.
文摘OBJECTIVE To investigate the protective effect and potential mechanism of desmethylbellidifolin(DMB)in chronic alcoholic fatty liver disease.METHODS C57BL/6 mice were randomly divided into five groups.Control,metadoxine and DMB group(high dose and low dose)mice were fed with Lieber-DeCarli liquid diet containing 5%alcohol for six weeks.Pair-fed group mice were fed with a liquid diet containing the same calories.After treatment,serum GOT,GPT,TG and hepatic T-CHO,TG,GSH,GSH-Px,SOD and CAT levels were measured.Ectopic liver lipid deposition was determined by oil red O and hematoxylin-eosin(HE)staining.Lipid metabolism and autophagy related genes expression were determined by real-time PCR and Western blotting.Electron microscope and laser scanning confocal microscope were used to detect autophagosome and autophagy flux.RESULTS DMB treatment markedly reduced serum TG,GOT and GPT levels in alcohol-induced mice,as well as hepatic levels of T-CHO,TG and MDA,while increased the GSH,GSH-Px,SOD and CAT levels in the liver.Oil red O and HE staining showed that the alcohol-induced lipid accumulation and hepatocyte morphology changes were significantly improved by DMB treatment.Mechanistically,the expression of stearoyl-CoA desaturase 1 and fatty acid synthase were significantly decreased,while lipolysis related hormone-sensitive lipase was elevated in mouse liver by DMB treatment.In addition,DMB could inhibit the phosphorylation of Akt and mTORC1,and activate autophagy process by inducing autophagy related genes expression,such as LC3,ATG5 and ATG7.Moreover,treatment with DMB notably increased the number of autolysosome and promote the autophagy flux,which may therefore induce the lipolysis and oxidation of lipids and prevent the alcohol-induced excessive lipid accumulation in the liver.CONCLUSION DMB exerts a protective role in alcoholic fatty liver disease by regulating the Akt-mTORC1 pathway mediated autophagy activation.
基金Supported by National Natural Science Funds (30300259)
文摘Fatty liver in dairy cows, which is associated with decreased metabolic function of the liver, develops during times of elevated non-esterified fatty acid （NEFA） concentrations in the blood when the hepatic uptake of lipids exceeds the oxidation and secretion of lipids by the liver and then it will cause hepatic accumulation of triglyceride （TG）. The condition is often related to decreased health status, well-being, productivity, and reproductive performance of cows. Prevention of fatty liver in the transition period is always better than any treatments. The nutritional preventative strategies mainly focus either on decreasing the supply of NEFA to liver, and it aims to improve liver function or optimize the capacity then to dispose of NEFA by exporting them as triglycerides in lipoproteins （VLDL）. Good dry cow nutritional programs, combined with excellent feeding management to achieve high levels of dry matter intake throughout the transition period should be the first priority for management. Several different compounds can promote these metabolic actions. The addition of glucose precursors such as glycerol, propyelene glycol, or propionate salts to the feed in the transition diet can modify metabolism in a manner to decrease fatty acid mobilization from adipose tissue and reduce the likelihood of liver TG accumulation. Supplying some other specific nutrients to dairy cows during the transition period may increase rates of NEFA disposal, with resulting effects on performance, though the hepatic capacities for export as triglycerides within VLDL are relatively limited in ruminants. Further studies examining nutritional and management strategies are required to develop new preventive or treatment options that are more practical to reduce the occurrence of fatty liver and its adverse metabolic effects.
文摘Nicotinic acid (N.C.)and choline were given orally to the periparturient cows to treat and prevent fatty liver.Blood parameters of glucose,β-hydroxybutyrate,albumin,total protein,magnesium,aspartate aminotransferase(AST)and non-esterified fatty acid (NEFA)weremeasured.There were no significant differences betWeen the treated and untreated groups in theplasma concentrations of albumin,total, protein and magnesium.Significant decrease in plasmaconcentrations of β-hydroxybutyrate,NEFA and AST were observed in the treated cows followiug administration of N.C.and choline.All the fatty liver cows(100% )treated with N.C.andcholine recovered within 5 weeks after calving compared with 71.4%(5/7) of untreated cows recovered.The incident rate of fatty liver postpartum in the cows with N.C.and cholinc given 2 weeksbefore calving was 30%(3/10),and the affected cows had a range of mild to moderate fatty liverwhilst the incident rate was 50% (5/10)in the untreated cows,which had a range of mild to ofsevere fatty liver.Meanwhile,the treated cows had a significant higher prodection of milk and shorter intervals from calving to uterine involution, to the first postpartum ovulation and to conception.
