Background and Aims:Metabolic-associated steatohepatitis(MASH)is an advanced and progressive liver disease that potentially causes cirrhosis and hepatocellular carcinoma.Exercise is a crucial and effective interventio...Background and Aims:Metabolic-associated steatohepatitis(MASH)is an advanced and progressive liver disease that potentially causes cirrhosis and hepatocellular carcinoma.Exercise is a crucial and effective intervention for ameliorating metabolic dysfunction-associated steatotic liver disease.This study aimed to provide a comprehensive understanding of the underlying mechanisms of MASH,which benefit a broad spectrum of MASH patients,including those who have difficulty engaging in physical activity.Methods:We established a mouse model of MASH and selectively knocked down L-type amino acid transporter 1 and alanine-serinecysteine transporter 2.Mice were fed a high-fat high-cholesterol diet and subjected to either short-or long-term exercise regimens.We assessed the phosphorylation and activity of branched-chain alpha-keto acid dehydrogenase(BCKDH)as well as branched-chain amino acid(BCAA)content in skeletal muscle following exercise.Results:Short-term exercise significantly reduced hepatic steatosis and inflammation without causing notable changes in body weight.It also enhanced BCKDH activity in skeletal muscle and decreased hepatic BCAA accumulation.Muscle-specific overexpression of BCKDH further promoted BCAA catabolism and significantly attenuated hepatic steatosis and inflammation in high-fat high-cholesterol-fed mice.In contrast,muscle-specific Ltype amino acid transporter 1 knockdown,which suppresses BCAA uptake,markedly abolished these beneficial effects.Interestingly,BCKDH overexpression in muscle increased glutamine levels in both the blood and liver.Hepatic alanineserine-cysteine transporter 2 knockdown,which inhibited glutamine uptake,lessened the protective effect of exercise on MASH.Further in vitro study revealed that glutamine derived from myocytes improved redox homeostasis and inhibited lipid accumulation in hepatocytes.Conclusions:Shortterm exercise enhances BCAA catabolism in skeletal muscle and promotes glutamine production,which circulates to the liver to improve redox balance and alleviate MASH.展开更多
AIM： To evaluate the effect of oral intake of branchedchain amino acids （BCAA） on brain perfusion in patients with liver cirrhosis. METHODS： Single photon emission computed tomography scans were performed in 43 pa...AIM： To evaluate the effect of oral intake of branchedchain amino acids （BCAA） on brain perfusion in patients with liver cirrhosis. METHODS： Single photon emission computed tomography scans were performed in 43 patients with cirrhosis and in 15 age-matched healthy subjects. Twenty-nine out of forty-three patients were randomly treated with either BCAA granules or placebo, and single photon emission computed tomography was performed before and after the treatment. We measured the regional cerebral blood flow values using a threedimensional stereotaxic region of interest template. RESULTS： Cirrhotic patients had regions of significant hypoperfusion in the bilateral central （right P = 0.039, P〈0.05; left P = 0.006 P〈0.01）, parietal （right P = 0.028, P〈0.05; left P = 0.009, P〈0.01）, angular （right P = 0.039, P〈0.05; left P = 0.008, P〈0.01）, and left pericallosal segments （P = 0.038 P〈0.05） as compared with healthy subjects. A significant increase in cerebral perfusion was observed 70 min after the oral intake of BCAA in the angular （right P = 0.012, P〈0.05; left P = 0.049, P〈0.05）, temporal （right P = 0.012, P〈0.05; left P=0.038, P〈0.05）, pericallosal segments （right P = 0.025, P〈0.05; left P = 0.049, P〈0.05） and left precentral （P = 0.044, P〈0.05）, parietal （P = 0.040, P〈0.05） and thalamus （P = 0.033, P〈0.05）. No significant change in perfusion was observed in the placebo group. CONCLUSION： Administration of BCAA rapidly improves cerebral perfusion.展开更多
基金supported by the Key Program of the Natural Science Basic Research Plan in Shaanxi Province,China(to LJ,No.2021JZ-28)the Shaanxi Provincial Innovation Capacity Enhancement Program(to LJ,No.2023-CX-PT-33)+2 种基金the Beijing Nova Program(to QB,No.20220484197)the Shaanxi Provincial Department of Science and Technology(to YZ,No.2019SF-077,No.2023KJXX-023)the Natural Science Foundation of Guangdong Province(to SH,No.2021A1515011426).
文摘Background and Aims:Metabolic-associated steatohepatitis(MASH)is an advanced and progressive liver disease that potentially causes cirrhosis and hepatocellular carcinoma.Exercise is a crucial and effective intervention for ameliorating metabolic dysfunction-associated steatotic liver disease.This study aimed to provide a comprehensive understanding of the underlying mechanisms of MASH,which benefit a broad spectrum of MASH patients,including those who have difficulty engaging in physical activity.Methods:We established a mouse model of MASH and selectively knocked down L-type amino acid transporter 1 and alanine-serinecysteine transporter 2.Mice were fed a high-fat high-cholesterol diet and subjected to either short-or long-term exercise regimens.We assessed the phosphorylation and activity of branched-chain alpha-keto acid dehydrogenase(BCKDH)as well as branched-chain amino acid(BCAA)content in skeletal muscle following exercise.Results:Short-term exercise significantly reduced hepatic steatosis and inflammation without causing notable changes in body weight.It also enhanced BCKDH activity in skeletal muscle and decreased hepatic BCAA accumulation.Muscle-specific overexpression of BCKDH further promoted BCAA catabolism and significantly attenuated hepatic steatosis and inflammation in high-fat high-cholesterol-fed mice.In contrast,muscle-specific Ltype amino acid transporter 1 knockdown,which suppresses BCAA uptake,markedly abolished these beneficial effects.Interestingly,BCKDH overexpression in muscle increased glutamine levels in both the blood and liver.Hepatic alanineserine-cysteine transporter 2 knockdown,which inhibited glutamine uptake,lessened the protective effect of exercise on MASH.Further in vitro study revealed that glutamine derived from myocytes improved redox homeostasis and inhibited lipid accumulation in hepatocytes.Conclusions:Shortterm exercise enhances BCAA catabolism in skeletal muscle and promotes glutamine production,which circulates to the liver to improve redox balance and alleviate MASH.
文摘AIM： To evaluate the effect of oral intake of branchedchain amino acids （BCAA） on brain perfusion in patients with liver cirrhosis. METHODS： Single photon emission computed tomography scans were performed in 43 patients with cirrhosis and in 15 age-matched healthy subjects. Twenty-nine out of forty-three patients were randomly treated with either BCAA granules or placebo, and single photon emission computed tomography was performed before and after the treatment. We measured the regional cerebral blood flow values using a threedimensional stereotaxic region of interest template. RESULTS： Cirrhotic patients had regions of significant hypoperfusion in the bilateral central （right P = 0.039, P〈0.05; left P = 0.006 P〈0.01）, parietal （right P = 0.028, P〈0.05; left P = 0.009, P〈0.01）, angular （right P = 0.039, P〈0.05; left P = 0.008, P〈0.01）, and left pericallosal segments （P = 0.038 P〈0.05） as compared with healthy subjects. A significant increase in cerebral perfusion was observed 70 min after the oral intake of BCAA in the angular （right P = 0.012, P〈0.05; left P = 0.049, P〈0.05）, temporal （right P = 0.012, P〈0.05; left P=0.038, P〈0.05）, pericallosal segments （right P = 0.025, P〈0.05; left P = 0.049, P〈0.05） and left precentral （P = 0.044, P〈0.05）, parietal （P = 0.040, P〈0.05） and thalamus （P = 0.033, P〈0.05）. No significant change in perfusion was observed in the placebo group. CONCLUSION： Administration of BCAA rapidly improves cerebral perfusion.
