Branched-chain amino acids and l-carnitine attenuate lipotoxic hepatocellular damage in rat cirrhotic liver.
Branched-chain amino acids and l-carnitine attenuate lipotoxic hepatocellular damage in rat cirrhotic liver.
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支链氨基酸和左旋肉碱可减轻大鼠肝硬化肝细胞的脂毒性肝细胞损伤。
DOI：
10.1016/j.biopha.2020.111181
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发表时间：
2021
影响因子：
7.5
通讯作者：
Takei Y
中科院分区：
文献类型：
--
作者：
Tamai Y;Chen Z;Wu Y;Okabe J;Kobayashi Y;Chiba H;Hui SP;Eguchi A;Iwasa M;Ito M;Takei Y
支链氨基酸(BCAA)逆转营养不良和l-肉碱可减少肝硬变患者的高氨血症和肌肉痉挛。支链氨基酸和l-肉碱参与了葡萄糖和脂肪酸的代谢，但它们在肝硬变中的作用机制还不完全清楚。我们的目标是通过一个肝硬变大鼠模型来确定支链氨基酸和l-卡尼汀的分子机制(S)及其联合作用。四氯化碳诱导大鼠肝硬变10周。在给药的最后6周内，肝硬变大鼠每天灌胃给予支链氨基酸、L肉碱或支链氨基酸和l-肉碱的组合。我们发现，支链氨基酸和l-肉碱治疗显著改善了肝细胞功能，与降低肝硬变中甘油三酯水平、脂肪沉积和脂联素表达有关。脂质组学分析揭示了支链氨基酸和l-肉碱对肝脏脂质成分的动态变化。支链氨基酸和l-肉碱增加了磷脂酰胆碱的全球分子种类。BCAA和l-卡尼汀可显著降低肝脏三酰甘油和磷脂酰胆碱的过氧化氢含量。此外，所有处理组的血清和肝脏三磷酸腺苷水平均显著升高，这归因于成熟心磷脂和线粒体成分基因表达的增加。最后，支链氨基酸和l-肉碱显著减少了肝细胞的死亡。总而言之，支链氨基酸和l-肉碱治疗通过减少过氧化脂质和整体维持肝硬变内线粒体的完整性来减轻肝细胞损伤。支链氨基酸和l-肉碱的这些有效性支持了人类慢性肝病的治疗策略。
Branched-chain amino acids (BCAA) reverse malnutrition andl-carnitine leads to the reduction of hyperammonemia and muscle cramps in cirrhotic patients. BCAA andl-carnitine are involved in glucose and fatty acid metabolism, however their mechanistic activity in cirrhotic liver is not fully understood. We aim to define the molecular mechanism(s) and combined effects of BCAA andl-carnitine using a cirrhotic rat model. Rats were administered carbon tetrachloride for 10 weeks to induce cirrhosis. During the last 6 weeks of administration, cirrhotic rats received BCAA,l-carnitine or a combination of BCAA andl-carnitine daily via gavage. We found that BCAA andl-carnitine treatments significantly improved hepatocellular function associated with reduced triglyceride level, lipid deposition and adipophilin expression, in cirrhotic liver. Lipidomic analysis revealed dynamic changes in hepatic lipid composition by BCAA andl-carnitine administrations. BCAA andl-carnitine globally increased molecular species of phosphatidylcholine. Liver triacylglycerol and phosphatidylcholine hydroperoxides were significantly decreased by BCAA andl-carnitine. Furthermore, serum and liver ATP levels were significantly increased in all treatments, which were attributed to the elevation of mature cardiolipins and mitochondrial component gene expressions. Finally, BCAA andl-carnitine dramatically reduced hepatocellular death. In conclusion, BCAA andl-carnitine treatments attenuate hepatocellular damage through the reduction of lipid peroxides and the overall maintenance of mitochondrial integrity within the cirrhotic liver. These effectiveness of BCAA andl-carnitine support the therapeutic strategies in human chronic liver diseases.
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慢性肝病中的肉碱代谢。
影响因子：
6.1
作者：
Stephan Krähenbühl
通讯作者：
Stephan Krähenbühl
人血浆中磷脂酰胆碱过氧化氢水平低于先前报道的水平。
DOI：
--
发表时间：
2004
期刊：
Lipids 39巻・9号
影响因子：
--
作者：
廣田良夫;Junko Adachi
通讯作者：
Junko Adachi
影响因子：
4.6
作者：
Sasaki Y;Dehnad A;Fish S;Sato A;Jiang J;Tian J;Schröder K;Brandes R;Török NJ
通讯作者：
Török NJ
影响因子：
6.5
作者：
Nishina, Atsuyoshi;Kimura, Hirokazu;Furukawa, Shoei
通讯作者：
Furukawa, Shoei
肝硬化患者完整肝细胞理论的直接证据。
影响因子：
29.4
作者：
S. Kawasaki;H. Imamura;Y. Bandai;K. Sanjo;Y. Idezuki
通讯作者：
Y. Idezuki