Abstract：
METHODS: Branched-chain amino acids, especially leucine, have been reported to play a role in regulating lipid metabolism. This study aims to examine the effects of leucine deprivation on hepatic lipid metabolism.
RESULTS: C57BL/6 mice are fed with a chow diet (control group, n = 8) or a leucine-free diet (-Leu group, n = 8) for 7 days. Histology, lipidomics, targeted metabolomics, and transcriptomics are performed to analyze the liver tissue. Compared to control group, -Leu group exhibits a notably reduced liver weight, accompanied by hepatic injury, and disorders of lipid metabolism. The level of sphingomyelin (SM) is significantly increased in the liver of -Leu group, while the glycerolipids (GL) level is significantly decreased. The expression of sphingomyelin synthase 1 (SGMS1) is upregulated by leucine deprivation in a time-dependent manner, leading to hepatic SM accumulation. Moreover, leucine deprivation results in hepatic GL loss via suppressing fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1) expression.
CONCLUSIONS: The findings demonstrate that leucine deprivation results in abnormal lipid metabolism in the liver, mainly manifested as SM accumulation and GL loss. These results provide insights into the role of leucine in regulating lipid metabolism.
RESULTS: C57BL/6 mice are fed with a chow diet (control group, n = 8) or a leucine-free diet (-Leu group, n = 8) for 7 days. Histology, lipidomics, targeted metabolomics, and transcriptomics are performed to analyze the liver tissue. Compared to control group, -Leu group exhibits a notably reduced liver weight, accompanied by hepatic injury, and disorders of lipid metabolism. The level of sphingomyelin (SM) is significantly increased in the liver of -Leu group, while the glycerolipids (GL) level is significantly decreased. The expression of sphingomyelin synthase 1 (SGMS1) is upregulated by leucine deprivation in a time-dependent manner, leading to hepatic SM accumulation. Moreover, leucine deprivation results in hepatic GL loss via suppressing fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1) expression.
CONCLUSIONS: The findings demonstrate that leucine deprivation results in abnormal lipid metabolism in the liver, mainly manifested as SM accumulation and GL loss. These results provide insights into the role of leucine in regulating lipid metabolism.
摘要：
方法：支链氨基酸，尤其是亮氨酸,已被报道在调节脂质代谢中发挥作用。本研究旨在研究亮氨酸剥夺对肝脏脂质代谢的影响。
结果：C57BL/6小鼠饲喂食物（对照组，n=8）或无亮氨酸饮食（-Leu组，n=8)持续7天。组织学,脂质组学，靶向代谢组学，和转录组学进行分析肝组织。与对照组相比,-Leu组表现出明显减轻的肝脏重量，伴有肝损伤，和脂质代谢紊乱。-Leu组肝脏的鞘磷脂（SM）水平显着增加，而甘油脂（GL）水平显着降低。鞘磷脂合成酶1(SGMS1)的表达被亮氨酸剥夺以时间依赖性方式上调,导致肝脏SM积累。此外，亮氨酸剥夺通过抑制脂肪酸合酶（FASN）和乙酰辅酶A羧化酶1（ACC1）的表达导致肝GL丢失。
结论：研究结果表明，亮氨酸剥夺导致肝脏脂质代谢异常，主要表现为SM积累和GL损失。这些结果提供了对亮氨酸在调节脂质代谢中的作用的见解。
结果：C57BL/6小鼠饲喂食物（对照组，n=8）或无亮氨酸饮食（-Leu组，n=8)持续7天。组织学,脂质组学，靶向代谢组学，和转录组学进行分析肝组织。与对照组相比,-Leu组表现出明显减轻的肝脏重量，伴有肝损伤，和脂质代谢紊乱。-Leu组肝脏的鞘磷脂（SM）水平显着增加，而甘油脂（GL）水平显着降低。鞘磷脂合成酶1(SGMS1)的表达被亮氨酸剥夺以时间依赖性方式上调,导致肝脏SM积累。此外，亮氨酸剥夺通过抑制脂肪酸合酶（FASN）和乙酰辅酶A羧化酶1（ACC1）的表达导致肝GL丢失。
结论：研究结果表明，亮氨酸剥夺导致肝脏脂质代谢异常，主要表现为SM积累和GL损失。这些结果提供了对亮氨酸在调节脂质代谢中的作用的见解。
