Department of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Tsu, Japan; Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology, Kawaguchi, Japan.
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Tsu, Japan.
Nutrition. 2021 Jun;86:111194. doi: 10.1016/j.nut.2021.111194. Epub 2021 Feb 10.
Branched-chain amino acids (BCAAs) are used as nutritional support and for improving prognosis in liver cirrhosis. Here we investigate the molecular mechanisms of BCAA treatment and liver damage focused on pathways related to lipopolysaccharide-binding protein (LBP).
Serum LBP levels were measured in cirrhotic patients and in cirrhotic rats treated with BCAA to examine the correlation between liver function and survival. In cirrhotic rats, liver damage, Enterococcus faecalis translocation, serum capsular polysaccharide, and intestinal tight junction levels were assessed. Damaged HepG2 cells were cultured with BCAA-supplemented, BCAA-deficient, or control amino acid medium, followed by examination of LBP expression.
Serum LBP levels were significantly increased in deceased patients individuals with liver cirrhosis. The survival rate in patients with lower serum LBP (<3.48 μg/mL) was significantly improved. In BCAA-treated rat liver samples, protein expression of LBP, toll-like receptor 4 (TLR4), and phosphorylated signal transduction and activator of transcription 3 (STAT3) were significantly reduced. Also in BCAA-treated rats, intestinal zonula occludens gene expression was increased, whereas hepatic translocation of E. faecalis and serum capsular polysaccharide levels were reduced. In damaged HepG2 cells, lipopolysaccharide-induced elevation of LBP expression was rapidly and strongly repressed in BCAA-enriched medium.
Serum LBP level is a prognostic biomarker in liver cirrhosis. BCAA treatment reduced translocation of E. faecalis through intestinal tight junction recovery and reduced LBP expression in the liver, which repressed activation of LBP, toll-like receptor 4, and signal transduction and activator of transcription 3. Our findings suggest that BCAA supplementation protects the liver from damage via multiple pathways.
支链氨基酸（BCAA）被用作营养支持和改善肝硬化的预后。在这里，我们研究了以脂多糖结合蛋白（LBP）相关途径为重点的 BCAA 治疗和肝损伤的分子机制。
测量肝硬化患者和用 BCAA 治疗的肝硬化大鼠的血清 LBP 水平，以检查肝功能与生存率之间的相关性。在肝硬化大鼠中，评估肝损伤、粪肠球菌易位、血清荚膜多糖和肠紧密连接水平。用补充 BCAA、缺乏 BCAA 或对照氨基酸的培养基培养受损的 HepG2 细胞，然后检查 LBP 表达。
血清 LBP 水平在死亡的肝硬化患者中显著升高。血清 LBP 水平较低（<3.48μg/ml）的患者的生存率显著提高。在 BCAA 治疗的大鼠肝组织样本中，LBP、Toll 样受体 4（TLR4）和磷酸化信号转导和转录激活因子 3（STAT3）的蛋白表达显著降低。此外，在 BCAA 治疗的大鼠中，肠闭锁基因表达增加，而肝内粪肠球菌易位和血清荚膜多糖水平降低。在受损的 HepG2 细胞中，脂多糖诱导的 LBP 表达在富含 BCAA 的培养基中迅速而强烈地受到抑制。
血清 LBP 水平是肝硬化的预后生物标志物。BCAA 治疗通过恢复肠紧密连接减少粪肠球菌易位，并减少肝脏中的 LBP 表达，从而抑制 LBP、Toll 样受体 4 和信号转导和转录激活因子 3 的激活。我们的研究结果表明，BCAA 补充通过多种途径保护肝脏免受损伤。
