Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease
Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease
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DOI：
10.1152/ajpregu.00677.2010
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发表时间：
2011-12-01
影响因子：
2.8
通讯作者：
Maclean, Kenneth N.
中科院分区：
文献类型：
--
作者：
Gentile, Christopher L.;Nivala, Angela M.;Maclean, Kenneth N.
Gentile CL，Nivala AM，Gonzales JC，Pfaffenbach KT，Wang D，WeY，酱H，Orlky DJ，Petersen DR，Pagliassotti MJ，Maclean KN。牛磺酸治疗非酒精性脂肪性肝病潜力的实验证据。Am J Physiol Regul Integr Comp Physiol 301：R1710-R1722,2011.2011年9月28日首次出版；DOI：10.1152/ajpregu.00677.2010。肥胖症的发病率目前处于流行水平，并已导致非酒精性脂肪性肝病作为一种常见的代谢紊乱出现，可能导致肝脏损伤和肝硬变。饮食中过量的蔗糖和长链饱和脂肪酸可能在NAFLD的发生发展中起一定作用。将蔗糖和饱和脂肪酸与肝脏损伤联系在一起的一个因素是内质网(ER)功能障碍。虽然目前还没有被证明有效的治疗NAFLD的方法，但氨基磺酸牛磺酸对各种代谢紊乱有保护作用，包括酒精诱导的肝损伤。本研究旨在评估牛磺酸对饮食诱导的非酒精性脂肪肝的预防性治疗潜力。我们报道，牛磺酸显著减轻棕榈酸酯介导的caspase-3活性、细胞死亡、内质网应激和H4IIE肝细胞和原代肝细胞的氧化应激。在喂食高蔗糖饮食的大鼠中，补充牛磺酸显著降低了肝脏脂肪堆积、肝脏损伤、炎症、血浆甘油三酯和胰岛素水平。高蔗糖饮食导致肝脏中与内质网应激一致的未折叠蛋白反应的多种成分的诱导，这一点可以通过补充牛磺酸来改善。用内质网应激诱导剂衣霉素处理小鼠，可导致肝脏损伤、未折叠蛋白反应诱导和肝脏脂肪堆积，而补充牛磺酸可显著改善这一现象。我们的结果表明，饮食补充牛磺酸提供了巨大的潜力作为一种预防治疗的NAFLD。
Gentile CL, Nivala AM, Gonzales JC, Pfaffenbach KT, Wang D, Wei Y, Jiang H, Orlicky DJ, Petersen DR, Pagliassotti MJ, Maclean KN. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease. Am J Physiol Regul Integr Comp Physiol 301: R1710-R1722, 2011. First published September 28, 2011; doi:10.1152/ajpregu.00677.2010.The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD.