Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression.
Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression.
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DOI：
10.1097/mog.0b013e32834e7b4b
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发表时间：
2012-03
影响因子：
2.5
通讯作者：
Zeisel SH
中科院分区：
文献类型：
--
作者：
Corbin KD;Zeisel SH
胆碱是一种必需的营养素，肝脏是负责胆碱代谢的中心器官。脂肪肝和肝细胞死亡发生时，人类被剥夺胆碱。在过去的几年里，我们对影响人类胆碱需求的机制以及胆碱对肝功能的影响的理解有了重大进展。这些进展有助于阐明为什么非酒精性脂肪性肝病（NAFLD）的发生和进展，有时肝癌。食用低胆碱饮食的人会发生脂肪肝和肝损伤。胆碱的饮食需求受到雌激素和胆碱和叶酸代谢特定基因中的单核苷酸多态性（SNP）的调节。胆碱对肝脏的影响范围从脂肪变性到肝癌的发展，并且已经确定了这些影响的几种机制。它们包括异常磷脂合成、脂蛋白分泌缺陷、由线粒体功能障碍引起的氧化损伤和内质网（ER）应激。此外，肝脂肪变性表型可以通过代谢组学特征更充分地表征，并受到肠道微生物组的影响。重要的是，肝功能，一碳代谢和能量代谢之间的复杂联系才刚刚开始阐明。胆碱影响肝功能，对这种营养素的饮食需求取决于个体的基因型和雌激素状态。了解这些个体差异对于胃肠病学家寻求了解为什么有些人会发展NAFLD而其他人不会，以及为什么有些患者耐受全肠外营养而其他患者会发展肝功能障碍非常重要。
Choline is an essential nutrient and the liver is a central organ responsible for choline metabolism. Hepatosteatosis and liver cell death occur when humans are deprived of choline. In the last few years there have been significant advances in our understanding of the mechanisms that influence choline requirements in humans and in our understanding of choline’s effects on liver function. These advances are useful in elucidating why non-alcoholic fatty liver disease (NAFLD) occurs and progresses sometimes to hepatocarcinogenesis. Humans eating low choline diets develop fatty liver and liver damage,. This dietary requirement for choline is modulated by estrogen and by single nucleotide polymorphisms (SNPs) in specific genes of choline and folate metabolism. The spectrum of choline’s effects on liver range from steatosis to development of hepatocarcinomas, and several mechanisms for these effects have been identified. They include abnormal phospholipid synthesis, defects in lipoprotein secretion, oxidative damage caused by mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. Furthermore, the hepatic steatosis phenotype and can be characterized more fully via metabolomic signatures and is influenced by the gut microbiome. Importantly, the intricate connection between liver function, one carbon metabolism, and energy metabolism is just beginning to be elucidated. Choline influences liver function, and the dietary requirement for this nutrient varies depending on an individual’s genotype and estrogen status. Understanding these individual differences is important for gastroenterologists seeking to understand why some individuals develop NAFLD and others do not, and why some patients tolerate total parenteral nutrition and others develop liver dysfunction.