Fuchs Michael
Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, P.O. Box 980341, Richmond, VA 23298-0341, USA.
J Lipids. 2012;2012:934396. doi: 10.1155/2012/934396. Epub 2011 Dec 7.
Non-alcoholic fatty liver disease (NAFLD) is currently evolving as the most common liver disease worldwide. It may progress to liver cirrhosis and liver cancer and is poised to represent the most common indication for liver transplantation in the near future. The pathogenesis of NAFLD is multifactorial and not fully understood, but it represents an insulin resistance state characterized by a cluster of cardiovascular risk factors including obesity, dyslipidemia, hyperglycemia, and hypertension. Importantly, NAFLD also has evolved as independent risk factor for cardiovascular disease. Unfortunately thus far no established treatment does exist for NAFLD. The bile acid-activated nuclear farnesoid X receptor (FXR) has been shown to play a role not only in bile acid but also in lipid and glucose homeostasis. Specific targeting of FXR may be an elegant and very effective way to readjust dysregulated nuclear receptor-mediated metabolic pathways. This review discusses the body's complex response to the activation of FXR with its beneficial actions but also potential undesirable side effects.
非酒精性脂肪性肝病（NAFLD）目前正逐渐成为全球最常见的肝脏疾病。它可能会发展为肝硬化和肝癌，并在不久的将来成为肝脏移植最常见的适应症。NAFLD的发病机制是多因素的，尚未完全明确，但它代表了一种胰岛素抵抗状态，其特征是一系列心血管危险因素，包括肥胖、血脂异常、高血糖和高血压。重要的是，NAFLD也已成为心血管疾病的独立危险因素。不幸的是，迄今为止，尚无针对NAFLD的确立疗法。胆汁酸激活的核法尼醇X受体（FXR）不仅在胆汁酸中发挥作用，还在脂质和葡萄糖稳态中发挥作用。特异性靶向FXR可能是一种巧妙且非常有效的方法，用于重新调整失调的核受体介导的代谢途径。本文综述讨论了机体对FXR激活的复杂反应，包括其有益作用以及潜在的不良副作用。
