Departments of Internal Medicine and Cellular & Molecular Physiology, Yale University, New Haven, Connecticut, USA.
Obesity (Silver Spring). 2019 Sep;27(9):1385-1387. doi: 10.1002/oby.22559. Epub 2019 Jul 25.
Concordant with soaring obesity rates, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world. The obesity epidemic demands interventions to reverse obesity-associated hepatic steatosis, NAFLD, and nonalcoholic steatohepatitis, and several new pharmacologic approaches have been developed within the past several years. Steatosis develops when energy delivery to the liver, modulated by rates of hepatic lipogenesis, exceeds the capacity of the liver to utilize or export this energy. Therefore, pharmacologic approaches to reverse hepatic steatosis have focused largely, though not exclusively, on (1) reducing substrate availability to the liver, (2) reducing hepatic lipid synthesis, and (3) increasing hepatic mitochondrial fat oxidation (Figure 1). This Perspective will discuss these three classes of emerging pharmacologic therapies against hepatic steatosis, with the ultimate intent to ameliorate NAFLD and/or nonalcoholic steatohepatitis, and the advantages and pitfalls afforded by each strategy to treat these epidemics of obesity-associated liver disease.
与肥胖率飙升相一致，非酒精性脂肪性肝病（NAFLD）已成为世界上最常见的慢性肝病。肥胖症的流行需要采取干预措施来逆转与肥胖相关的肝脂肪变性、NAFLD 和非酒精性脂肪性肝炎，在过去几年中已经开发出几种新的药物治疗方法。当肝脏的能量供应（由肝内脂质生成的速度调节）超过肝脏利用或输出这种能量的能力时，就会发生脂肪变性。因此，逆转肝脂肪变性的药物治疗方法主要集中在（1）减少肝脏的底物供应，（2）减少肝内脂质合成，和（3）增加肝线粒体脂肪氧化（图 1）。本观点将讨论针对肝脂肪变性的这三类新兴药物治疗方法，最终目的是改善 NAFLD 和/或非酒精性脂肪性肝炎，以及每种策略在治疗这些与肥胖相关的肝病流行方面的优势和缺陷。
