Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Cell Mol Gastroenterol Hepatol. 2019;7(2):275-284. doi: 10.1016/j.jcmgh.2018.09.017. Epub 2018 Oct 10.
A hepatic comorbidity of metabolic syndrome, known as nonalcoholic fatty liver disease (NAFLD), is increasing in prevalence in conjunction with the pandemics of obesity and diabetes. The spectrum of NAFLD ranges from simple hepatic fat accumulation to a more severe disease termed nonalcoholic steatohepatitis (NASH), involving inflammation, hepatocyte death, and fibrosis. Importantly, NASH is linked to a much higher risk of cirrhosis, liver failure, and hepatocellular carcinoma, as well as an increased risk for nonhepatic malignancies and cardiovascular disease. Interest in the understanding of the disease processes and search for treatments for the spectrum of NAFLD-NASH has increased exponentially, but there are no approved pharmacologic therapies. In this review, we discuss the existing literature supporting insulin-sensitizing thiazolidinedione compounds as potential drug candidates for the treatment of NASH. In addition, we put these results into new context by summarizing recent studies suggesting these compounds alter mitochondrial metabolism by binding and inhibiting the mitochondrial pyruvate carrier.
代谢综合征的肝脏合并症，即非酒精性脂肪性肝病（NAFLD），随着肥胖症和糖尿病的流行，其发病率正在上升。NAFLD 的范围从单纯的肝脂肪堆积到更严重的疾病，即非酒精性脂肪性肝炎（NASH），涉及炎症、肝细胞死亡和纤维化。重要的是，NASH 与肝硬化、肝功能衰竭和肝细胞癌的风险大大增加有关，以及非肝脏恶性肿瘤和心血管疾病的风险增加。人们对了解疾病过程和寻找治疗 NAFLD-NASH 谱的方法的兴趣呈指数级增长，但目前还没有批准的药物治疗方法。在这篇综述中，我们讨论了支持胰岛素增敏噻唑烷二酮化合物作为 NASH 治疗潜在药物候选物的现有文献。此外，我们通过总结最近的研究结果，将这些结果置于新的背景下，这些研究表明这些化合物通过结合和抑制线粒体丙酮酸载体来改变线粒体代谢。
