Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, Tokyo 103-0002, Japan.
Int J Mol Sci. 2018 Oct 8;19(10):3064. doi: 10.3390/ijms19103064.
The rising prevalence of non-alcoholic fatty liver disease (NAFLD) parallels the global increase in the number of people diagnosed with obesity and metabolic syndrome. The gut-liver axis (GLA) plays an important role in the pathogenesis of NAFLD/non-alcoholic steatohepatitis (NASH). In this review, we discuss the clinical significance and underlying mechanisms of action of gut-derived secretory factors in NAFLD/NASH, focusing on recent human studies. Several studies have identified potential causal associations between gut-derived secretory factors and NAFLD/NASH, as well as the underlying mechanisms. The effects of gut-derived hormone-associated drugs, such as glucagon-like peptide-1 analog and recombinant variant of fibroblast growth factor 19, and other new treatment strategies for NAFLD/NASH have also been reported. A growing body of evidence highlights the role of GLA in the pathogenesis of NAFLD/NASH. Larger and longitudinal studies as well as translational research are expected to provide additional insights into the role of gut-derived secretory factors in the pathogenesis of NAFLD/NASH, possibly providing novel markers and therapeutic targets in patients with NAFLD/NASH.
非酒精性脂肪性肝病（NAFLD）的患病率不断上升，与肥胖症和代谢综合征患者数量的全球增长相吻合。肠-肝轴（GLA）在 NAFLD/非酒精性脂肪性肝炎（NASH）的发病机制中起着重要作用。在这篇综述中，我们讨论了源自肠道的分泌因子在 NAFLD/NASH 中的临床意义和作用机制，重点关注最近的人类研究。一些研究已经确定了源自肠道的分泌因子与 NAFLD/NASH 之间的潜在因果关系以及潜在的作用机制。肠源激素相关药物（如胰高血糖素样肽-1 类似物和重组成纤维细胞生长因子 19 变体）以及其他治疗 NASH 的新策略的疗效也已被报道。越来越多的证据强调了 GLA 在 NAFLD/NASH 发病机制中的作用。更大规模和纵向的研究以及转化研究有望为源自肠道的分泌因子在 NAFLD/NASH 发病机制中的作用提供更多的见解，可能为 NAFLD/NASH 患者提供新的标志物和治疗靶点。
