You Min, Zhou Zhou, Daniels Michael, Jogasuria Alvin
Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH, USA.
Gene Expr. 2018 May 18;18(2):103-113. doi: 10.3727/105221617X15093738210295. Epub 2017 Nov 2.
Alcoholic liver disease (ALD) is the most prevalent form of liver disease, encompassing a spectrum of progressive pathological changes from steatosis to steatohepatitis to fibrosis/cirrhosis and hepatocellular carcinoma. Alcoholic steatosis/steatohepatitis is the initial stage of ALD and a major risk factor for advanced liver injuries. Adiponectin is a hormone secreted from adipocytes. Fibroblast growth factor (FGF) 15 (human homolog, FGF19) is an ileum-derived hormone. Adipocyte-derived adiponectin and gut-derived FGF15/19 regulate each other, share common signaling cascades, and exert similar beneficial functions. Emerging evidence has revealed that dysregulated adiponectin-FGF15/19 axis and impaired hepatic adiponectin-FGF15/19 signaling are associated with alcoholic liver damage in rodents and humans. More importantly, endocrine adiponectin-FGF15/19 signaling confers protection against ethanol-induced liver damage via fine tuning the adipose-intestine-liver crosstalk, leading to limited hepatic inflammatory responses, and ameliorated alcoholic liver injury. This review is focused on the recently discovered endocrine adiponectin-FGF15/19 axis that is emerging as an essential adipose-gut-liver coordinator involved in the development and progression of alcoholic steatohepatitis.
酒精性肝病（ALD）是最常见的肝病形式，涵盖了从脂肪变性到脂肪性肝炎再到纤维化/肝硬化以及肝细胞癌的一系列渐进性病理变化。酒精性脂肪变性/脂肪性肝炎是ALD的初始阶段，也是晚期肝损伤的主要危险因素。脂联素是一种由脂肪细胞分泌的激素。成纤维细胞生长因子（FGF）15（人类同源物FGF19）是一种由回肠产生的激素。脂肪细胞衍生的脂联素和肠道衍生的FGF15/19相互调节，共享共同的信号级联，并发挥相似的有益功能。新出现的证据表明，脂联素-FGF15/19轴失调以及肝脏脂联素-FGF15/19信号受损与啮齿动物和人类的酒精性肝损伤有关。更重要的是，内分泌脂联素-FGF15/19信号通过微调脂肪-肠道-肝脏的相互作用，对乙醇诱导的肝损伤具有保护作用，从而导致肝脏炎症反应受限，并改善酒精性肝损伤。本综述聚焦于最近发现的内分泌脂联素-FGF15/19轴，该轴正成为参与酒精性脂肪性肝炎发生和发展的重要脂肪-肠道-肝脏协调因子。
