Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients
Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients
复制标题
DOI：
10.1007/s00535-019-01633-2
复制
发表时间：
2020-02-01
影响因子：
6.3
通讯作者：
Koike, Kazuhiko
中科院分区：
文献类型：
--
作者：
Enooku, Kenichiro;Tsutsumi, Takeya;Koike, Kazuhiko
背景非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）的特征是过量的肝脏脂肪积聚。然而，在从NASH进展到肝硬化的过程中，肝脂肪经常丢失。我们的目的是阐明NASH进展过程中肝脏脂肪丢失的潜在机制。方法2011年11月至2016年3月在东京大学医院对146例NAFLD患者和14例未接受任何糖尿病或血脂异常药物治疗的隐源性肝硬化患者进行肝活检。其中70例患者在禁食过夜后进行肝活检，90例患者在口服葡萄糖耐量试验后5 h进行肝活检。研究了编码几种脂肪酸代谢相关因子的基因的表达差异，并根据NAFLD活动评分与肝组织学变化相关。前瞻性患者随访持续至2018年6月。结果与游离脂肪酸摄入相关的脂肪酸转运蛋白5（FATP 5）水平与组织学进展特征（包括气球样变和纤维化）呈显著负相关。免疫组织化学分析证实了这一点。编码脂肪酸代谢相关蛋白的基因的转录水平在NASH伴严重纤维化和隐源性肝硬化之间相当。此外，一项前瞻性队列研究表明，低FATP 5表达是肝脏脂肪丢失的最重要风险因素。结论NAFLD患者肝脏FATP5表达降低与组织学进展有关，可能与NASH进展为肝硬化过程中肝脏脂肪丢失有关。
Background Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are characterized by the accumulation of excess hepatic fat. However, in the progression from NASH to cirrhosis, hepatic fat is often lost. Our aim was to elucidate the mechanism underlying hepatic fat loss during NASH progression. Methods Liver biopsies were performed at The University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD and 14 patients with cryptogenic cirrhosis who were not being treated with any diabetes or dyslipidemia drugs. Among them, 70 patients underwent liver biopsy after an overnight fast, and 90 patients were biopsied 5 h after an oral glucose tolerance test. Expression differences in genes encoding several fatty acid metabolism-related factors were examined and correlated with hepatic histological changes based on NAFLD activity scores. Prospective patient follow-up continued until June 2018. Results The level of fatty acid transport protein 5 (FATP5), which is associated with free fatty acid intake, was significantly and inversely correlated with features of histological progression, including ballooning and fibrosis. This was confirmed by immunohistochemical analysis. Transcript levels of genes encoding fatty acid metabolism-related proteins were comparable between NASH with severe fibrosis and cryptogenic cirrhosis. Furthermore, a prospective cohort study demonstrated that low FATP5 expression was the most significant risk factor for hepatic fat loss. Conclusions Decreased hepatic FATP5 expression in NAFLD is linked to histological progression, and may be associated with hepatic fat loss during NASH progression to cirrhosis.