肾上腺酸作为非酒精性脂肪性肝病中的炎症增强剂。

Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.

作者信息

Horas H Nababan Saut, Nishiumi Shin, Kawano Yuki, Kobayashi Takashi, Yoshida Masaru, Azuma Takeshi

机构信息

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.

出版信息

Arch Biochem Biophys. 2017 Jun 1;623-624:64-75. doi: 10.1016/j.abb.2017.04.009. Epub 2017 Apr 26.

DOI:10.1016/j.abb.2017.04.009

PMID:28456640

Abstract

BACKGROUND

This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD).

METHODS

We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS.

RESULTS

The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend <0.001).

CONCLUSION

Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD.

摘要

背景

本研究旨在确定非酒精性脂肪性肝病（NAFLD）中脂质种类与疾病进展之间的新联系。

方法

我们使用液相色谱/质谱（LC/MS）分析了喂食胆碱缺乏的l-氨基酸定义的高脂饮食（CDAHFD）的db/db小鼠肝脏和血浆中的脂质种类。使用重组人TNFα或IL1β刺激的HepG2细胞进行体外实验。分析了脂肪变性、炎症和纤维化相关基因的表达。还通过LC/MS分析了NAFLD患者的血浆样本。

结果

喂食CDAHFD的患有肝脂肪变性、炎症、轻度纤维化、肥胖和高胆固醇血症的db/db小鼠肝脏和血浆中的游离肾上腺酸水平显著更高（p < 0.05）。喂食CDAHFD的db/db小鼠中积累的肾上腺酸与ELOVL2和5的表达增加以及过氧化物酶体β-氧化过程中酰基辅酶A氧化酶1基因的抑制有关。用肾上腺酸预处理HepG2细胞可增强其细胞因子诱导的细胞因子和趋化因子mRNA表达。在NAFLD患者中，ALT水平最高的组比其他ALT组的血浆肾上腺酸浓度更高（趋势p值<0.001）。