Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease.
Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease.
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DOI：
10.1371/journal.pone.0205747
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Allard JP
中科院分区：
文献类型：
--
作者：
Pettinelli P;Arendt BM;Teterina A;McGilvray I;Comelli EM;Fung SK;Fischer SE;Allard JP
非酒精性脂肪性肝病(NAFLD)，尤其是非酒精性脂肪性肝炎(NASH)是一种常伴有肝纤维化的慢性肝病。NASH患者患肝细胞癌的风险增加。视黄醇代谢异常是参与肝纤维化过程的途径之一，参与视黄醇代谢的酶与肝细胞癌的发生密切相关。我们的目的是确定血浆视黄醇水平与视黄醇代谢相关基因的肝脏表达之间的关系，以及评估视黄酸调节的转录因子在NAFLD患者肝脏中的表达。对17例单纯性脂肪变性(SS)、15例非酒精性脂肪肝(NASH)患者和22例活体肝供者(LD)的肝脏基因表达(Illumina微阵列)和血浆视黄醇水平(HPLC)进行了横断面研究。SS组和NASH组血浆视黄醇水平分别为(1.5 3±0.44)μm ol/L和(1.5 1±0.5 6)μm ol/L，高于LD组(1.2 1±0.38)μm ol/L(p<；0.0 5)。AKR1B10在NASH中的表达高于SS(+6.2倍)和LD(+9.9倍；p=4.89E-11)。视黄醛脱氢酶1家族A2(ALDH1A2)和视黄醛脱氢酶1家族A3(ALDH1A3)是视黄酸合成的关键酶，在SS和NASH中低表达，分别是LD的-1.48倍和-1.47倍，是LD的-2.6倍。在NASH中，肝脏ALDH1A2和ALDH1A3低表达，并与血浆视黄醇水平呈负相关，这可能是肝脏中维甲酸减少的原因。这除了涉及视黄醇代谢的其他基因的表达变化外，还表明了视黄醇稳态改变在NASH中的作用。
Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) is a chronic liver disease commonly associated with hepatic fibrosis. NASH patients have an increased risk for hepatocellular carcinoma (HCC). An altered retinol metabolism is one of the pathways involved in the process of hepatic fibrosis, and enzymes involved in retinol metabolism have been associated with HCC. We aimed to determine the association between plasma retinol levels and hepatic expression of genes related to retinol metabolism, as well as to assess the hepatic expression of transcription factors regulated by retinoic acid in patients with NAFLD. Cross-sectional study where hepatic gene expression (Illumina microarray) and plasma retinol levels (HPLC) were measured in 17 patients with simple steatosis (SS), 15 with NASH, and 22 living liver donors (LD) as controls. Plasma retinol levels were higher in SS (1.53 ± 0.44 μmol/L) and NASH (1.51 ± 0.56 μmol/L) compared to LD (1.21 ± 0.38 μmol/L; p<0.05). AKR1B10 was highly overexpressed in NASH compared to SS (+6.2-fold) and LD (+9.9-fold; p = 4.89E-11). Retinaldehyde dehydrogenase 1 family, member A2 (ALDH1A2) and retinaldehyde dehydrogenase 1 family, member A3 (ALDH1A3), key enzymes for retinoic acid synthesis, were underexpressed in SS (-1.48 and -2.3-fold, respectively) and NASH (-1.47 and -2.6-fold, respectively) versus LD. In NASH, hepatic ALDH1A2 and ALDH1A3 were underexpressed and inversely correlated with plasma retinol levels, which may reduce retinoic acid in the liver. This, in addition to changes in expression of other genes involved in retinol metabolism, suggests a role for altered retinol homeostasis in NASH.
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DOI：
10.3181/0803-rm-94
发表时间：
2008-10
期刊：
Experimental biology and medicine (Maywood, N.J.)
影响因子：
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