Liu Yan, Chen Hongen, Wang Jingjing, Zhou Wenjing, Sun Ruifang, Xia Min
Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China
Am J Clin Nutr. 2015 Jul;102(1):130-7. doi: 10.3945/ajcn.114.105155. Epub 2015 May 6.
Retinoic acid (RA), an active metabolite of vitamin A (retinol), has been implicated in the regulation of lipid metabolism and hepatic steatosis in animal models. However, the relation between RA and liver histology in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is unknown.
This study aimed at examining the association of RA with NAFLD and NASH in Chinese subjects.
Serum RA concentration was determined by ELISA in 41 control subjects, 45 patients with NAFLD, and 38 patients with NASH. The associations of RA with adiposity, serum glucose, lipid profiles, and markers of liver damage were studied. Moreover, both mRNA and protein levels of retinoic X receptor α (RXRα) in the liver were analyzed in subjects with different degrees of hepatic steatosis.
Serum RA concentrations in patients with NAFLD (1.42 ± 0.47 ng/mL) and NASH (1.14 ± 0.26 ng/mL) were significantly lower than those in control subjects (2.70 ± 0.52 ng/mL) (P < 0.01). Furthermore, serum RA concentrations were significantly different between subjects with normal glucose tolerance and those with type 2 diabetes in control [2.87 ± 0.52 (n = 28) vs. 2.32 ± 0.44 ng/mL (n = 13)], NAFLD [1.61 ± 0.37 (n = 29) vs. 1.28 ± 0.41 ng/mL (n = 16)], and NASH [1.35 ± 0.34 (n = 24) vs. 1.07 ± 0.29 ng/mL (n = 14)] groups. In human liver tissue, RXRα mRNA expression was inversely correlated with the exacerbation of hepatic steatosis. Both serum RA concentrations and RXRα mRNA levels were inversely correlated with intrahepatic triglyceride content (r = -0.700, P < 0.001, and r = -0.611, P = 0.002, respectively). Compared with grade 0 severity, the concentration of RXRα protein was lower in more severe grades in patients with NAFLD.
These results show that circulating RA concentrations were lower in subjects with NAFLD and were associated with hepatic lipid metabolism and insulin resistance. This trial was registered at clinicaltrials.gov as NCT01940263.
视黄酸（RA）是维生素A（视黄醇）的一种活性代谢产物，在动物模型中参与脂质代谢和肝脏脂肪变性的调节。然而，RA与非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）患者肝脏组织学之间的关系尚不清楚。
本研究旨在探讨中国人群中RA与NAFLD和NASH的关联。
采用酶联免疫吸附测定法（ELISA）测定41名对照者、45例NAFLD患者和38例NASH患者的血清RA浓度。研究RA与肥胖、血糖、血脂谱及肝损伤标志物之间的关联。此外，还分析了不同程度肝脂肪变性患者肝脏中视黄酸X受体α（RXRα）的mRNA和蛋白水平。
NAFLD患者（1.42±0.47 ng/mL）和NASH患者（1.14±0.26 ng/mL）的血清RA浓度显著低于对照者（2.70±0.52 ng/mL）（P<0.01）。此外，在对照组[2.87±0.52（n = 28） vs. 2.32±0.44 ng/mL（n = 13）]、NAFLD组[1.61±0.37（n = 小29） vs. 1.28±0.41 ng/mL（n = 16）]和NASH组[1.35±0.34（n = 24） vs. 1.07±0.29 ng/mL（n = 14）]中，葡萄糖耐量正常者与2型糖尿病患者的血清RA浓度也存在显著差异。在人体肝脏组织中，RXRα mRNA表达与肝脂肪变性的加重呈负相关。血清RA浓度和RXRα mRNA水平均与肝内甘油三酯含量呈负相关（r分别为 -0.700，P<0.001和r = -0.611，P = 0.002）。与0级严重程度相比，NAFLD患者中更严重分级的RXRα蛋白浓度较低。
这些结果表明，NAFLD患者的循环RA浓度较低，且与肝脏脂质代谢和胰岛素抵抗有关。本试验已在clinicaltrials.gov注册，注册号为NCT01940263。
