[目的] 紫外线辐射耐受相关(ultraviolet resistance-associated gene, UVRAG)是一个自噬相关基因,具有多种生物学功能.利用UVRAG基因缺失的小鼠证实了该基因缺失可阻断体内自噬流,并鉴于自噬对脂代谢有一定调控作用,研究了UVRAG在饥饿诱导的肝脏脂肪变性中的作用.[方法与结果] 野生型小鼠和UVRAG基因缺失小鼠给予正常饮食或24 h饥饿处理.在正常生理条件下,油红染色显示UVARG基因缺失小鼠和野生型小鼠肝脏无明显脂质积聚;但是在24 h饥饿条件下, 该基因缺失可导致肝脏脂质积聚显著增多, 且UVRAG基因缺失小鼠肝脏甘油三酯、游离脂肪酸质量比显著升高,而总胆固醇质量比无显著性差异. 实时荧光定量聚合酶链式反应(reverse transcription-polymerize chain reaction, RT-PCR)显示,在正常生理条件下的胆固醇调节元件结合蛋白-1(sterol regulatory element-binding protein 1, SREBP-1)基因在UVRAG基因缺失小鼠肝脏表达显著下调,但在饥饿条件下,UVARG基因缺失小鼠和野生型小鼠肝脏SREBP-1表达无显著差异;而在实验组和对照组中其他肝脏脂代谢相关基因CD 36, FAS, CPT-1, PPAR和FGF 21的表达无显著性变化. 此外,UVARG基因缺失对脂代谢调控分子AMPK活性无显著影响. 在饥饿条件下,UVRAG基因缺失可导致血浆甘油三酯和游离脂肪酸浓度上升, 血糖浓度下降.[结论] UVARAG基因缺失促进饥饿诱导的肝脏脂肪变性,这可能与肝脏自噬阻断和肝脏摄取血浆游离脂肪酸增多有关.

[Objective] Ultraviolet resistance-associated gene (UVRAG) is an autophagy-related protein with multiple functions. Previously that autophagic flux is impaired in UVRAG-deficient mice has been shown. Given that autophagy regulates lipid metabolism, the role of UVRAG in fasting-induced hepatic steatosis was sought to determined. [Methods and results] Wild type (WT) and UVARG-deficient mice were subjected to normal conditions or 24 h fasting. In normal conditions, Oil red O staining showed no difference in hepatic lipid accumulation between WT and UVRAG-deficient mice. However, UVRAG deficiency exacerbates fasting-induced hepatic lipid accumulation compared with WT controls. Real time reverse transcription-polymerize chain reaction (RT-PCR) showed that UVRAG deficiency had no effects on the expression of lipid metabolic gene including CD 36, FAS, CPT-1, PPAR and FGF 21 in normal and fasting conditions. Sterol regulatory element-binding protein 1 (SREBP-1), which was lower in the liver from UVRAG-deficient mice, was comparable between fasted UVRAG-deficient mice and WT controls. Moreover, no difference in AMPK activity was observed in the liver from WT and UVRAG-deficient mice in fasting conditions. Plasma triglyceride and free fatty acid concentration were elevated in fed and fasted UVRAG-deficient mice compared with corresponding WT controls. Plasma cholesterol concentration was not different between WT and UVRAG-deficient mice in normal and fasting conditions. UVRAG deficiency exacerbated fasting-induced reduction in plasma glucose concentration. [Conclusions] UVRAG deficiency exacerbates fasting-induced hepatic steatosis, which may be due to impaired autophagic flux and increased uptake of plasma free fatty acid.