UVRAG基因缺失促进饥饿诱导的肝脏脂肪变性  

UVRAG deficiency exacerbates fasting-induced hepatic steatosis

作　　者：胡晓雯[1] 张沙沙 安琳 AMBER Naz 朱洪新 HU Xiaowen;ZHANG Shasha;AN Lin;AMBER Naz;ZHU Hongxin(Bio-X Institutes,Key Laboratory for Genetics of Developmental and Neuropsychiatric Disorders,Ministry of Education,Shanghai Jiao Tong University,Shanghai 200240,China)

机构地区：[1]上海交通大学Bio-X研究院遗传发育与精神神经疾病教育部重点实验室,上海200240

出　　处：《上海大学学报（自然科学版）》2018年第3期467-475,共9页Journal of Shanghai University:Natural Science Edition

基　　金：国家自然科学创新研究群体基金资助项目(81421061);国家重点基础研究发展计划(973计划)资助项目(2013CB531101);上海市自然科学基金资助项目(16ZR1418200)

摘　　要：[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 protein1,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 autophagyrelated 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.

关 键 词：UVRAG 饥饿 自噬 肝脏脂肪变性 

分 类 号：Q95.331[生物学—动物学]