Page 29 - 南京医科大学学报自然科学版

第41卷第12期 南京医科大学学报（自然科学版）
2021年12月 Journal of Nanjing Medical University（Natural Sciences） ·1735 ·

·基础医学·

去泛素化酶YOD1调控肝脏脂代谢的初步研究

周子欣，杨旭乐，张 许，李 仲 *
南京医科大学罕见代谢性疾病研究重点实验室，南京医科大学生物化学与分子生物学系，江苏省人类功能基因组重点实验室，
江苏 南京 211166

［摘 要］ 目的：探索去泛素化酶YOD1在肝脏营养代谢中发挥的作用。方法：通过Q⁃PCR检测高脂饮食C57BL/6小鼠、db/db
小鼠肝脏中以及油酸（oleic acid，OA）处理后的 Hepa1⁃6 细胞内，YOD1 的表达情况。在 C57BL/6 小鼠中，通过 Q⁃PCR 法检测
YOD1的组织分布及不同营养状态下的表达情况。对Hepa1⁃6细胞中给予OA处理，通过甘油三酯试剂盒检测细胞内甘油三脂
含量，并利用油红染色观察细胞内脂滴。经Q⁃PCR和蛋白免疫印迹法检测细胞内相关基因的mRNA及蛋白水平。结果：短期
高脂饮食后，肝脏中 YOD1 的 mRNA 水平显著下降。而与对照组 db/+小鼠相比，db/db 小鼠肝脏中 YOD1 的 mRNA 水平无变
化。但是，经OA处理后，Hepa1⁃6细胞内的YOD1的mRNA水平明显减少。另外，YOD1主要表达于肝脏中。小鼠禁食后，肝脏
YOD1的mRNA水平显著增加，而再喂食后显著下降。此外，过表达YOD1的Hepa1⁃6细胞中OA诱导的脂质堆积明显减少，且
SREBP⁃1c的剪切被抑制。结论：本研究初步发现，去泛素化酶YOD1的表达水平受营养状态调控，并通过抑制SREBP⁃1c的剪
切影响肝细胞的脂代谢。
［关键词］ 非酒精性脂肪肝；YOD1；脂代谢；SREBP⁃1c剪切
［中图分类号］ R329.26 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）12⁃1735⁃06
doi：10.7655/NYDXBNS20211204

Study on YOD1 in regulating liver lipid metabolism

ZHOU Zixin，YANG Xule，ZHANG Xu，LI Zhong *
Key Laboratory of Rare Metabolic Disease，Department of Molecular Biology and Biochemistry，Nanjing Medical
University，the Key Laboratory of Human Functional Genomics of Jiangsu Province，Nanjing 211166，China

［Abstract］ Objective：This study aims to explore the role of deubiquitinating enzyme YOD1 in liver nutrient metabolism. Methods：
The expression of YOD1 in the liver of HFD⁃fed C57BL/6 mice，db/db mice and in Hepa1⁃6 cells after oleic acid（OA）treatment was
checked by Q⁃PCR. Then its tissue distribution in C57BL/6 mice and its expression under different nutritional conditions was detected
by Q⁃PCR. The content of triglycerides in Hepa1⁃6 cells treated with OA was determined by TAG enzymetic kit，and lipid droplets were
observed by Oil Red O staining. Moreover，the mRNA and protein levels of related genes in cells were detected by Q⁃PCR and Western
blot. Results：After a short⁃term HFD⁃fed，the mRNA level of YOD1 in the liver decreased significantly. But compared with that of
db/+ mice in control group，the expression of YOD1 was no change in db/db mice.However，its expression reduced obviously in OA⁃
treated Hepa1⁃6 cells. Besides，YOD1 was mainly distributed in the liver，and we observed that fasting led to increased mRNA level of
YOD1 in mice liver while YOD1 decreased notably after refeeding. Further，YOD1 overexpression remarkably ameliorated OA⁃induced
steatosis in Hepa1⁃6 cells by inhibiting SREBP⁃1c cleavage. Conclusion：YOD1 expression is regulated by nutritional status and
modulates lipid metabolism in hepatocytes by inhibiting SREBP⁃1c cleavage.
［Key words］ non⁃alcoholic fatty liver disease；YOD1；lipid metabolism；SREBP⁃1c cleavage
［J Nanjing Med Univ，2021，41（12）：1735⁃1740］

［基金项目］ 国家自然科学基金（31771307）；南京医科大学 非酒精性脂肪肝（non⁃alcoholic fatty liver dis⁃
科技发展基金（2016NJMU004） ease，NAFLD）是在全球范围内引起慢性肝病的主要
∗ 原因，其典型特征为：在没有大量摄入酒精、感染病
通信作者（Corresponding author），E⁃mail：lizhong@njmu.edu.cn