YAP regulates the liver size during the fasting-refeeding transition in mice  

作　　者：Xuan Li Shicheng Fan Chenghui Cai Yue Gao Xinhui Wang Yifei Zhang Hangfei Liang Huilin Li Jie Yang Min Huang Huichang Bi 

机构地区：[1]Guangdong Provincial Key Laboratory of New Drug Design and Evaluation,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China [2]NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China [3]School of Pharmaceutical Sciences(Shenzhen),Sun Yat-sen University,Shenzhen 518000,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第4期1588-1599,共12页药学学报（英文版）

基　　金：supported by the National Key R&D Program of China(2022YFA1104900);the Natural Science Foundation of China(Grant number:82025034,81973392);the Shenzhen Science and Technology Program(KQTD20190929174023858,China);the 111 project(Grant number:B16047,China);the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(Grant number:2017BT01Y093,China);the National Engineering and Technology Research Center for New drug Druggability Evaluation(Seed Program of Guangdong Province,Grant number:2017B090903004,China)。

摘　　要：Liver is the central hub regulating energy metabolism during feeding-fasting transition.Evidence suggests that fasting and refeeding induce dynamic changes in liver size,but the underlying mechanisms remain unclear.Yes-associated protein(YAP)is a key regulator of organ size.This study aims to explore the role of YAP in fasting-and refeeding-induced changes in liver size.Here,fasting significantly reduced liver size,which was recovered to the normal level after refeeding.Moreover,hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting.Conversely,refeeding promoted hepatocyte enlargement and proliferation compared to fasted state.Mechanistically,fasting or refeeding regulated the expression of YAP and its downstream targets,as well as the proliferation-related protein cyclin D1(CCND1).Furthermore,fasting significantly reduced the liver size in AAV-control mice,which was mitigated in AAV Yap(5SA)mice.Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation.Besides,the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice.Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation.In summary,this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition,which provides new evidence for YAP in regulating liver size under energy stress.

关 键 词：LIVER FASTING REFEEDING Yes-associated protein Hepatocyte size Hepatocyte proliferation β-Catenin Cyclin D1 

分 类 号：R965[医药卫生—药理学]