The AMPK-TBC1D1-Rab2A axis contributes to hepatic steatosis by stabilizing PPARγ
Zi-Yue Chen1Ya-Ting Sun1Zi-Ming Wang2Min Xu3Zi-Yun Guo1Jie Hong1Ping Rong4Qi Wang4Hong-Yu Wang4Hua Wang2,5Shuai Chen4Liang Chen1
1. College of life science,Anhui Medical University2. Department of Oncology,the First Affiliated Hospital of Anhui Medical University3. College of Life Sciences,Wuhan University4. MOE Key Laboratory of Model Animal for Disease Study,Department of Endocrinology,Nanjing Drum Tower Hospital,Model Animal Research Center,School of Medicine,Nanjing University5. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province
摘要：<正>Non-alcoholic fatty liver disease（NAFLD） affects about a quarter of population worldwide and persistent overnutrition is one of the major causes.However,the underlying molecular basis has not been fully elucidated and there has no approved drug therapy.Here,we identified a regulatory mechanism that implicates Rab2 A,a novel Rab protein,in the progression of NAFLD based on the energy status and PPARy.The mechanistic analysis showed that nutrition repletion suppressed the phosphorylation of AMPK-TBC1 D1 signaling,augmented the level of GTP-bound Rab2 A and then increased the protein stability of PPARy,which ultimately promoted the hepatic accumulation of lipids in vitro and in vivo.