The P72R Polymorphism of p53 Predisposes to Obesity and Metabolic Dysfunction
作者: Che-Pei KungJulia I-Ju LeuSubhasree BasuSakina KhakuFrederick Anokye-DansoQin LiuDonna L. GeorgeRexford S. AhimaMaureen E. Murphy
作者单位: 1Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA
2Department of Genetics, The Perelman School at the University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
3Institute for Diabetes, Obesity, and Metabolism, The Perelman School at the University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
4Biostatistics Unit, The Wistar Institute, Philadelphia, PA 19104, USA
刊名: Cell Reports, 2016, Vol.14 (10), pp.2413-2425
来源数据库: Elsevier Journal
DOI: 10.1016/j.celrep.2016.02.037
关键词: p53obesitydiabetesislet hypertrophyNAFLDlipid metabolisminflammationPck1Ccl2TnfNpc1l1
原始语种摘要: Summary(#br)p53 is well known for its tumor suppressor role, but this protein also has a poorly understood role in the regulation of metabolism. Human studies have implicated a common polymorphism at codon 72 of p53 in diabetic and pre-diabetic phenotypes. To understand this role, we utilized a humanized mouse model of the p53 codon 72 variants and monitored these mice following challenge with a high-fat diet (HFD). Mice with the arginine 72 (R72) variant of p53 developed more-severe obesity and glucose intolerance on a HFD, compared to mice with the proline 72 variant (P72). R72 mice developed insulin resistance, islet hypertrophy, increased infiltration of immune cells, and fatty liver disease. Gene expression analyses and studies with small-molecule inhibitors indicate that the p53...
全文获取路径: Elsevier  (合作)
分享到:
来源刊物:

×
关键词翻译
关键词翻译
  • intolerance 不耐性
  • diabetic 糖尿病患者
  • islet 
  • insulin 胰岛素
  • codon 码字
  • inflammation 炎症
  • variant 变体
  • metabolism 代谢
  • developed 开发
  • humanized 人化的