title: Tumor suppressor RIZ1 in obesity and the PI3K/AKT/mTOR pathway.
abstract: OBJECTIVE
  The aim of this study was to investigate the shared molecular pathways of obesity and cancer by exploring the role of RIZ1 in obesity and the phospatidylinositol 3-kinase (PI3K)/V-Akt murine thymoma viral oncogene homolog (PKB) (AKT)/mechanistic target of rapamycin (mTOR) pathway.
  
  
  METHODS
  Male wild type (WT) and Riz1(-/-) mice (KO) were fed a standard diet (STD) or a high-fat (HF) diet for up to 8 months. These mice were studied for phenotypic and molecular changes.
  
  
  RESULTS
  Riz1(-/-) mice gained more weight on a HF diet compared to WT mice, with higher free fatty acid and increased visceral fat. Metabolic cage analysis of Riz1(-/-) mice showed lower oxygen consumption but no changes in food intake and ambulatory activity. Riz1(-/-) mice showed impaired glucose regulation but no change in insulin sensitivity. RNA-seq and quantitative RT-PCR analysis found altered expression in certain glycolysis and ATP production genes such as Ubiad1, Atp5g2, and Cyp4a12. The PI3K/AKT/mTOR pathway was activated in the Riz1(-/-) mice fed a HF diet with higher Akt3 mRNA levels and increased phosphorylation of AKT (Ser473), mTOR, and S6.
  
  
  CONCLUSIONS
  The results identify RIZ1 as an important regulator of both Akt3 transcription and AKT phosphorylation and suggest a role for RIZ1 in HF-induced obesity and the AKT pathway.
authors.affiliation: State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Xie
authors.affiliation: State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Man
authors.affiliation: State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Zuobin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Dejian
authors.initials: D
authors.lastname: Yuan
authors.affiliation: State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D011897:Random Allocation; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases