PMID- 26709097 OWN - NLM STAT- MEDLINE DCOM- 20160915 LR - 20220409 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 24 IP - 2 DP - 2016 Feb TI - Tumor suppressor RIZ1 in obesity and the PI3K/AKT/mTOR pathway. PG - 389-97 LID - 10.1002/oby.21364 [doi] AB - 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. CI - (c) 2015 The Obesity Society. FAU - Xie, Xiaolei AU - Xie X AD - State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China. FAU - Man, Xian AU - Man X AD - State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China. FAU - Zhu, Zuobin AU - Zhu Z AD - State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China. FAU - Yuan, Dejian AU - Yuan D AD - State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China. FAU - Huang, Shi AU - Huang S AD - State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151226 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (DNA-Binding Proteins) RN - 0 (Multiprotein Complexes) RN - 0 (Nuclear Proteins) RN - 0 (Transcription Factors) RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) RN - EC 2.1.1.43 (PRDM2 protein, human) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - DNA-Binding Proteins/*genetics MH - Gene Expression Profiling MH - Histone-Lysine N-Methyltransferase/*genetics MH - Insulin Resistance/*genetics MH - Male MH - Mechanistic Target of Rapamycin Complex 1 MH - Mice MH - Multiprotein Complexes/genetics MH - Nuclear Proteins/*genetics MH - Obesity/*genetics/metabolism MH - Random Allocation MH - TOR Serine-Threonine Kinases/genetics MH - Transcription Factors/*genetics EDAT- 2015/12/29 06:00 MHDA- 2016/09/16 06:00 CRDT- 2015/12/29 06:00 PHST- 2015/07/23 00:00 [received] PHST- 2015/09/17 00:00 [revised] PHST- 2015/09/22 00:00 [accepted] PHST- 2015/12/29 06:00 [entrez] PHST- 2015/12/29 06:00 [pubmed] PHST- 2016/09/16 06:00 [medline] AID - 10.1002/oby.21364 [doi] PST - ppublish SO - Obesity (Silver Spring). 2016 Feb;24(2):389-97. doi: 10.1002/oby.21364. Epub 2015 Dec 26.