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Tumor suppressor RIZ1 in obesity and the PI3K/AKT/mTOR pathway

Xiaolei Xie1, Xian Man1, Zuobin Zhu1

  • 1State Key Lab of Medical Genetics, Xiangya Medical School, Central South University, Changsha, China.

Obesity (Silver Spring, Md.)
|December 29, 2015
PubMed
Abstract

Insights

RIZ1 deficiency exacerbates high-fat diet-induced obesity by altering energy metabolism and activating the PI3K/AKT/mTOR pathway. This highlights RIZ1

Area of Science:

  • Molecular biology
  • Metabolic research
  • Obesity and cancer research

Background:

  • Obesity and cancer share common molecular pathways.
  • The phosphatidylinositol 3-kinase (PI3K)/V-Akt murine thymoma viral oncogene homolog (PKB) (AKT)/mechanistic target of rapamycin (mTOR) pathway is implicated in both conditions.
  • The role of RIZ1 in obesity and its connection to the PI3K/AKT/mTOR pathway requires further investigation.

Purpose of the Study:

  • To investigate the role of RIZ1 in high-fat diet-induced obesity.
  • To explore the involvement of the PI3K/AKT/mTOR pathway in RIZ1-mediated metabolic changes.
  • To understand the shared molecular mechanisms between obesity and cancer.

Main Methods:

  • Male wild type (WT) and RIZ1 knockout (KO) mice were fed standard or high-fat diets for 8 months.
  • Phenotypic changes, including weight gain and body composition, were assessed.
  • Molecular analyses included RNA sequencing, quantitative RT-PCR, and Western blotting to examine gene expression and protein phosphorylation within the PI3K/AKT/mTOR pathway.

Main Results:

  • Riz1(-/-) mice exhibited increased weight gain, visceral fat accumulation, and impaired glucose regulation on a high-fat diet.
  • Lower oxygen consumption was observed in Riz1(-/-) mice, indicating altered energy metabolism.
  • Activation of the PI3K/AKT/mTOR pathway, evidenced by increased Akt3 mRNA and AKT/mTOR/S6 phosphorylation, was observed in Riz1(-/-) mice on a high-fat diet.

Conclusions:

  • RIZ1 is identified as a key regulator of Akt3 transcription and AKT phosphorylation.
  • RIZ1 plays a significant role in high-fat diet-induced obesity.
  • The study suggests a link between RIZ1, obesity, and the AKT signaling pathway, potentially relevant to shared cancer mechanisms.

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