Mammalian target of rapamycin complex 2 signaling in obese women changes after bariatric surgery

Author(s)

de Souza Pinhel, Marcela Augusta ^{[1, 2]} ; Nicoletti, Carolina Ferreira ^[1] ; Noronha, Natalia Yumi ^[1] ; Parenti de Oliveira, Bruno Affonso ^[1] ; Cortes-Oliveira, Cristiana ^[1] ; Salgado Junior, Wilson ^[3] ; da Silva Junior, Wilson Araujo ^[4] ; Silva Souza, Doroteia Rossi ^[2] ; Marchini, Julio Sergio ^[1] ; Nonino, Carla Barbosa ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Sao Paulo - Brazil

^[2] Sao Jose Rio Preto Med Sch, Dept Biochem & Mol Biol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Sao Paulo - Brazil

• Document type: Journal article
• Source: NUTRITION; v. 54, p. 94-99, OCT 2018.
• Web of Science Citations: 1

Abstract

Objectives: After bariatric surgery, modifications to signaling pathway networks including those of the metabolic regulator called mammalian or mechanistic target of rapamycin (mTOR) may lead to molecular alterations related to energy source availability, systemic nutrients, and catabolic and anabolic cellular processes. This study aimed to identify gene expression changes with regard to the mTOR complex 2 subunit signaling pathway in obese patients before and after bariatric surgery. Methods: The experimental group included 13 obese women who were examined before (preoperative) and 6 mo after (postoperative) Roux-en-Y gastric bypass (RYGB) surgery. The control group included nine apparently eutrophic women matched by age and without any other metabolic diseases (i.e., no diabetes and no liver or kidney diseases). Peripheral blood mononuclear cell samples were collected for RNA extraction and subsequent microarray analysis. Results: After this methodological procedure, we identified 47 000 differentially expressed genes. A subsequent bioinformatic analysis showed that three diferentially expressed genes (rapamycin-insensitive companion of mTOR {[}RICTOR], phosphoinositide-3-kinase regulatory subunit 1 {[}PIK3 RI], and hypoxia inducible factor 1 alpha subunit 1A {[}HIF1 A]) participated in the mTOR signaling pathway. Real-time quantitative polymerase chain reaction revealed that RICTOR, PIK3 R1, and HIFI A were upregulated 6 mo after RYGB surgery (P < 0.05). In addition, patients in the experimental group lost weight significantly and presented significant improvement in biochemical/metabolic variables. Conclusions: The weight loss that was induced by RYGB surgery alters the mTOR signaling pathway and specifically the mTOR complex 2 subunit. The increased expression of genes that act in this pathway such as RICTOR, PIK3 R1, and HIFI A reflects the induced weight loss and improved metabolic indicators (e.g., insulin resistance and lipolysis) that are evidenced in this study. (C) 2018 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 13/12819-4 - Genetic, clinical, biochemical and heart rate variability changes in grade III Obesity pre and post bariatric surgery
• Grantee: Marcela Augusta de Souza Pinhel
• Support Opportunities: Scholarships in Brazil - Post-Doctoral