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

Marcela Augusta de Souza Pinhel; Carolina Ferreira Nicoletti; Natalia Yumi Noronha; Bruno Affonso Parenti de Oliveira; Cristiana Cortes-Oliveira; Wilson Salgado Junior; Wilson Araujo da Silva Junior; Doroteia Rossi Silva Souza; Julio Sergio Marchini; Carla Barbosa Nonino

doi:10.1016/j.nut.2018.02.016

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

Nutrition. 2018 Oct:54:94-99. doi: 10.1016/j.nut.2018.02.016. Epub 2018 Mar 21.

Affiliations

¹ Department of Internal Medicine, Ribeirao Preto Medical School of University of Sao Paulo, Sao Paulo, Brazil; Department of Biochemistry and Molecular Biology, Sao Jose do Rio Preto Medical School, Sao Paulo, Brazil.
² Department of Internal Medicine, Ribeirao Preto Medical School of University of Sao Paulo, Sao Paulo, Brazil.
³ Department of Surgery and Anatomy, Ribeirao Preto Medical School of University of Sao Paulo, Sao Paulo, Brazil.
⁴ Department of Genetics, Ribeirao Preto Medical School of University of Sao Paulo, Sao Paulo, Brazil.
⁵ Department of Biochemistry and Molecular Biology, Sao Jose do Rio Preto Medical School, Sao Paulo, Brazil.
⁶ Department of Internal Medicine, Ribeirao Preto Medical School of University of Sao Paulo, Sao Paulo, Brazil. Electronic address: carla@fmrp.usp.br.

PMID: 29778908
DOI: 10.1016/j.nut.2018.02.016

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 R1], 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 HIF1 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 HIF1 A reflects the induced weight loss and improved metabolic indicators (e.g., insulin resistance and lipolysis) that are evidenced in this study.

Keywords: Bariatric surgery; Gene expression; MTORC2; Obesity; RYGB.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Female
Gastric Bypass*
Humans
Leukocytes, Mononuclear / metabolism
Longitudinal Studies
Mechanistic Target of Rapamycin Complex 2 / metabolism*
Middle Aged
Obesity / genetics*
Obesity / surgery
Postoperative Period
Preoperative Period
Signal Transduction / genetics*
Treatment Outcome
Weight Loss / genetics*

Substances

Mechanistic Target of Rapamycin Complex 2