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.
Department of Internal Medicine, Ribeirao Preto Medical School of University of Sao Paulo, Sao Paulo, Brazil.
Nutrition. 2018 Oct;54:94-99. doi: 10.1016/j.nut.2018.02.016. Epub 2018 Mar 21.
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.
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.
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.
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.
减重手术后，代谢调节剂哺乳动物雷帕霉素靶蛋白（mTOR）信号通路网络的改变可能导致与能量来源可用性、全身营养物质以及分解代谢和合成代谢细胞过程相关的分子改变。本研究旨在确定肥胖患者在接受减重手术后 mTOR 复合物 2 亚基信号通路相关的基因表达变化。
实验组包括 13 名接受 Roux-en-Y 胃旁路术（RYGB）术前（术前）和术后 6 个月（术后）检查的肥胖女性。对照组包括 9 名年龄匹配且无其他代谢疾病（即无糖尿病、无肝或肾病）的明显肥胖女性。采集外周血单核细胞样本进行 RNA 提取和随后的微阵列分析。
经过这种方法程序，我们鉴定出 47000 个差异表达基因。随后的生物信息学分析表明，三个差异表达基因（雷帕霉素不敏感伴侣 mTOR [RICTOR]、磷酸肌醇-3-激酶调节亚基 1 [PIK3R1]和缺氧诱导因子 1 亚基 1A [HIF1A]）参与了 mTOR 信号通路。实时定量聚合酶链反应显示，RYGB 手术后 6 个月 RICTOR、PIK3R1 和 HIF1A 上调（P<0.05）。此外，实验组患者体重显著减轻，生化/代谢指标显著改善。
RYGB 手术引起的体重减轻改变了 mTOR 信号通路，特别是 mTOR 复合物 2 亚基。该通路中基因的表达增加，如 RICTOR、PIK3R1 和 HIF1A，反映了诱导的体重减轻和改善的代谢指标（如胰岛素抵抗和脂肪分解），这在本研究中得到了证实。
