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肥胖症手术旁路术后女性的全球转录谱变化。

Changes in Global Transcriptional Profiling of Women Following Obesity Surgery Bypass.

作者信息

Pinhel Marcela Augusta de Souza, Noronha Natalia Yumi, Nicoletti Carolina Ferreira, de Oliveira Bruno Affonso Parente, Cortes-Oliveira Cristiana, Pinhanelli Vitor Caressato, Salgado Junior Wilson, Machry Ana Julia, da Silva Junior Wilson Araújo, Souza Dorotéia Rossi Silva, Marchini Júlio Sérgio, Nonino Carla Barbosa

机构信息

Department of Internal Medicine, Laboratory of Nutrigenomic Studies, Ribeirao Preto Medical School, FMRP, University of Sao Paulo, USP, Av Bandeirantes, 3900, Monte Alegre, Ribeirao Preto, SP, 14049-900, Brazil.

Department of Surgery and Anatomy, Ribeirao Preto Medical School, FMRP, University of Sao Paulo, USP, Ribeirao Preto, SP, Brazil.

出版信息

Obes Surg. 2018 Jan;28(1):176-186. doi: 10.1007/s11695-017-2828-x.

DOI:10.1007/s11695-017-2828-x
PMID:28735374
Abstract

BACKGROUND

Differential gene expression in peripheral blood mononuclear cells (PBMCs) after Roux-en-Y gastric bypass (RYGB) is poorly characterized. Markers of these processes may provide a deeper understanding of the mechanisms that underlie these events. The main goal of this study was to identify changes in PBMC gene expression in women with obesity before and 6 months after RYGB-induced weight loss.

METHODS

The ribonucleic acid (RNA) of PBMCs from 13 obese women was analyzed before and 6 months after RYGB; the RNA of PBMCs from nine healthy women served as control. The gene expression levels were determined by microarray analysis. Significant differences in gene expression were validated by real-time quantitative polymerase chain reaction (RT-qPCR).

RESULTS

Microarray analysis for comparison of the pre- and postoperative periods showed that 1366 genes were differentially expressed genes (DEGs). The main pathways were related to gene transcription; lipid, energy, and glycide metabolism; inflammatory and immunological response; cell differentiation; oxidative stress regulation; response to endogenous and exogenous stimuli; substrate oxidation; mTOR signaling pathway; interferon signaling; mitogen-activated protein kinases (MAPK), cAMP response element binding protein (CREB1), heat shock factor 1 (HSF1), and sterol regulatory element binding protein 1c (SREBP-1c) gene expression; adipocyte differentiation; and methylation.

CONCLUSIONS

Six months after bariatric surgery and significant weight loss, many molecular pathways involved in obesity and metabolic diseases change. These findings are an important tool to identify potential targets for therapeutic intervention and clinical practice of nutritional genomics in obesity.

摘要

背景

Roux-en-Y胃旁路术(RYGB)后外周血单个核细胞(PBMC)中的基因差异表达特征尚不明确。这些过程的标志物可能有助于更深入地理解这些事件背后的机制。本研究的主要目的是确定肥胖女性在RYGB诱导体重减轻之前和之后6个月时PBMC基因表达的变化。

方法

分析了13名肥胖女性在RYGB术前和术后6个月时PBMC的核糖核酸(RNA);来自9名健康女性的PBMC的RNA作为对照。通过微阵列分析确定基因表达水平。基因表达的显著差异通过实时定量聚合酶链反应(RT-qPCR)进行验证。

结果

术前和术后时期比较的微阵列分析表明,有1366个基因是差异表达基因(DEG)。主要途径与基因转录、脂质、能量和糖类代谢、炎症和免疫反应、细胞分化、氧化应激调节、对内源和外源刺激的反应、底物氧化、mTOR信号通路、干扰素信号、丝裂原活化蛋白激酶(MAPK)、环磷酸腺苷反应元件结合蛋白(CREB1)、热休克因子1(HSF1)和固醇调节元件结合蛋白1c(SREBP-1c)基因表达、脂肪细胞分化和甲基化有关。

结论

减肥手术后6个月且体重显著减轻后,许多与肥胖和代谢性疾病相关的分子途径发生了变化。这些发现是确定肥胖症治疗干预潜在靶点以及营养基因组学临床实践的重要工具。

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