Ferraz-Bannitz Rafael, Welendorf Caroline Rossi, Coelho Priscila Oliveira, Salgado Wilson, Nonino Carla Barbosa, Beraldo Rebeca A, Foss-Freitas Maria Cristina
Division of Endocrinology and Metabolism, Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo (USP), Avenida Bandeirantes, 3900-Vila Monte Alegre, Ribeirao Preto, SP, 14049-900, Brazil.
Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, SP, Brazil.
Diabetol Metab Syndr. 2021 Feb 16;13(1):19. doi: 10.1186/s13098-021-00623-w.
Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery.
We aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m) one day before surgery, 3 and 6 months (M) after RYGB.
Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3 M and 6 M Post-RYGB showed that interleukins [Interleukin 6, Tumor necrosis factor-α (TNF-α), and Monocyte chemoattractant protein-1(MCP1)] and endoplasmic reticulum stress (ERS) genes [Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)] decreased during the follow-up (P ≤ 0.01 for all). Otherwise, genes involved in energy homeostasis [Adiponectin and AMP-activated protein kinase (AMPK)], cellular response to oxidative stress [Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)], mitochondrial biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)] and amino acids metabolism [General control nonderepressible 2 (GCN2)] increased from baseline to all other time points evaluated (P ≤ 0.01 for all). Also, expression of Peroxisome proliferator-activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P < 0.05). Additionally, we observed that PGC1α, SIRT1 and AMPK strongly correlated to BMI at 3 M (P ≤ 0.01 for all), as well as ADIPOQ and SIRT1 to BMI at 6 M (P ≤ 0.01 for all).
Our findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB. Trial registration CAAE: 73,585,317.0.0000.5440.
减肥手术，尤其是胃旁路术（RYGB），是治疗重度肥胖最有效且持久的方法。涉及脂肪组织的机制可能对解释手术效果很重要。
我们旨在确定接受RYGB手术患者脂肪组织的基因特征。我们评估了13名肥胖且非糖尿病患者（平均年龄37岁，100%为女性，体重指数（BMI）为42.2kg/m²），分别在手术前一天、RYGB术后3个月和6个月进行评估。
将手术时采集的脂肪组织基因表达与RYGB术后3个月和6个月采集的样本进行比较分析，结果显示白细胞介素[白细胞介素6、肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白-1（MCP1）]和内质网应激（ERS）基因[真核翻译起始因子2α激酶3（EIF2AK3）和钙网蛋白（CALR）]在随访期间下降（所有P≤0.01）。此外，参与能量稳态的基因[脂联素和AMP激活的蛋白激酶（AMPK）]、细胞对氧化应激的反应[沉默调节蛋白1、沉默调节蛋白3和核因子红细胞2相关因子2（NRF2）]、线粒体生物发生[过氧化物酶体增殖物激活受体γ共激活因子1-α（PGC1α）]和氨基酸代谢[一般控制非抑制性2（GCN2）]从基线到所有其他评估时间点均增加（所有P≤0.01）。另外，RYGB术后过氧化物酶体增殖物激活受体γ（PPARϒ）（脂肪生成调节）的表达显著降低（P<0.05）。此外，我们观察到PGC1α、SIRT1和AMPK在3个月时与BMI密切相关（所有P≤0.01），ADIPOQ和SIRT1在6个月时与BMI密切相关（所有P≤0.01）。
我们的研究结果表明，体重减轻与脂肪组织炎症和ERS的改善以及对氧化应激的保护增加有关。这些观察结果与BMI的降低以及控制细胞能量稳态的关键基因密切相关，表明在RYGB术后热量限制和体重减轻期间，基因表达水平上存在一个适应性过程。试验注册号：CAAE：73,585,317.0.0000.5440。
