Laboratório de Nutrição e Cirurgia Metabólica (LIM-35), Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; Laboratório de Carboidratos e Radioimunoensaio (LIM-18), Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; Programa de Pós-graduação em Medicina, Universidade Nove de Julho, São Paulo, Brazil.
Laboratório de Nutrição e Cirurgia Metabólica (LIM-35), Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
Nutrition. 2020 Nov-Dec;79-80:110885. doi: 10.1016/j.nut.2020.110885. Epub 2020 Jun 4.
Abnormal activation of toll-like receptors (TLRs) is observed in obese rodents and is correlated with local dysbiosis and increased gut permeability. These purported changes trigger systemic inflammation associated with obesity-related comorbidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for severe obesity and known to induce changes in the gut microbiota and decrease systemic inflammation in humans. This study examined the intestinal expression of TLR-encoding genes in obese women (n = 20) treated with RYGB surgery and the relationship of these genes with T2D remission (T2Dr METHODS: Intestinal biopsies were performed before and 3 months after RYGB surgery. Partial and complete T2Dr after 1 year was assessed using the American Diabetes Association criteria. Affymetrix Human GeneChip 1.0 ST array (microarray) and TaqMan assay (real-time quantitative polymerase chain reaction) were used to analyze intestinal gene expression, and associations with systemic markers of energy homeostasis were examined.
Patients experienced significant weight loss (P < 0.001) and altered gut TLR gene expression 3 months after surgery. The main effects were a reduction in jejunal TLR4 expression in patients with complete and partial T2Dr (P < 0.05). There was a postoperative decrease in jejunal TLR7 expression in patients with complete T2Dr that correlated inversely with high-density lipoprotein cholesterol and positively with triglyceride concentrations, but not with weight loss.
RYGB-induced weight loss-independent changes in the expression of intestinal TLR-encoding genes in obese women and complete T2Dr that was correlated with systemic markers of energy homeostasis. The modulation of intestinal TLRs may mediate inflammatory mechanisms linked to T2Dr after RYGB surgery.
肥胖啮齿动物中观察到 toll 样受体 (TLR) 的异常激活，与局部菌群失调和肠道通透性增加有关。这些所谓的变化会引发与肥胖相关的合并症相关的全身炎症，包括 2 型糖尿病 (T2D)。Roux-en-Y 胃旁路 (RYGB) 手术是治疗严重肥胖症的有效方法，已知可引起肠道微生物群的变化并降低人类的全身炎症。本研究检查了接受 RYGB 手术治疗的肥胖女性 (n = 20) 的肠道 TLR 编码基因表达，以及这些基因与 T2D 缓解 (T2Dr) 的关系。
在 RYGB 手术前和手术后 3 个月进行肠道活检。使用美国糖尿病协会标准评估 1 年后的部分和完全 T2Dr。使用 Affymetrix Human GeneChip 1.0 ST 阵列 (微阵列) 和 TaqMan 测定法 (实时定量聚合酶链反应) 分析肠道基因表达，并检查与全身能量稳态标志物的关联。
患者经历了显著的体重减轻 (P < 0.001) 和术后 3 个月肠道 TLR 基因表达的改变。主要影响是完全和部分 T2Dr 患者的空肠 TLR4 表达降低 (P < 0.05)。完全 T2Dr 患者术后空肠 TLR7 表达下降，与高密度脂蛋白胆固醇呈负相关，与甘油三酯浓度呈正相关，但与体重减轻无关。
RYGB 诱导肥胖女性肠道 TLR 编码基因表达的独立于体重减轻的变化和完全 T2Dr，与能量稳态的全身标志物相关。肠道 TLR 的调节可能介导与 RYGB 手术后 T2Dr 相关的炎症机制。
