Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain.
Unidad de Gesti ón Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
Int J Obes (Lond). 2020 Feb;44(2):340-352. doi: 10.1038/s41366-019-0458-1. Epub 2019 Sep 25.
The intestinal immune response could play an important role in obesity-related comorbidities. We aim to study the profile of duodenal cytokines and chemokines in patients with morbid obesity (MO), its relation with insulin resistance (IR) and the intake of metformin, and with the evolution of MO after sleeve gastrectomy (SG).
Duodenal levels of 24 cytokines and 9 chemokines were analyzed in 14 nonobese and in 54 MO who underwent SG: with lower IR (MO-lower-IR), with higher IR (MO-higher-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM).
MO-lower-IR had higher levels of cytokines related to Th1, Th2, Th9, Th17, Th22, M1 macrophages, and chemokines involved in the recruitment of macrophages and T-lymphocytes (p < 0.05), and total (CD68 expression) and M1 macrophages (ITGAX expression) (p < 0.05) when compared with nonobese patients, but with a decrease in M2 macrophages (MRC1 expression) (p < 0.05). In MO-higher-IR, these chemokines and cytokines decreased and were similar to those found in nonobese patients. In MO-metf-T2DM, only IL-4 (Th2) and IL-22 (Th22) increased their levels with regard to MO-higher-IR (p < 0.05). In MO-higher-IR and MO-metf-T2DM, there was a decrease of CD68 expression (p < 0.05) while ITGAX and MRC1 were similar with regard to MO-lower-IR. We found an association between CXCL8, TNFβ and IL-2 with the evolution of body mass index (BMI) after SG (p < 0.05).
There is an association between a higher IR and a lower duodenal immune response in MO, with a slight increase in those patients with metformin treatment. Intestinal immune response could be involved in the evolution of BMI after SG.
肠道免疫反应可能在肥胖相关合并症中发挥重要作用。我们旨在研究病态肥胖（MO）患者十二指肠细胞因子和趋化因子的特征，及其与胰岛素抵抗（IR）和二甲双胍摄入的关系，以及袖状胃切除术（SG）后 MO 的演变。
分析了 14 名非肥胖者和 54 名接受 SG 的 MO 患者的十二指肠 24 种细胞因子和 9 种趋化因子水平：IR 较低（MO-低 IR）、IR 较高（MO-高 IR）和接受二甲双胍治疗的 2 型糖尿病（MO-metf-T2DM）。
MO-低 IR 患者的 Th1、Th2、Th9、Th17、Th22、M1 巨噬细胞相关细胞因子和参与巨噬细胞和 T 淋巴细胞募集的趋化因子水平较高（p<0.05），且总（CD68 表达）和 M1 巨噬细胞（ITGAX 表达）（p<0.05）高于非肥胖患者，但 M2 巨噬细胞（MRC1 表达）（p<0.05）下降。在 MO-高 IR 中，这些趋化因子和细胞因子减少，与非肥胖患者相似。在 MO-metf-T2DM 中，只有 IL-4（Th2）和 IL-22（Th22）与 MO-高 IR 相比增加了它们的水平（p<0.05）。在 MO-高 IR 和 MO-metf-T2DM 中，CD68 表达下降（p<0.05），而 ITGAX 和 MRC1 与 MO-低 IR 相似。我们发现 CXCL8、TNFβ 和 IL-2 与 SG 后体重指数（BMI）的演变之间存在关联（p<0.05）。
MO 中存在较高的 IR 与较低的十二指肠免疫反应相关，而接受二甲双胍治疗的患者则略有增加。肠道免疫反应可能参与了 SG 后 BMI 的演变。
