Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain.
Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
Obesity (Silver Spring). 2020 Sep;28(9):1708-1717. doi: 10.1002/oby.22902. Epub 2020 Jul 29.
The study aim was to identify changes in duodenal gene expression associated with the development of insulin resistance according to the BMI of women.
Duodenal samples were assessed by microarray in four groups of women, nonobese women and women with severe obesity, with both low and high insulin resistance.
There was a group of shared downregulated differentially expressed genes (DEGs) related to tissue homeostasis and antimicrobial humoral response in women with higher insulin resistance both with severe obesity and without obesity. In the exclusive DEGs found in severe obesity, downregulated DEGs related to the regulation of the defense response to bacterium and cell adhesion, involving pathways related to the immune system, inflammation, and xenobiotic metabolism, were observed. In the exclusive DEGs from nonobese women with higher insulin resistance, upregulated DEGs mainly related to the regulation of lipoprotein lipase activity, very low-density lipoprotein particle remodeling, lipid metabolic process, antigen processing, and the presentation of peptide antigen were found.
Independent of BMI, higher insulin resistance was associated with a downregulation of duodenal DEGs mainly related to the immune system, inflammation, and xenobiotic metabolism. Also, intestinal lipoprotein metabolism may have a certain relevance in the regulation of insulin resistance in nonobese women.
本研究旨在根据女性 BMI 识别与胰岛素抵抗发展相关的十二指肠基因表达变化。
通过微阵列分析了 4 组女性的十二指肠样本，分别是非肥胖女性和肥胖程度不同且胰岛素抵抗程度不同的两组女性。
在胰岛素抵抗较高的肥胖和非肥胖女性中，存在一组与组织稳态和抗菌体液反应相关的下调差异表达基因（DEGs）存在共享。在肥胖女性中发现的特异性 DEGs 中，下调的 DEGs 与对细菌的防御反应和细胞黏附的调节有关，涉及与免疫系统、炎症和异生物质代谢相关的途径。在胰岛素抵抗较高的非肥胖女性中发现的特异性 DEGs 中，上调的 DEGs 主要与脂蛋白脂肪酶活性的调节、极低密度脂蛋白颗粒重塑、脂质代谢过程、抗原加工和肽抗原呈递有关。
无论 BMI 如何，较高的胰岛素抵抗与十二指肠 DEGs 的下调有关，主要与免疫系统、炎症和异生物质代谢有关。此外，肠道脂蛋白代谢可能在非肥胖女性胰岛素抵抗的调节中具有一定的相关性。
