ABSTRACT

Dysfunction of adipose tissue could lead to insulin resistance, obesity and type 2 diabetes. Thus, our present study aimed to investigate metabolites alterations in white adipose tissue (WAT) of diabetic GK rats after IT surgery. Ten-week-old male diabetic GK rats were randomly subjected to IT and Sham-IT surgery. Six weeks later, the untargeted metabolomics in WAT of diabetic GK rats was performed. Differential metabolites were selected according to the coefficient of variation (CV) of quality control (QC) sample <30%, variable importance in the projection (VIP) >1 and P < 0.05. Then, the hierarchical clustering of differential metabolites was conducted and the KEGG database was used for metabolic pathway analysis. A total of 50 (in positive ion mode) and 68 (in negative ion mode) metabolites were identified as differential metabolites in WAT of diabetic GK rats between IT group and Sham-IT group, respectively. These differential metabolites were well clustered, which in descending order of the number of involved differential metabolites is ubiquinone and other terpenoid-quinone biosynthesis, AMPK signalling pathway, pantothenate and CoA biosynthesis, ferroptosis, vitamin digestion and absorption, glycerophospholipid metabolism, phenylalanine metabolism, steroid hormone biosynthesis, neuroactive ligand–receptor interaction, porphyrin and chlorophyll metabolism and bile secretion, and correlated with the parameters of body weight, food intake, WAT mass and glucose metabolism, which were significantly improved after IT surgery. The differential metabolites in WAT of diabetic GK rats were mainly related to the pathway of energy metabolism, and correlated with the improved phenotypes of diabetic GK rats after IT surgery.

摘要

脂肪组织功能障碍可能导致胰岛素抵抗、肥胖和 2 型糖尿病。因此，我们目前的研究旨在调查 IT 手术后糖尿病 GK 大鼠白色脂肪组织 (WAT) 的代谢物变化。十周龄雄性糖尿病 GK 大鼠随机接受 IT 和假手术。六周后，在糖尿病 GK 大鼠的 WAT 中进行了非靶向代谢组学。根据质量控制 (QC) 样品的变异系数 (CV) <30%、投影中的变量重要性 (VIP) >1 和 P < 0.05，选择差异代谢物。然后，进行差异代谢物的层次聚类，并使用KEGG数据库进行代谢途径分析。IT组和Sham-IT组糖尿病GK大鼠WAT共鉴定出50种（正离子模式）和68种（负离子模式）代谢物作为差异代谢物。这些差异代谢物聚类较好，参与差异代谢物的数量从高到低依次为泛醌和其他萜类-醌生物合成、AMPK信号通路、泛酸和辅酶A生物合成、铁死亡、维生素消化和吸收、甘油磷脂代谢、苯丙氨酸代谢、类固醇激素生物合成、神经活性配体-受体相互作用、卟啉和叶绿素代谢以及胆汁分泌，并与体重、食物摄入量、WAT 质量和葡萄糖代谢等参数相关，这些参数在 IT 手术后得到显着改善。