Center for Bioinformatics, EONE Laboratories , Incheon, Republic of Korea.
Department of Pharmacology, College of Medicine, Chung-Ang University , Seoul, Republic of Korea.
Adipocyte. 2020 Dec;9(1):576-586. doi: 10.1080/21623945.2020.1823140.
Regular exercise is the first line of therapy for treating obesity-mediated metabolic disorders, including insulin resistance. It has been reported that developmental endothelial locus-1 (DEL-1) enhances macrophage efferocytosis, resulting in inflammation clearance as well as improves insulin resistance in skeletal muscle. However, the relationship between exercise and DEL-1, and the effects of DEL-1 on insulin signalling in adipocytes have not been fully elucidated to date. Protein expression levels were determined by Western blot analysis. Cells were transfected with small interfering (si) RNA to suppress gene expression. Lipid accumulation levels were detected using Oil red-O staining. Proinflammatory cytokine secretion levels were measured using ELISA. DEL-1 expression levels were induced in the skeletal muscle of people who exercised using microarray analysis. Recombinant DEL-1 augmented AMP-activated protein kinase (AMPK) phosphorylation and haem oxygenase (HO)-1 expression to alleviating inflammation and impairment of insulin signalling in 3T3-L1 adipocytes treated with palmitate. siRNA of AMPK or HO-1 also mitigated the effects of DEL-1 on inflammation and insulin resistance. DEL-1 ameliorates inflammation and insulin resistance in differentiated 3T3-L1 cells via AMPK/HO-1 signalling, suggesting that DEL-1 may be the exercise-mediated therapeutic target for treating insulin resistance and type 2 diabetes.
规律运动是治疗肥胖相关代谢紊乱（包括胰岛素抵抗）的一线疗法。据报道，发育内皮定位-1（DEL-1）可增强巨噬细胞的胞饮作用，从而清除炎症并改善骨骼肌胰岛素抵抗。然而，运动与 DEL-1 之间的关系以及 DEL-1 对脂肪细胞胰岛素信号的影响尚未得到充分阐明。通过 Western blot 分析测定蛋白表达水平。用小干扰（si）RNA 转染细胞以抑制基因表达。用油红-O 染色检测脂质积累水平。用 ELISA 检测促炎细胞因子分泌水平。通过微阵列分析检测运动引起的人骨骼肌中 DEL-1 的表达水平。重组 DEL-1 增强了 3T3-L1 脂肪细胞中 AMP 激活的蛋白激酶（AMPK）磷酸化和血红素加氧酶（HO）-1 的表达，从而减轻了棕榈酸处理的脂肪细胞中的炎症和胰岛素信号受损。AMPK 或 HO-1 的 siRNA 也减轻了 DEL-1 对炎症和胰岛素抵抗的作用。DEL-1 通过 AMPK/HO-1 信号改善分化的 3T3-L1 细胞中的炎症和胰岛素抵抗，表明 DEL-1 可能是治疗胰岛素抵抗和 2 型糖尿病的运动介导的治疗靶点。
