Adrenomedullin ameliorates palmitic acid-induced insulin resistance through PI3K/Akt pathway in adipocytes
Adrenomedullin ameliorates palmitic acid-induced insulin resistance through PI3K/Akt pathway in adipocytes
复制标题
DOI：
10.1007/s00592-021-01840-5
复制
发表时间：
2022-01-03
影响因子：
3.8
通讯作者：
Zhou, Ye-Bo
中科院分区：
文献类型：
--
作者：
Dai, Hang-Bing;Wang, Hong-Yu;Zhou, Ye-Bo
白色脂肪组织（WAT）功能障碍与脂肪组织轻度炎症和氧化应激相关，导致胰岛素抵抗（IR）。肾上腺髓质素（ADM）是一种内源性脂肪因子，与脂肪细胞的功能密切相关。方法观察ADM对软脂酸（PA）处理的3 T3-L1脂肪细胞和高脂饮食喂养的肥胖大鼠内脏白色脂肪组织（vWAT）IR的保护作用。结果经PA处理后的脂肪细胞内源性ADM及其受体蛋白表达明显增加。PA通过影响磷脂酰肌醇3-激酶（PI 3 K）-蛋白激酶B（Akt）轴和葡萄糖转运蛋白4（GLUT-4）水平，显著损伤胰岛素信号传导，而ADM预处理增强胰岛素信号传导PI 3 K/Akt和GLUT-4膜蛋白水平，降低促炎细胞因子肿瘤坏死因子α（TNF-α）水平。（TNF α）、白细胞介素-1 β（IL-1 β）和IL-6水平，以及改善的氧化应激，伴随着降低的活性氧（ROS）水平和增加的抗氧化酶锰超氧化物歧化酶2（SOD 2），谷胱甘肽过氧化物酶（GPx 1）和过氧化氢酶（CAT）蛋白表达。此外，ADM治疗不仅改善了肥胖大鼠的IR，而且有效地恢复了肥胖大鼠vWAT中的胰岛素信号传导，减轻了炎症和氧化应激。结论ADM对脂肪细胞的IR、炎症和氧化应激具有保护作用，对肥胖相关代谢紊乱具有预防作用。
Aims White adipose tissue (WAT) dysfunction has been associated with adipose tissue low-grade inflammation and oxidative stress leading to insulin resistance (IR). Adrenomedullin (ADM), an endogenous active peptide considered as an adipokine, is associated with adipocytes function. Methods We evaluated the protective effects of ADM against IR in 3T3-L1 adipocytes treated by palmitic acid (PA) and in visceral white adipose tissue (vWAT) of obese rats fed with high-fat diet. Results We found that endogenous protein expressions of ADM and its receptor in PA-treated adipocytes were markedly increased. PA significantly induced impaired insulin signaling by affecting phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) axis and glucose transporter-4 (GLUT-4) levels, whereas ADM pretreatment enhanced insulin signaling PI3K/Akt and GLUT-4 membrane protein levels, decreased pro-inflammatory cytokines tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and IL-6 levels, and improved oxidative stress accompanied with reduced reactive oxygen species (ROS) levels and increased anti-oxidant enzymes manganese superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx1) and catalase (CAT) protein expressions. Furthermore, ADM treatment not only improved IR in obese rats, but also effectively restored insulin signaling, and reduced inflammation and oxidative stress in vWAT of obese rats. Conclusions This study demonstrates a prevention potential of ADM against obesity-related metabolic disorders, due to its protective effects against IR, inflammation and oxidative stress in adipocytes.