Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, P.R. China.
Appl Physiol Nutr Metab. 2019 Jan;44(1):83-89. doi: 10.1139/apnm-2018-0165. Epub 2018 Jul 4.
Zinc-α2-glycoprotein (ZAG) has been demonstrated to play a role in stimulating lipid mobilization under normal conditions. However, further studies are required to determine whether ZAG overexpression can alleviate the reduction in plasma lipid levels under stress conditions. In the present study, we investigated the effects of ZAG on lipometabolism in white adipose tissue (WAT) after dexamethasone (DEX) stimulation using C57BL/6 male mice as the experimental models. Transcript and protein levels of genes associated with the β-adrenoreceptor (β-AR)/cyclic adenosine monophosphate/protein kinase a (PKA) pathway, lipid mobilization, and energy metabolism were determined by quantitative real-time polymerase chain reaction and Western blotting. Plasma levels of nonesterified fatty acid (NEFA) were measured using an automatic biochemical analyzer. Results indicated that plasma NEFA levels were decreased in the DEX group, but NEFA levels were rescued by ZAG overexpression. ZAG overexpression resulted in the upregulation of β3-AR and phosphorylated PKA protein relative to those of the DEX group. Analysis of lipometabolism showed that protein levels of phosphorylated hormone-sensitive lipase was reduced upon DEX treatment but were restored by ZAG overexpression. For energy metabolism, ZAG significantly upregulated the protein expression of carnitine palmitoyltransferase1a and cytochrome c oxidase subunit 1 relative to those of the DEX group. In conclusion, ZAG could alleviate DEX-induced decrease in plasma NEFA levels and this could be associated with the promoting lipid mobilization in WAT.
锌-α2-糖蛋白（ZAG）已被证明在正常情况下在刺激脂质动员中发挥作用。然而，需要进一步的研究来确定 ZAG 过表达是否可以减轻应激条件下血浆脂质水平的降低。在本研究中，我们使用 C57BL/6 雄性小鼠作为实验模型，研究了 ZAG 在地塞米松（DEX）刺激后白色脂肪组织（WAT）中的脂代谢的影响。通过定量实时聚合酶链反应和 Western 印迹法测定与β-肾上腺素能受体（β-AR）/环磷酸腺苷/蛋白激酶 A（PKA）途径、脂质动员和能量代谢相关的基因的转录和蛋白水平。使用自动生化分析仪测量血浆中非酯化脂肪酸（NEFA）水平。结果表明，DEX 组血浆 NEFA 水平降低，但 ZAG 过表达可挽救 NEFA 水平。ZAG 过表达导致β3-AR 和磷酸化 PKA 蛋白的相对表达水平高于 DEX 组。脂代谢分析表明，DEX 处理后激素敏感脂肪酶的磷酸化蛋白水平降低，但 ZAG 过表达可恢复其水平。对于能量代谢，ZAG 显著上调肉碱棕榈酰转移酶 1a 和细胞色素 c 氧化酶亚基 1 的蛋白表达，高于 DEX 组。综上所述，ZAG 可以减轻 DEX 诱导的血浆 NEFA 水平降低，这可能与促进 WAT 中的脂质动员有关。
