Adipokine zinc-α2-glycoprotein alleviates lipopolysaccharide-induced inflammatory responses through the β3-AR/PKA/CREB pathway
Adipokine zinc-α2-glycoprotein alleviates lipopolysaccharide-induced inflammatory responses through the β3-AR/PKA/CREB pathway
复制标题
脂肪因子锌-α2-糖蛋白通过 β3-AR/PKA/CREB 途径减轻脂多糖诱导的炎症反应
DOI：
10.1016/j.cyto.2019.154742
复制
发表时间：
2019-11-01
期刊：
影响因子：
3.8
通讯作者：
Yang, Xiaojing
中科院分区：
文献类型：
--
作者：
Guo, Jun;Li, Yanfei;Yang, Xiaojing
人类和动物经常经历由炎症引起的代谢异常。锌-α 2-糖蛋白（ZAG）是一种新发现的脂肪因子，可能参与脂质代谢。我们以前的研究表明，脂多糖（LPS）处理后，ZAG含量增加。为了阐明ZAG对炎症反应和脂质代谢的可能影响，我们使用基因过表达和基因敲除小鼠作为模型来研究ZAG在炎症过程中的功能。结果表明，脂多糖增加血浆甘油三酯，非酯化脂肪酸和肝脏甘油三酯，而ZAG过表达降低这些影响。此外，ZAG过表达减弱炎症反应，抑制脂肪生成，并改善炎症过程中的线粒体功能。ZAG过表达还增加β 3肾上腺素受体、蛋白激酶A和磷酸化环磷酸腺苷反应元件结合蛋白（CREB），促进CREB和CREB结合蛋白（CBP）的结合，并竞争性抑制核因子-κ B和CBP的结合。ZAG基因敲除后，LPS诱导的高脂血症加重。ZAG敲除加重炎症反应，促进脂肪生成，并削弱炎症过程中的线粒体功能。ZAG基因敲除也降低β 3肾上腺素受体和蛋白激酶A。本研究表明，ZAG通过减弱炎症反应减轻脂质代谢紊乱。β 3-肾上腺素受体/蛋白激酶A/CREB通路介导了ZAG对炎症的影响。这些结果将为抗炎研究提供新的思路。
Humans and animals frequently experience dysmetabolism induced by inflammation. Zinc-alpha 2-glycoprotein (ZAG), a newly identified adipokine, is potentially involved in lipid metabolism. Our previous study revealed that the ZAG content increased after lipopolysaccharide (LPS) treatment. To clarify ZAG's possible effects on inflammatory responses and lipid metabolism, we used gene overexpression and knockout mice as models to investigate the function of ZAG during inflammation. The results showed that LPS increased plasma triglyceride, non-esterified fatty acid and hepatic triglyceride, while ZAG overexpression decreased these effects. Furthermore, ZAG overexpression weakened inflammatory responses, suppressed lipogenesis, and improved mitochondrial function during inflammation. ZAG overexpression also increased beta 3-adrenoreceptor, protein kinase A, and phosphorylated cyclic adenosine monophosphate-response element binding protein (CREB), promoted the combination of CREB and CREB-binding protein (CBP), and competitively inhibited the combination of nuclear factor-kappa B and CBP. After ZAG knockout, LPS-induced the hyperlipidemia worsened. ZAG knockout aggravated inflammatory responses, promoted lipogenesis, and weakened mitochondrial function during inflammation. ZAG knockout also decreased beta 3-adrenoreceptor and protein kinase A. The present study demonstrated that ZAG alleviated lipid metabolism disorders by weakening inflammatory responses. The beta 3-adrenoreceptor/protein kinase A/CREB pathway mediated the effects of ZAG on inflammation. These results will provide new insight for research on anti-inflammation.