Zinc-α2-glycoprotein promotes browning of white adipose tissue in cold-exposed male mice
Zinc-α2-glycoprotein promotes browning of white adipose tissue in cold-exposed male mice
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锌-α2-糖蛋白促进冷暴露雄性小鼠白色脂肪组织褐变
DOI：
10.1016/j.mce.2019.110669
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发表时间：
2020-02-05
影响因子：
4.1
通讯作者：
Yang, Xiaojing
中科院分区：
文献类型：
--
作者：
Fan, Guoqiang;Dang, Xiaobo;Yang, Xiaojing
促进白色脂肪组织（WAT）布朗宁已经成为增加能量消耗和减少体重增加的有前景的治疗靶点。锌-α 2-糖蛋白（ZAG）是新近发现的一种调节脂质代谢的脂肪因子。它在棕色脂肪组织（BAT）中显示出高表达，但ZAG是否在白色脂肪组织的布朗宁中起关键作用仍在很大程度上不清楚。在本研究中，我们在冷暴露的ZAG敲除（KO）小鼠和ZAG过表达的3 T3-L1脂肪细胞中探索了ZAG与WAT布朗宁褐变的关系。结果表明，冷应激诱导野生型（WT）小鼠中ZAG的显著积累。此外，ZAG缺乏抑制冷应激小鼠体重和脂肪组织重量的损失。ZAG KO小鼠对冷诱导的布朗宁标记物表达和WAT中的能量代谢具有抗性。此外，补充ZAG质粒改善了ZAG KO小鼠中冷诱导的WAT布朗宁的减少。在体外，ZAG过表达促进布朗宁和线粒体生物合成，并增加β 3-AR和P-P38在3 T3-L1脂肪细胞中的表达。这些发现表明，ZAG可以促进白色脂肪组织的布朗宁，并且可以用作治疗代谢疾病如肥胖症的潜在治疗靶标。
The promotion of white adipose tissue (WAT) browning has emerged as a promising therapeutic target to increase energy expenditure and decrease weight gain. Zinc-alpha 2-glycoprotein (ZAG) is a newly identified adipokine that regulates lipid metabolism. It shows high expression in brown adipose tissue (BAT), but whether ZAG plays a key role in the browning of white adipose tissue is still largely unclear. In the present study, we explored the relationship between ZAG and the browning of WAT in cold-exposed ZAG knockout (KO) mice and 3T3-L1 adipocytes with overexpressed ZAG. The results showed that cold stress induced marked accumulation of ZAG in wild type (WT) mice. Additionally, ZAG deficiency inhibited the loss of body weight and adipose tissue weight in cold stressed mice. ZAG KO mice were resistant to cold-induced expression of browning markers and energy metabolism in WAT. Furthermore, replenishment ZAG plasmid improved the reduction in cold-induced browning of WAT in ZAG KO mice. In vitro, ZAG overexpression promoted browning and mitochondrial biogenesis and increased the expression of beta 3-AR and P-P38 in 3T3-L1 adipocytes. These findings demonstrate that ZAG can promote the browning of white adipose tissue and can serve as a potential therapeutic target for treating metabolic diseases such as obesity.