The promotion of white adipose tissue (WAT) browning has emerged as a promising therapeutic target to increase energy expenditure and decrease weight gain. Zinc-α2-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 β3-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.

中文翻译：

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锌-α2-糖蛋白促进冷暴露的雄性小鼠中白色脂肪组织的褐变。

促进白色脂肪组织（WAT）褐变已成为一种有希望的治疗目标，以增加能量消耗并减少体重增加。锌-α2-糖蛋白（ZAG）是新近确定的调节脂质代谢的脂肪因子。它在棕色脂肪组织（BAT）中显示高表达，但是ZAG是否在白色脂肪组织的褐变中起关键作用仍然不清楚。在本研究中，我们探讨了ZAG与冷暴露ZAG基因敲除（KO）小鼠和ZAG过表达的3T3-L1脂肪细胞中WAT褐变之间的关系。结果表明，冷应激在野生型（WT）小鼠中诱导ZAG明显积累。另外，ZAG缺乏抑制了冷应激小鼠的体重和脂肪组织重量的损失。ZAG KO小鼠对WAT中冷诱导的褐变标记物表达和能量代谢具有抗性。此外，补充ZAG质粒改善了ZAG KO小鼠冷诱导WAT褐变的减少。在体外，ZAG过表达促进褐变和线粒体生物发生，并增加3T3-L1脂肪细胞中β3-AR和P-P38的表达。这些发现表明，ZAG可以促进白色脂肪组织的褐变，并且可以作为治疗肥胖等代谢性疾病的潜在治疗靶标。