Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, UK.
J Endocrinol. 2010 Feb;204(2):165-72. doi: 10.1677/JOE-09-0299. Epub 2009 Nov 24.
Zinc-alpha2-glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested as a potential candidate in the modulation of body weight. We investigated the effect of increased adiposity on ZAG expression in adipose tissue and the liver and on plasma levels in obese (ob/ob) mice compared with lean siblings. The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) on ZAG expression in adipocytes. Zag mRNA levels were significantly reduced in subcutaneous (fourfold) and epididymal (eightfold) fat of ob/ob mice. Consistently, ZAG protein content was decreased in both fat depots of ob/ob mice. In the liver of obese animals, steatosis was accompanied by the fall of both Zag mRNA (twofold) and ZAG protein content (2.5-fold). Plasma ZAG levels were also decreased in obese mice. In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese (fa/fa) Zucker rats. In contrast to Zag expression, Tnfalpha mRNA levels were elevated in adipose tissue (twofold) and the liver (2.5-fold) of ob/ob mice. Treatment with TNFalpha reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFalpha treatment. It is concluded that ZAG synthesis in adipose tissue and the liver is downregulated, as are its circulating levels, in ob/ob mice. The reduced ZAG production may advance the susceptibility to lipid accumulation in these tissues in obesity, and this could be at least in part attributable to the inhibitory effect of TNFalpha.
锌-α2 糖蛋白（ZAG，在 MGI 数据库中也被列为 AZGP1）是一种脂质动员因子，最近被认为是调节体重的潜在候选物质。我们研究了肥胖（ob/ob）小鼠脂肪组织和肝脏中 ZAG 表达的增加以及血浆水平的变化，并与瘦型同窝仔鼠进行了比较。该研究还观察了促炎细胞因子肿瘤坏死因子-α（TNFalpha）对脂肪细胞中 ZAG 表达的影响。ob/ob 小鼠的皮下（四倍）和附睾（八倍）脂肪中 Zag mRNA 水平显著降低。一致地，ob/ob 小鼠的这两个脂肪组织中 ZAG 蛋白含量也降低了。肥胖动物的肝脏中，脂肪变性伴随着 Zag mRNA（两倍）和 ZAG 蛋白含量（2.5 倍）的下降。肥胖小鼠的血浆 ZAG 水平也降低了。此外，ob/fa 肥胖 Zucker 大鼠的附睾（五倍）和腹膜后（五倍）脂肪组织中 Zag mRNA 也减少了。与 Zag 表达相反，TNFalpha mRNA 水平在 ob/ob 小鼠的脂肪组织（两倍）和肝脏（2.5 倍）中升高。TNFalpha 处理降低了分化的脂肪细胞中 Zag 基因的表达，这种抑制是慢性的，在 TNFalpha 处理后 24 和 48 小时发生。因此，ob/ob 小鼠的脂肪组织和肝脏中 ZAG 的合成以及其循环水平均下调。这种 ZAG 产生的减少可能会增加这些组织中脂肪堆积的易感性，而这至少部分归因于 TNFalpha 的抑制作用。
