Russell S T, Tisdale M J
Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET, UK.
Prostaglandins Leukot Essent Fatty Acids. 2005 Jun;72(6):409-14. doi: 10.1016/j.plefa.2005.03.002.
Adipose tissue of mice bearing a cachexia-inducing murine tumour (MAC16) shows increased expression of zinc-alpha(2)-glycoprotein (ZAG), a lipolytic factor thought to be responsible for the increased lipolysis. The anti-cachectic agent eicosapentaenoic acid (EPA) (0.5 g/kg) attenuated the loss of body weight in mice bearing the MAC16 tumour, and this was accompanied by downregulation of ZAG expression in both white and brown adipose tissue, as determined by Western blotting. Glucocorticoids may be responsible for the increased ZAG expression in adipose tissue. Dexamethasone (1.68 microM) stimulated lipolysis in 3T3-L1 adipocytes, and this effect was attenuated by EPA (50 microM). In addition the lipolytic action of dexamethasone was attenuated by anti-ZAG antibody, suggesting that the induction of lipolysis was mediated through an increase in ZAG expression. This was confirmed by Western blotting, which showed that dexamethasone (1.68 microM) induced a two-fold increase in ZAG expression in both cells and media, and that this was attenuated by EPA (50 microM). These results suggest that EPA may preserve adipose tissue in cachectic mice by downregulation of ZAG expression through interference with glucocorticoid signalling.
携带可诱发恶病质的小鼠肿瘤（MAC16）的小鼠脂肪组织中，锌-α(2)-糖蛋白（ZAG）的表达增加，ZAG是一种脂解因子，被认为与脂解增加有关。抗恶病质药物二十碳五烯酸（EPA）（0.5 g/kg）减轻了携带MAC16肿瘤小鼠的体重减轻，且通过蛋白质免疫印迹法测定发现，白色和棕色脂肪组织中ZAG表达均下调。糖皮质激素可能是导致脂肪组织中ZAG表达增加的原因。地塞米松（1.68 microM）刺激3T3-L1脂肪细胞的脂解作用，而EPA（50 microM）可减弱这种作用。此外，抗ZAG抗体可减弱地塞米松的脂解作用，这表明脂解诱导作用是通过ZAG表达增加介导的。蛋白质免疫印迹法证实了这一点，其显示地塞米松（1.68 microM）使细胞和培养基中的ZAG表达增加了两倍，而EPA（50 microM）可减弱这种增加。这些结果表明，EPA可能通过干扰糖皮质激素信号传导下调ZAG表达，从而在恶病质小鼠中保护脂肪组织。
