Jones B H, Kim J H, Zemel M B, Woychik R P, Michaud E J, Wilkison W O, Moustaid N
Department of Nutrition, University of Tennessee, Knoxville 37996-19, USA.
Am J Physiol. 1996 Jan;270(1 Pt 1):E192-6. doi: 10.1152/ajpendo.1996.270.1.E192.
Mutations leading to ectopic expression of the murine agouti gene (a) result in progressive obesity. To further characterize this model, we analyzed adipose and hepatic mRNA levels for fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD), two key enzymes in de novo fatty acid synthesis and desaturation, respectively. FAS and SCD mRNA in both tissues of obese (Avy) mice were dramatically increased relative to lean (ala) controls. Excessive expression of these genes in this model could be due to direct effects of the agouti gene product; to test this possibility we treated 3T3-L1 adipocytes in vitro with recombinant agouti protein. Agouti treatment increased FAS and SCD mRNA levels by 1.5- and 4-fold, respectively. In addition, FAS activity and triglyceride content were 3-fold higher in agoutitreated 3T3-L1 cells relative to controls; these effects were attenuated by simultaneous treatment with a calcium channel blocker (nitrendipine). These data demonstrate that the agouti protein can directly increase lipogenesis in adipocytes and suggest that these effects are mediated through an intracellular calcium-dependent mechanism.
导致小鼠刺鼠基因（a）异位表达的突变会导致进行性肥胖。为了进一步表征该模型，我们分析了脂肪酸合成酶（FAS）和硬脂酰辅酶A去饱和酶（SCD）在脂肪组织和肝脏中的mRNA水平，这两种酶分别是从头脂肪酸合成和去饱和过程中的关键酶。与瘦型（ala）对照相比，肥胖（Avy）小鼠这两种组织中的FAS和SCD mRNA显著增加。在该模型中这些基因的过度表达可能是由于刺鼠基因产物的直接作用；为了验证这种可能性，我们在体外用重组刺鼠蛋白处理3T3-L1脂肪细胞。刺鼠蛋白处理分别使FAS和SCD mRNA水平提高了1.5倍和4倍。此外，与对照相比，经刺鼠蛋白处理的3T3-L1细胞中FAS活性和甘油三酯含量高3倍；同时用钙通道阻滞剂（尼群地平）处理可减弱这些作用。这些数据表明，刺鼠蛋白可直接增加脂肪细胞中的脂肪生成，并提示这些作用是通过细胞内钙依赖性机制介导的。
