Lanza-Jacoby S, Lansey S C, Miller E E, Cleary M P
Cancer Res. 1984 Nov;44(11):5062-7.
The sequential changes in lipid metabolism during tumor growth were evaluated in inbred Lewis rats bearing a mammary adenocarcinoma (AC33). Serum lipids, insulin, glucagon, and liver and adipose tissue lipogenic enzymes were measured in tumor-bearing and control rats after 6, 12, 18, 24, and 32 days of tumor growth. Lipoprotein lipase (LPL) activity in heart, soleus muscle, and epididymal fat pads was also determined. On the sixth day, the activity of LPL was reduced in the adipose tissue and remained lower throughout the duration of the experiment. Serum triglycerides were elevated from the 12th day followed by an increase in free fatty acid levels from the 18th day of tumor growth. These changes were accompanied by a decrease in serum insulin levels in the tumor-bearing rats from Day 12. The presence of the tumor also decreased the activities of some of the lipogenic enzymes in liver and adipose tissue, but these changes occurred at the later time points. On the 24th day, a decrease in fat pad weights was found and characterized by a decrease in fat cell size but not in fat cell number. These results suggest that a defect in clearance, due to the decrease in the activity of adipose tissue LPL, may be responsible for the early development of hypertriglyceridemia during tumor growth. In this study, the alterations in the lipogenic enzymes and LPL cannot be attributed to reduced food intake but may be due to the direct or an indirect effect of the tumor on a hormone such as insulin.
在携带乳腺腺癌(AC33)的近交系Lewis大鼠中评估肿瘤生长过程中脂质代谢的顺序变化。在肿瘤生长6、12、18、24和32天后,测量荷瘤大鼠和对照大鼠的血清脂质、胰岛素、胰高血糖素以及肝脏和脂肪组织的脂肪生成酶。还测定了心脏、比目鱼肌和附睾脂肪垫中的脂蛋白脂肪酶(LPL)活性。在第6天,脂肪组织中LPL的活性降低,并且在整个实验期间一直保持较低水平。血清甘油三酯从第12天开始升高,随后从肿瘤生长第18天起游离脂肪酸水平升高。这些变化伴随着荷瘤大鼠从第12天起血清胰岛素水平的降低。肿瘤的存在还降低了肝脏和脂肪组织中一些脂肪生成酶的活性,但这些变化发生在较晚的时间点。在第24天,发现脂肪垫重量减轻,其特征是脂肪细胞大小减小而非脂肪细胞数量减少。这些结果表明,由于脂肪组织LPL活性降低导致的清除缺陷可能是肿瘤生长期间高甘油三酯血症早期发展的原因。在本研究中,脂肪生成酶和LPL的改变不能归因于食物摄入量减少,而可能是由于肿瘤对胰岛素等激素的直接或间接作用。