Mulligan H D, Tisdale M J
Pharmaceutical Sciences Institute, Aston University, Birmingham, U.K.
Biochem J. 1991 Jul 15;277 ( Pt 2)(Pt 2):321-6. doi: 10.1042/bj2770321.
Utilization of metabolic substrates in tumour and host tissues was determined in the presence or absence of two colonic tumours, the MAC16, which is capable of inducing cachexia in recipient animals, and the MAC13, which is of the same histological type, but without the effect on host body composition. Glucose utilization by different tissues was determined in vivo by the 2-deoxyglucose tracer technique. Glucose utilization by the MAC13 tumour was significantly higher than by the MAC16 tumour, and in animals bearing tumours of either type the tumour was the second major consumer of glucose after the brain. This extra demand for glucose was accompanied by a marked decrease in glucose utilization by the epididymal fat-pads, testes, colon, spleen, kidney and, in particular, the brain, in tumour-bearing animals irrespective of cachexia. The decrease in glucose consumption by the brain was at least as high as the metabolic demand by the tumour. This suggests that the tissues of tumour-bearing animals adapt to use substrates other than glucose and that alterations in glucose utilization are not responsible for the cachexia. Studies in vitro showed that brain metabolism in the tumour-bearing state was maintained by an increased use of lactate and 3-hydroxybutyrate, accompanied by a 50% increase in 3-oxoacid CoA-transferase. This was supported by studies in vivo which showed an increased metabolism of 3-hydroxybutyrate in tumour-bearing animals. Thus ketone bodies may be utilized as a metabolic fuel during the cancer-bearing state, even though the nutritional conditions mimic the fed state.
在存在或不存在两种结肠肿瘤的情况下，测定肿瘤和宿主组织中代谢底物的利用情况。这两种肿瘤分别是MAC16，它能够在受体动物中诱导恶病质；以及MAC13，它与MAC16具有相同的组织学类型，但对宿主体成分没有影响。通过2-脱氧葡萄糖示踪技术在体内测定不同组织的葡萄糖利用情况。MAC13肿瘤的葡萄糖利用率显著高于MAC16肿瘤，并且在患有任何一种类型肿瘤的动物中，肿瘤是仅次于大脑的第二大葡萄糖消耗者。对葡萄糖的这种额外需求伴随着附睾脂肪垫、睾丸、结肠、脾脏、肾脏，特别是大脑的葡萄糖利用率显著下降，在患有肿瘤的动物中，无论是否存在恶病质都是如此。大脑葡萄糖消耗的减少至少与肿瘤的代谢需求一样高。这表明患有肿瘤的动物组织适应使用葡萄糖以外的底物，并且葡萄糖利用的改变不是恶病质的原因。体外研究表明，在患有肿瘤的状态下，大脑代谢通过增加乳酸和3-羟基丁酸的利用来维持，同时3-氧代酸辅酶A转移酶增加50%。体内研究支持了这一点，该研究表明患有肿瘤的动物中3-羟基丁酸的代谢增加。因此，即使营养状况模拟进食状态，酮体在患有癌症的状态下也可能被用作代谢燃料。
