McAndrew P F
Surg Clin North Am. 1986 Oct;66(5):1003-12. doi: 10.1016/s0039-6109(16)44037-5.
Progressive weight loss and anorexia are frequent phenomena in cancer patients. Although cachexia is an expected occurrence in the terminal stages of nearly all malignancies, it may be a presenting sign when the tumor burden is quite small. Lipid depletion occurs out of proportion to the protein loss and accounts for most of the weight loss in cancer. Lipids, more specifically fatty acids, are the major source of fuel in mammals and may also be used in the synthesis of new cell products. Lipolysis and lipogenesis are under the influence of several important enzymes and peptide hormones that may be modulated by a variety of exogenous factors. There is evidence that cancer patients have lost the normal homeostatic responses to decreased energy intake or starvation that allow a decrease in oxygen consumption and protein sparing. An increase in Cori cycle activity or futile recycling of metabolic products occurs with a net energy expenditure rather than energy production. Clinical studies have shown that the body lipid depletion accompanying tumor progression is not solely secondary to decreased food intake and may be reproduced by the transplantation of certain noninvasive tumors to normal hosts. Elevated basal lipolysis has occasionally been seen early in tumor growth. Such findings suggest the presence of a tumor-associated factor responsible for this increase in lipid mobilization. Some of the potential mechanisms for the altered lipid metabolism seen in cancer have been discussed. Metabolic substrates may be remodeled and directed away from fuel-efficient into energy-requiring pathways. An increased energy expenditure may occur as a result of the energy costs of tumor synthesis, an uncoupling of oxidative phosphorylation, or energy-requiring futile cycling. An overall depletion of lipid may be the final outcome of the inhibition of lipid deposition. TNF/cachectin has recently been found to suppress the activity and synthesis of several key lipogenic enzymes, including lipoprotein lipase. Abnormalities in insulin secretion or sensitivity may be involved in the decrease of fat storage in malignancy. Insulin also exerts a significant antilipolytic effect by its antagonism of hormone-sensitive lipase. Mediators of lipolysis and abnormal lipid metabolism may occur in a number of clinical conditions and include ectopic hormone production, growth factors, and tumor-associated lipolytic factors (lipid mobilizing factor, toxohormone).
进行性体重减轻和厌食是癌症患者常见的现象。尽管恶病质在几乎所有恶性肿瘤的晚期都是预期会出现的情况，但当肿瘤负荷很小时，它也可能是首发症状。脂质消耗与蛋白质损失不成比例，且占癌症患者体重减轻的大部分。脂质，更具体地说是脂肪酸，是哺乳动物的主要能量来源，也可用于合成新的细胞产物。脂肪分解和脂肪生成受几种重要酶和肽激素的影响，这些酶和激素可能会受到多种外源性因素的调节。有证据表明，癌症患者已失去对能量摄入减少或饥饿的正常稳态反应，而这种反应可使氧气消耗减少并节省蛋白质。科里循环活性增加或代谢产物的无效循环会导致净能量消耗而非能量产生。临床研究表明，肿瘤进展伴随的身体脂质消耗并非仅仅继发于食物摄入量减少，并且可通过将某些非侵袭性肿瘤移植到正常宿主中来重现。在肿瘤生长早期偶尔会出现基础脂肪分解升高。这些发现表明存在一种与肿瘤相关的因素导致脂质动员增加。已经讨论了癌症中脂质代谢改变的一些潜在机制。代谢底物可能会被重塑，并从高效能途径转向需要能量的途径。由于肿瘤合成的能量消耗、氧化磷酸化的解偶联或需要能量的无效循环，可能会导致能量消耗增加。脂质的总体消耗可能是脂质沉积受抑制的最终结果。最近发现肿瘤坏死因子/恶病质素可抑制包括脂蛋白脂肪酶在内的几种关键脂肪生成酶的活性和合成。胰岛素分泌或敏感性异常可能与恶性肿瘤中脂肪储存减少有关。胰岛素还通过拮抗激素敏感性脂肪酶发挥显著的抗脂肪分解作用。脂肪分解和异常脂质代谢的介质可能出现在多种临床情况中，包括异位激素产生、生长因子和肿瘤相关的脂肪分解因子（脂质动员因子、毒激素）。
