Wolfe R R, Shaw J H, Durkot M J
Prog Clin Biol Res. 1983;111:89-109.
There seems little doubt that there are signals for the increased mobilization of fat in shock, trauma, and sepsis. Whether those signals are reflected by an actual increase in mobilization is dependent on many variables including cardiovascular status. A hypothetical scheme based on our own experiments in the hyperdynamics phases of response to burn injury and to sepsis is presented in Figure 8. According to this scheme, catecholamines stimulate lipolysis in the adipose tissue, resulting in the release of glycerol and FFA into the plasma at increased rates. The glycerol is cleared by the liver and converted into glucose--a process stimulated by, among other things, glucagon. Some of the increased flux of FFA is also cleared by the liver, whereupon the fatty acids are incorporated into VLDL and released again into the plasma. The increased FFA levels also exert a dampening effect on the factors stimulating hepatic glucose production. At the periphery, plasma FFA as well as VLDL fatty acids are taken up at an increased rate. The tissues are attuned to the oxidation of fat, and as a consequence most of the energy production is derived from fat oxidation. The increased fatty acids exert an inhibitory effect on the complete oxidation of glucose, so although glucose may be taken up at an accelerated rate, the relative contribution of glucose oxidation to total energy production may fall. Rather than being completely oxidized, pyruvate is reduced to lactate and released into the plasma at an accelerated rate. The lactate then contributes to the production of glucose in the liver, completing a cyclical process called the Cori Cycle. Although all aspects of this scheme are supported by data highlighted in this paper, it certainly must be an oversimplification of the overall response of substrate metabolism to trauma and sepsis. It is presented for the purpose of highlighting the potential role of fat as a controller of the metabolic response, and to suggest that the enhanced mobilization and oxidation of fat is one of the fundamental responses to stress.
在休克、创伤和脓毒症中，脂肪动员增加似乎是毫无疑问的。这些信号是否反映为实际的动员增加取决于许多变量，包括心血管状态。图8展示了一个基于我们自身在烧伤和脓毒症反应的高动力阶段所做实验的假设方案。根据该方案，儿茶酚胺刺激脂肪组织中的脂肪分解，导致甘油和游离脂肪酸（FFA）以更快的速率释放到血浆中。甘油被肝脏清除并转化为葡萄糖——这一过程受到胰高血糖素等物质的刺激。部分增加的FFA通量也被肝脏清除，随后脂肪酸被整合到极低密度脂蛋白（VLDL）中并再次释放到血浆中。升高的FFA水平也会对刺激肝脏葡萄糖生成的因素产生抑制作用。在周围组织，血浆FFA以及VLDL脂肪酸的摄取速率增加。组织适应脂肪氧化，因此大部分能量产生来自脂肪氧化。增加的脂肪酸对葡萄糖的完全氧化产生抑制作用，所以尽管葡萄糖的摄取速率可能加快，但葡萄糖氧化对总能量产生的相对贡献可能下降。丙酮酸不是被完全氧化，而是被还原为乳酸并以更快的速率释放到血浆中。然后乳酸有助于肝脏中葡萄糖的生成，完成一个称为科里循环的循环过程。尽管该方案的所有方面都得到了本文所强调数据的支持，但它肯定是底物代谢对创伤和脓毒症总体反应的过度简化。提出该方案是为了突出脂肪作为代谢反应控制器的潜在作用，并表明脂肪动员和氧化的增强是对应激的基本反应之一。
