Department and Laboratory of Intensive Care Medicine, Katholieke Universiteit Leuven, Belgium.
Am J Respir Crit Care Med. 2010 Aug 15;182(4):507-16. doi: 10.1164/rccm.200909-1395OC. Epub 2010 May 4.
Critical illness is characterized by lean tissue wasting, whereas adipose tissue is preserved. Overweight and obese critically ill patients may have a lower risk of death than lean patients, suggestive of a protective role for adipose tissue during illness.
To investigate whether adipose tissue could protectively respond to critical illness by storing potentially toxic metabolites, such as excess circulating glucose and triglycerides.
We studied adipose tissue morphology and metabolic activity markers in postmortem biopsies of 61 critically ill patients and 20 matched control subjects. Adipose morphology was also studied in in vivo biopsies of 27 patients and in a rabbit model of critical illness (n = 22).
Adipose tissue from critically ill patients revealed a higher number and a smaller size of adipocytes and increased preadipocyte marker levels as compared with control subjects. Virtually all adipose biopsies from critically ill patients displayed positive macrophage staining. The animal model demonstrated similar changes. Glucose transporter levels and glucose content were increased. Glucokinase expression was up-regulated, whereas glycogen and glucose-6-phosphate levels were low. Acetyl CoA carboxylase protein and fatty acid synthase activity were increased. Hormone-sensitive lipase activity was not altered, whereas lipoprotein lipase activity was increased. A substantially increased AMP-activated protein kinase activity may play a crucial role.
Postmortem adipose tissue biopsies from critically ill patients displayed a larger number of small adipocytes in response to critical illness, revealing an increased ability to take up circulating glucose and triglycerides. Similar morphologic changes were present in vivo. Such changes may render adipose tissue biologically active as a functional storage depot for potentially toxic metabolites, thereby contributing to survival.
危重病的特征是瘦组织消耗，而脂肪组织得以保留。超重和肥胖的危重病患者的死亡率可能低于瘦患者，这表明脂肪组织在疾病过程中可能发挥保护作用。
研究脂肪组织是否通过储存潜在毒性代谢物（如过量循环葡萄糖和甘油三酯）来对危重病产生保护性反应。
我们研究了 61 例危重病患者和 20 例匹配对照患者的尸检活检标本中的脂肪组织形态和代谢活性标志物。还研究了 27 例患者的活组织检查中的脂肪形态和兔危重病模型（n=22）中的脂肪形态。
与对照组相比，危重病患者的脂肪组织中脂肪细胞数量更多、体积更小，前脂肪细胞标志物水平升高。几乎所有来自危重病患者的脂肪活检均显示巨噬细胞阳性染色。动物模型也表现出类似的变化。葡萄糖转运蛋白水平和葡萄糖含量增加。葡萄糖激酶表达上调，而糖原和葡萄糖-6-磷酸水平降低。乙酰辅酶 A 羧化酶蛋白和脂肪酸合酶活性增加。激素敏感脂肪酶活性没有改变，而脂蛋白脂肪酶活性增加。显著增加的 AMP 激活蛋白激酶活性可能发挥关键作用。
危重病患者的尸检脂肪组织活检显示，在危重病的情况下，出现了更多的小脂肪细胞，这表明其摄取循环葡萄糖和甘油三酯的能力增加。在体内也存在类似的形态变化。这些变化可能使脂肪组织作为潜在毒性代谢物的生物活性储存库发挥作用，从而有助于存活。
