Sakurai Y, Zhang X U, Wolfe R R
Metabolism Unit, Shriners Burns Institute, Galveston, TX 77555-1220.
J Clin Invest. 1993 Jun;91(6):2437-45. doi: 10.1172/JCI116478.
In vivo short-term effects of recombinant human TNF-alpha on lipolysis, FFA flux, fat oxidation, triglyceride-fatty acid cycling, and glucose kinetics were evaluated with stable isotopic tracers and indirect calorimetry along with monitoring of hemodynamic parameters in fasted dogs. High-dose TNF infusion (10 micrograms/kg) caused a fall in mean arterial pressure (P < 0.01), pulmonary arterial pressure (P < 0.001), and cardiac index (CI) (P < 0.05). The rate of appearance of glycerol (Ra glycerol) and the rate of appearance of FFA (Ra FFA) were decreased by 20% (P < 0.05) and by 42% (P < 0.01), respectively. Total fat oxidation fell by 23% (P < 0.05). In contrast, TNF infusion significantly increased glucose production by 13% (P < 0.05) and metabolic clearance rate of glucose by 25% (P < 0.01). However, TNF infusion did not change energy expenditure. Low-dose TNF infusion (3.5 micrograms/kg) caused changes similar in all respects, except magnitude, to the high-dose effects. There was a significant correlation between percent change of CI (delta CI) and percent change of rate of appearance of palmitate (Ra palmitate; delta Ra palmitate) (P < 0.0001, r = 0.69), Ra FFA (delta Ra FFA) (P < 0.0001, r = 0.60), and Ra glycerol (delta Ra glycerol) (P < 0.0329, r = 0.36). The correlation between delta CI and delta Ra palmitate was greater than the correlation between delta CI and delta Ra glycerol (P = 0.028). We conclude that the acute response to TNF causes a shift towards carbohydrate as an energy substrate in a dose-dependent manner by both decreasing the availability of FFAs and increasing glucose production.
在禁食犬中，使用稳定同位素示踪剂和间接量热法，并监测血流动力学参数，评估重组人肿瘤坏死因子-α（TNF-α）对脂解、游离脂肪酸（FFA）通量、脂肪氧化、甘油三酯-脂肪酸循环和葡萄糖动力学的体内短期影响。高剂量TNF输注（10微克/千克）导致平均动脉压下降（P<0.01）、肺动脉压下降（P<0.001）和心脏指数（CI）下降（P<0.05）。甘油的出现率（Ra甘油）和FFA的出现率（Ra FFA）分别降低了20%（P<0.05）和42%（P<0.01）。总脂肪氧化下降了23%（P<0.05）。相反，TNF输注使葡萄糖生成显著增加13%（P<0.05），葡萄糖代谢清除率增加25%（P<0.01）。然而，TNF输注并未改变能量消耗。低剂量TNF输注（3.5微克/千克）在所有方面引起的变化与高剂量效应相似，只是程度不同。CI的变化百分比（δCI）与棕榈酸出现率的变化百分比（Ra棕榈酸；δRa棕榈酸）（P<0.0001，r=0.69）、Ra FFA（δRa FFA）（P<0.0001，r=0.60）和Ra甘油（δRa甘油）（P<0.0329，r=0.36）之间存在显著相关性。δCI与δRa棕榈酸之间的相关性大于δCI与δRa甘油之间的相关性（P=0.028）。我们得出结论，TNF的急性反应通过降低FFA的可用性和增加葡萄糖生成，以剂量依赖的方式导致能量底物向碳水化合物转移。
