Plomgaard Peter, Fischer Christian P, Ibfelt Tobias, Pedersen Bente K, van Hall Gerrit
Centre of Inflammation and Metabolism, Department of Infectious Diseases, Faculty of Health Sciences, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
J Clin Endocrinol Metab. 2008 Feb;93(2):543-9. doi: 10.1210/jc.2007-1761. Epub 2007 Nov 20.
Low-grade systemic inflammation is a feature of most lifestyle-related chronic diseases. Enhanced TNF-alpha concentrations have been implicated in the development of hyperlipidemia.
We hypothesized that an acute elevation of TNF-alpha in plasma would cause an increase in lipolysis, increasing circulatory free fatty acid (FFA) levels.
Using a randomized controlled, crossover design, healthy young male individuals (n = 10) received recombinant human (rh) TNF-alpha (700 ng/m(-2).h(-1)) for 4 h, and energy metabolism was evaluated using a combination of tracer dilution methodology and arterial-venous differences over the leg.
Plasma TNF-alpha levels increased from 0.7 +/- 0.04 to 16.7 +/- 1.8 pg/ml, and plasma IL-6 increased from 1.0 +/- 0.2 to 9.2 +/- 1.0 pg/ml (P < 0.05) after 4-h rhTNF-alpha infusion. Here, we demonstrate that 4-h rhTNF-alpha infusion increases whole body lipolysis by 40% (P < 0.05) with a concomitant increase in FFA clearance, with no changes in skeletal muscle FFA uptake, release, or oxidation. Of note, systemic glucose turnover and lactate and catecholamine levels were unaffected by rhTNF-alpha infusion.
This study demonstrates that a relatively low dose of rhTNF-alpha induces systemic lipolysis and that the skeletal muscle fat metabolism is unaffected.
低度全身炎症是大多数与生活方式相关的慢性疾病的一个特征。肿瘤坏死因子-α（TNF-α）浓度升高与高脂血症的发生有关。
我们假设血浆中TNF-α的急性升高会导致脂解增加，从而使循环游离脂肪酸（FFA）水平升高。
采用随机对照交叉设计，健康年轻男性个体（n = 10）接受重组人（rh）TNF-α（700 ng/m²·h⁻¹）静脉输注4小时，并结合示踪剂稀释法和腿部动静脉差评估能量代谢。
rhTNF-α输注4小时后，血浆TNF-α水平从0.7±0.04 pg/ml升高至16.7±1.8 pg/ml，血浆白细胞介素-6（IL-6）从1.0±0.2 pg/ml升高至9.2±1.0 pg/ml（P < 0.05）。在此，我们证明rhTNF-α输注4小时可使全身脂解增加40%（P < 0.05），同时FFA清除率增加，而骨骼肌FFA摄取、释放或氧化无变化。值得注意的是，rhTNF-α输注对全身葡萄糖周转率、乳酸和儿茶酚胺水平无影响。
本研究表明，相对低剂量的rhTNF-α可诱导全身脂解，且骨骼肌脂肪代谢不受影响。
