Tayek J A
Department of Medicine, UCLA, School of Medicine, Harbor-UCLA Medical Center, Torrance, USA.
J Am Coll Nutr. 1996 Apr;15(2):164-8. doi: 10.1080/07315724.1996.10718583.
The present study was performed to determine the chronology of the effects of a single 50 ug subcutaneous dose of TNF on food intake, weight gain, and skeletal muscle protein metabolism in normal rats. Earlier work demonstrated that a single subcutaneous dose of 50 ug of tumor necrosis factor alpha (TNF) significantly increased skeletal muscle protein synthesis and breakdown in the tumor bearing rat [1]. Some of the earlier work demonstrated that TNF can reduce food intake, weight gain and enhance muscle catabolism.
Twenty-five male Sprague Dawley rats were randomized assigned to treatment or saline arms of the study. Rates of in vivo incorporation of L-1-14C-leucine into skeletal muscle were measured by the flooding dose technique. Rats were studied 6 and 60 hours after TNF or saline.
Six hours after administration of the TNF, the total skeletal muscle amino acid concentration was significantly reduced by 20%. The greatest reductions were seen in lysine, arginine, and isoleucine (39-53%) followed by serine, tyrosine, ornithine, threonine and alanine (18-32%). Despite this drop in skeletal muscle amino acid concentrations, the rate of skeletal muscle protein synthesis was similar to the controls (12.2 +/- 4.1 vs 13.8 +/- 3.7 %/day, mean +/- sd, saline vs TNF treated, respectively). Dietary intake (8.2 +/- 0.5 vs 7.3 +/- 1.1 g/day) and weight gain (7.1 +/- 1.1 vs 9.1 +/- 3.8 g/day) were not affected by TNF administration. However, there was a significant increase in skeletal muscle protein synthesis rate in the TNF treated group after 60 hours (17.8 +/- 4.0 vs 12.2 +/- 4.1 %/day) but not after 6 hours (13.8 +/- 3.7 vs 13.7 +/- 3.3 %/day) compared to saline treated rats, respectively. TNF administration after 60 hours was not associated with an elevated skeletal muscle 3-methyl-histidine concentration or a reduced nitrogen balance.
These data suggest that at a 50 ug subcutaneous dose of TNF, an early (6 hours) effect is to reduce skeletal muscle of amino acids without effecting either synthesis or breakdown. A later effect (60 hours) is to normalize skeletal muscle amino acid concentration and to increase skeletal muscle protein synthesis. This suggests that TNF may acutely alter amino acid transport as one of its modes of action.
本研究旨在确定皮下注射单次50微克肿瘤坏死因子（TNF）对正常大鼠食物摄入量、体重增加及骨骼肌蛋白质代谢影响的时间顺序。早期研究表明，皮下注射单次50微克肿瘤坏死因子α（TNF）可显著增加荷瘤大鼠骨骼肌蛋白质的合成与分解[1]。一些早期研究表明，TNF可减少食物摄入量、体重增加并增强肌肉分解代谢。
将25只雄性斯普拉格-道利大鼠随机分为研究的治疗组或生理盐水组。采用灌流剂量技术测定L-1-14C-亮氨酸在骨骼肌中的体内掺入率。在注射TNF或生理盐水后6小时和60小时对大鼠进行研究。
注射TNF后6小时，骨骼肌总氨基酸浓度显著降低了20%。赖氨酸、精氨酸和异亮氨酸降低最为明显（39 - 53%），其次是丝氨酸、酪氨酸、鸟氨酸、苏氨酸和丙氨酸（18 - 32%）。尽管骨骼肌氨基酸浓度有所下降，但骨骼肌蛋白质合成速率与对照组相似（分别为12.2±4.1%/天和13.8±3.7%/天，生理盐水组与TNF治疗组，平均值±标准差）。TNF给药未影响饮食摄入量（8.2±0.5克/天对7.3±1.1克/天）和体重增加（7.1±1.1克/天对9.1±3.8克/天）。然而，与生理盐水处理的大鼠相比，TNF治疗组在60小时后骨骼肌蛋白质合成速率显著增加（17.8±4.0%/天对12.2±4.1%/天），但在6小时后未增加（13.8±3.7%/天对13.7±3.3%/天）。60小时后给予TNF与骨骼肌3-甲基组氨酸浓度升高或氮平衡降低无关。
这些数据表明，皮下注射50微克TNF时，早期（6小时）效应是降低骨骼肌氨基酸含量，而不影响合成或分解。后期效应（60小时）是使骨骼肌氨基酸浓度恢复正常并增加骨骼肌蛋白质合成。这表明TNF可能作为其作用模式之一急性改变氨基酸转运。
