Acute metabolic effects of human recombinant tumor necrosis factor beta in the rat.
Acute metabolic effects of human recombinant tumor necrosis factor beta in the rat.
复制标题
人重组肿瘤坏死因子β对大鼠的急性代谢作用。
DOI：
10.1007/bf02303808
复制
发表时间：
1994
影响因子：
3.7
通讯作者：
Brennan,MF
中科院分区：
文献类型：
--
作者：
Blumberg,D;Tsuburaya,A;Burt,M;Donner,DB;Brennan,MF
背景：癌性恶病质与宿主代谢的几种改变有关，包括低氨基酸血症和脂质生成（GLC）和脂解的增加。肿瘤坏死因子β（TNFβ）是一种由丝裂原活化的T淋巴细胞和几种癌细胞系释放的淋巴因子，可导致3 T3 L1脂肪细胞中脂解的增加。由于对TNFβ在体内的代谢效应知之甚少，我们研究了其在大鼠中的急性效应。方法：28只雄性Fischer大鼠腹腔注射TNFβ（250 μg/kg）或生理盐水（CTL），4 h后，获得分离的肝细胞（通过原位胶原酶肝灌注[n=12]）或收集主动脉血（n=16）。将肝细胞与10 mM丙氨酸（ALA）或10 mM乳酸盐（LAC）孵育，并测量葡萄糖产生。用线性回归法测定GLC速率（nmol葡萄糖/106个细胞/min）。测量血浆乳酸盐、葡萄糖、胰岛素和氨基酸（AA）（nmol/ml），数值表示为平均值± SEM。结果：TNFβ可使丙氨酸转化率（2.7± 0.5vs1.2 ± 0.2nmol葡萄糖/106个细胞/min，TNF vsCTL）增加130%，使乳酸转化率（7.5± 1.0vs4.6 ± 0.5nmol葡萄糖/106个细胞/min，TNF vsCTL）增加60%。TNF处理的大鼠血浆胰岛素水平为1.2± 0.2ng/ml，而CTL为1.1± 0.2ng/ml。TNF β处理组大鼠血清总氨基酸水平为3,175±111 nmol/ml，CTL组为3,190±103 nmol/ml。结论：TNFβ在体内可引起丙氨酸和乳酸的肝细胞增生，而血浆胰岛素和氨基酸水平无明显变化。
Background:Cancer cachexia is associated with several alterations in host metabolism, including hypoaminoacidemia and an increase in gluconeogenesis (GLC) and lipolysis. Tumor necrosis factor β (TNFβ), a lymphokine released by mitogen-activated T lymphocytes and several cancer cell lines, causes an increase in lipolysis in 3T3L1 adipocytes. Since little is known about the metabolic effects of TNFβ in vivo, we examined its acute effects in the rat.Methods:Twenty-eight male Fischer rats were injected intraperitoneally with TNFβ (250 µg/kg) or saline (CTL), and after 4 h, isolated hepatocytes were obtained (by in situ collagenase liver perfusion [n=12]) or aortic blood was collected (n=16). Hepatocytes were incubated with 10 mMalanine (ALA) or 10 mMlactate (LAC), and glucose production was measured. Rates of GLC (nmol glucose/106cells/min) were determined by linear regression. Plasma lactate, glucose, insulin, and amino acids (AA) (nmol/ml) were measured, and values were expressed as means ± SEM. Comparisons between groups were made by unpairedttest or Mann-WhitneyUtest, and significance was defined as p<0.05.Results:TNFβ caused a 130% increase in gluconeogenesis from alanine (2.7±0.5 vs 1.2±0.2 nmol glucose/106cells/min, TNF vs CTL), and a 60% increase from lactate (7.5±1.0 vs 4.6±0.5 nmol glucose/106cells/min, TNF vs CTL). Plasma insulin levels in TNF treated rats were 1.2±0.2 ng/ml compared to 1.1±0.2 ng/ml in CTL. Total amino acid levels in TNF treated rats were 3,175±111 nmol/ml compared to 3,190±103 nmol/ml in CTL.Conclusion:In vivo TNFβ causes an increase in hepatic gluconeogenesis from alanine and lactate with no change in plasma insulin or amino acids.