Fried S K, Zechner R
Laboratory of Human Behavior and Metabolism, Rockefeller University, New York, NY 10021.
J Lipid Res. 1989 Dec;30(12):1917-23.
The effects of the cytokine cachectin/tumor necrosis factor (TNF) on human adipose tissue lipoprotein lipase (LPL) were studied. TNF is produced by activated macrophages and is thought to play a role in mediating hypertriglyceridemia and wasting of adipose tissue triglyceride stores (cachexia) that often accompany infection and malignancy. TNF effects were studied in human adipose tissue fragments maintained in organ culture in the presence of insulin and dexamethasone to induce high LPL activity. Addition of TNF to the culture medium for 20 h caused a dose-dependent inhibition of LPL activity to an average of 37% of controls at 50 U/ml TNF. This inhibition of LPL activity was explained by specific decreases in levels of LPL mRNA (to 40% of controls) and rates of LPL synthesis determined by biosynthetic labeling and immunoprecipitation (to 32% of controls). The decline in LPL synthesis was specific, as it occurred despite a small increase in overall protein synthesis in the presence of TNF. Comparable decreases in LPL activity were observed when TNF was added to adipose tissue cultured solely in the presence of insulin. Thus, similar to results in rodent models, TNF is a potent inhibitor of LPL gene expression in human adipose tissue. TNF may therefore play a role in the disorders of triglyceride catabolism and the pathogenesis of cachexia that occur with stimulation of the immune system in humans.
研究了细胞因子恶病质素/肿瘤坏死因子（TNF）对人脂肪组织脂蛋白脂肪酶（LPL）的影响。TNF由活化的巨噬细胞产生，被认为在介导高甘油三酯血症以及常伴随感染和恶性肿瘤出现的脂肪组织甘油三酯储存消耗（恶病质）中起作用。在存在胰岛素和地塞米松以诱导高LPL活性的器官培养中维持的人脂肪组织片段中研究了TNF的作用。向培养基中添加TNF 20小时导致LPL活性呈剂量依赖性抑制，在50 U/ml TNF时平均降至对照的37%。LPL活性的这种抑制可通过LPL mRNA水平的特异性降低（降至对照的40%）以及通过生物合成标记和免疫沉淀测定的LPL合成速率（降至对照的32%）来解释。LPL合成的下降是特异性的，因为尽管在存在TNF的情况下总蛋白质合成略有增加，但它仍然发生。当TNF添加到仅在胰岛素存在下培养的脂肪组织中时，观察到LPL活性有类似的降低。因此，与啮齿动物模型中的结果相似，TNF是人类脂肪组织中LPL基因表达的有效抑制剂。因此，TNF可能在人类免疫系统受刺激时发生的甘油三酯分解代谢紊乱和恶病质发病机制中起作用。
