Tumor necrosis factor-alpha prevents the differentiation of human adipocyte precursor cells and causes delipidation of newly developed fat cells.
Tumor necrosis factor-alpha prevents the differentiation of human adipocyte precursor cells and causes delipidation of newly developed fat cells.
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DOI：
10.1210/jcem.76.3.8445033
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发表时间：
1993-03
期刊：
影响因子：
--
通讯作者：
T. Petruschke;Hans Hauner
中科院分区：
文献类型：
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作者：
T. Petruschke;Hans Hauner
我们研究了肿瘤坏死因子-α（TNF-α）对原代培养的人脂肪前体细胞分化的影响。脂肪细胞前体在化学成分确定的、补充脂肪酸的培养基中在12-16天内转化为脂肪细胞。培养的前脂肪细胞暴露于TNF α导致发育中的脂肪细胞数量和甘油-3-磷酸脱氢酶（GPDH）（脂肪细胞分化的既定标志物）的活性呈剂量和时间依赖性降低。与对照培养物相比，用浓度为5 nM的TNF α孵育24小时，可抑制55%的GPDH活性。细胞连续暴露于TNF α完全阻断了脂肪细胞表型和GPDH活性的表达。通过细胞计数评估，TNF α的抑制作用与细胞数量变化无关。向新形成的脂肪细胞中加入5 nM TNF α 24 h，导致GPDH活性迅速降低约50%。分化细胞暴露于TNF α 14天后，GPDH完全抑制，细胞明显脱脂，包括形态学变化，导致长梭形细胞质延伸的发展。这些结果清楚地表明，TNF α抑制人脂肪细胞前体细胞的分化，此外，促进成熟脂肪细胞的脱脂。这表明，TNF α可能参与人体脂肪组织细胞结构和功能的生理控制。
We investigated the effect of the tumor necrosis factor-alpha (TNF alpha) on the differentiation of human adipocyte precursor cells in primary culture. Adipocyte precursors convert into fat cells within 12-16 days in a chemically defined, hormone-supplemented medium. Exposure of cultured preadipocytes to TNF alpha resulted in a dose- and time-dependent decrease in the number of developing fat cells and the activity of glycerol-3-phosphate dehydrogenase (GPDH), an established marker of adipocyte differentiation. A 24-h incubation with TNF alpha at a concentration of 5 nM suppressed GPDH activity by 55% compared to that in control cultures. Continuous exposure of the cells to TNF alpha completely blocked expression of the adipocyte phenotype and GPDH activity. The inhibitory action of TNF alpha was not associated with a change in cell number, as assessed by cell counting. The addition of 5 nM TNF alpha for 24 h to newly developed fat cells caused a rapid reduction of GPDH activity by approximately 50%. A 14-day exposure of differentiated cells to TNF alpha was followed by complete suppression of GPDH and a marked delipidation of the cells, including morphological changes, leading to the development of long spindle-shaped cytoplasmatic extensions. These results clearly demonstrate that TNF alpha inhibits the differentiation of human adipocyte precursor cells and, in addition, promotes the delipidation of mature fat cells. It is suggested that TNF alpha may be involved in the physiological control of human adipose tissue cellularity and function.