THE METABOLIC EFFECTS OF INTERLEUKIN-1-BETA ON HUMAN BONE-MARROW ADIPOCYTES

THE METABOLIC EFFECTS OF INTERLEUKIN-1-BETA ON HUMAN BONE-MARROW ADIPOCYTES
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DOI:
10.1006/cyto.1995.0043
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发表时间:
1995-05-01
期刊:
影响因子:
3.8
通讯作者:
ZUZEL, M
ZUZEL, M
中科院分区:
医学3区
文献类型:
--
作者:
DELIKAT, SE;GALVANI, DW;ZUZEL, M

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我们最近发现,白细胞介素1 β(IL-1 β)直接减少人骨髓(BM)基质细胞培养中脂肪细胞的数量。本研究的目的是建立参与这种IL-1效应的机制,从而评估其在BM病理生理学中的重要性。直接形态学观察显示,单个脂肪细胞在IL-1 β存在下失去脂肪,并在细胞因子撤出时重新获得脂肪。这些形态学观察结果得到了使用[(14)]乙酸盐作为储存脂肪前体的代谢研究的支持。这些代谢研究表明,IL-1 β抑制标记物掺入甘油三酯。此外,该细胞因子增强了预标记脂肪细胞的放射性释放,并减少了它们的甘油三酯储存。因此得出结论,IL-1 β可以抑制BM脂肪细胞中的脂肪生成并刺激脂肪分解。Forskolin(一种腺苷酸环化酶激活剂)产生的脂解作用与IL-1 β相似,而吲哚美辛(一种前列腺素[PG]生成抑制剂)完全阻断了IL-1 β诱导的放射性释放,并大大增加了甘油三酯合成。然而,IL-1 β在吲哚美辛存在下仍然能够减少甘油三酯合成。这些结果表明,cAMP中的一个依依地兰素的增加在IL-1 β的脂解作用中是重要的,但该细胞因子的抗脂肪生成作用至少部分地独立于PG合成。这些观察结果表明,IL-1 β的局部产生在调节BM储存脂肪代谢中具有潜在作用,其方式将有助于骨髓扩大其造血能力所需的能量。
We have recently shown that interleukin 1 beta (IL-1 beta) directly reduces the number of adipocytes in cultures of human bone marrow (BM) stromal cells. The aim of the present study was to establish the mechanisms involved in this IL-1 effect and thereby assess its importance in BM pathophysiology. Direct morphological observation showed that individual adipocytes lost their fat in the presence of IL-1 beta and regained it when the cytokine was withdrawn. These morphological observations were supported by metabolic studies using [(14)]acetate as a precursor of storage fat. These metabolic studies showed that IL-1 beta inhibited the incorporation of label into triglycerides. In addition, the cytokine enhanced the release of radioactivity from prelabelled adipocytes and reduced their triglyceride stores. It was therefore concluded that IL-1 beta can both inhibit Lipogenesis and stimulate lipolysis in BM adipocytes. Forskolin (an adenylate cyclase activator) produced lipolytic effects similar to those of IL-1 beta, while indomethacin (an inhibitor of prostaglandin [PG] production) fully blocked the release of radioactivity induced by IL-1 beta and greatly increased triglyceride synthesis. However, IL-1 beta was still able to decrease triglyceride synthesis in the presence of indomethacin. These results indicate that a prostaglandin-dependent increase in cAMP is important in the lipolytic effects of IL-1 beta but that the anti-lipogenic effects of the cytokine are, at least in part, independent of PG synthesis. These observations suggest that local production of IL-1 beta has a potential role in regulating BM storage fat metabolism in a way that would contribute to the energy required for the marrow's ability to expand its haematopoietic capacity.