PREADIPOCYTE DIFFERENTIATION INVITRO - IDENTIFICATION OF A HIGHLY-ACTIVE ADIPOGENIC AGENT
PREADIPOCYTE DIFFERENTIATION INVITRO - IDENTIFICATION OF A HIGHLY-ACTIVE ADIPOGENIC AGENT
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DOI：
10.1002/jcp.1041340115
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发表时间：
1988-01-01
影响因子：
5.6
通讯作者：
MITSUI, H
中科院分区：
文献类型：
--
作者：
HIRAGUN, A;SATO, M;MITSUI, H
在体外脂肪转化系统中鉴定了高活性脂肪形成剂。该药物ADD 4743（或ADD）由Takeda Chemical Industries（Osaka）合成，是口服降糖药环格列酮的3-羟基衍生物，推测为后者的活性代谢产物。当用微摩尔浓度的ADD处理ST 13小鼠前脂肪细胞时，它们在细胞接种后8-11天内迅速且均匀地转化为脂质积累的脂肪细胞样细胞。ADD诱导的脂肪转化和脂质蓄积程度远远超过先前已知的诱导剂如吲哚美辛加胰岛素。用另外两种前脂肪细胞系（3 T3 L1和RMT大鼠前脂肪细胞）证实了ADD的高效成脂活性。除了成脂活性，ADD特异性抑制前脂肪细胞的细胞增殖。ADD的活性诱导脂质积累和ST 13细胞的生长抑制，表现出非常相似的剂量-反应关系。细胞增殖或三酰甘油含量的nonadipocytic间充质细胞或上皮细胞不受ADD。这些观察结果强烈表明，ADD诱导的生长抑制是不是由于药物的非特异性毒性，但与脂肪细胞特性的治疗细胞密切相关。目前的观察提供了证据表明，ADD将是一个强大的代理人在研究中，涉及前脂肪细胞分化。
A highly active adipogenic agent was identified in an in vitro adipose conversion system. This agent, ADD 4743 (or ADD), was synthesized by Takeda Chemical Industries (Osaka) as a 3-hydroxy derivative of an oral antidiabetic agent, ciglitazone, and has been presumed to be an active metabolite of the latter substances. When ST 13 mouse preadipose cells were treated with micromolar concentrations of ADD they rapidly and uniformly converted into lipid-accumulating adipocytelike cells within 8-11 days after cell seeding. The degree of adipose conversion and lipid accumulation induced by ADD far exceeded those of the previously known inducing agents such as indomethacin plus insulin. The highly potent adipogenic activity of ADD was confirmed with two other preadipose cell lines (3T3 L1 and RMT rat preadipose cells). In addition to adipogenic activity, ADD inhibited cell proliferation of preadipose cells specifically. Activity of ADD induced lipid accumulation and growth inhibition of ST 13 cells, exhibiting very similar dose-response relationships. Cell proliferation or triacylglycerol content of nonadipocytic mesenchymal cells or epithelial cells were not affected by ADD. These observations strongly suggest that ADD-induced growth inhibition is not due to the nonspecific toxicity of the drug but is tightly associated with the adipocytic character of the treated cells. The present observation provides evidence that ADD would be a powerful agent in studies that involve preadipocyte differentiation.