Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors
Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors
复制标题
DOI：
10.2337/diabetes.51.6.1699
复制
发表时间：
2002-06-01
期刊：
影响因子：
7.7
通讯作者：
Sharma, AM
中科院分区：
文献类型：
--
作者：
Janke, J;Engeli, S;Sharma, AM
最近的研究表明，血管紧张素 II (Ang II) 在小鼠前脂肪细胞的脂肪生成中发挥作用。在这里，我们研究了 Ang II 在原代培养的人前脂肪细胞分化中的作用。从人类脂肪组织中分离出前脂肪细胞并刺激其分化。对脂肪生成过程中的肾素-血管紧张素系统（RAS）基因进行基因表达定量。通过向分化培养基中添加血管紧张素原 (AGT)、Ang II 或血管紧张素受体拮抗剂来研究 RAS 对脂肪形成分化的影响。我们还通过共培养实验研究了脂肪细胞对脂肪生成的影响。 RAS 基因 AGT、肾素、血管紧张素转换酶和 Ang It 1 型受体的表达在脂肪形成过程中增加。 Ang II 刺激 Ang II 1 型受体可减少脂肪转化，而阻断该受体则显着增强脂肪生成。脂肪细胞能够在共培养物中抑制前脂肪细胞分化，并且这种作用可以通过阻断 Ang II 1 型受体来消除。这一发现指出了 RAS 在人类脂肪组织分化中的功能作用。由于 AGT 分泌和 Ang II 生成是脂肪生成的特征，因此我们假设旁分泌负反馈回路会抑制成熟脂肪细胞进一步募集前脂肪细胞。
Recent studies suggest that angiotensin II (Ang II) plays a role in the adipogenesis of murine preadipocytes. Here, we examined the role of Ang II for the differentiation of primary cultured human preadipocytes. Preadipocytes were isolated from human adipose tissue and stimulated to differentiate. Quantitation of gene expression during adipogenesis was performed for renin-angiotensin system (RAS) genes. The influence of the RAS on adipogenic differentiation was investigated by addition of either angiotensinogen (AGT), Ang II, or angiotensin receptor antagonists to the differentiation medium. We also examined the influence of adipocytes on adipogenesis by co-culture experiments. Expression of the RAS genes AGT, renin, angiotensin-converting enzyme, and Ang It type 1 receptor increased during adipogenesis. Stimulation of the Ang II type 1 receptor by Ang II reduced adipose conversion, whereas blockade of this receptor markedly enhanced adipogenesis. Adipocytes were able to inhibit preadipocyte differentiation in the co-culture, and this effect was abolished by blockade of the Ang II type 1 receptor. This finding points to a functional role of the RAS in the differentiation of human adipose tissue. Because AGT secretion and Ang II generation are characteristic features of adipogenesis, we postulate a paracrine negative-feedback loop that inhibits further recruitment of preadipocytes by maturing adipocytes.