The calcium-sensing receptor promotes adipocyte differentiation and adipogenesis through PPARγ pathway
The calcium-sensing receptor promotes adipocyte differentiation and adipogenesis through PPARγ pathway
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钙敏感受体通过 PPARγ 途径促进脂肪细胞分化和脂肪生成
DOI：
10.1007/s11010-011-1118-5
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发表时间：
2012-02-01
影响因子：
4.3
通讯作者：
Sun, Chang-Hao
中科院分区：
文献类型：
--
作者：
He, Yong-Han;He, Ying;Sun, Chang-Hao
脂肪细胞分化和脂肪形成与肥胖及肥胖引起的代谢紊乱密切相关。据报道，钙敏感受体（CaSR）在人脂肪细胞中起抗脂溶作用，并在许多组织中调节细胞分化。然而，CaSR在脂肪细胞分化和脂肪形成中的作用尚未明确。在本研究中，我们观察到CaSR的激活显著促进了人SW872脂肪细胞的脂肪细胞分化和脂肪生成。基因表达分析显示，CaSR激活增加了转录因子增殖因子激活受体γ (PPAR γ)及其下游基因，包括CCAAT元件结合蛋白α (C/EBP α)、脂肪脂肪酸结合蛋白（aP2）和脂蛋白脂肪酶。CaSR刺激后，甘油-3-磷酸脱氢酶活性明显升高。此外，已经证明调节PPAR γ基因表达的环AMP和钙的水平受到CaSR激活的显著影响。这些作用可被CaSR小干扰RNA （CaSR- sirna）抑制。综上所述，我们的研究结果表明，激活CaSR可以促进脂肪细胞的分化和脂肪形成，这可能是通过上调PPAR γ及其下游基因的表达来实现的。因此，脂肪细胞中的CaSR可能通过促进脂肪细胞分化和脂肪形成参与了肥胖的发病机制。
Adipocyte differentiation and adipogenesis are closely related to obesity and obesity-induced metabolic disorders. The calcium-sensing receptor (CaSR) has been reported to play an antilipolytic role in human adipocyte and regulate cell differentiation in many tissues. However, the effects of CaSR on adipocyte differentiation and adipogenesis have not been clarified. In the study, we observed that activation of CaSR significantly promoted adipocyte differentiation and adipogenesis in human SW872 adipocytes. Gene expression analysis revealed that the CaSR activation increased the transcription factor proliferator-activated receptor gamma (PPAR gamma) and its downstream genes including CCAAT element binding protein alpha (C/EBP alpha), adipose fatty acid-binding protein (aP2), and lipoprotein lipase. The activity of glycerol-3-phosphate dehydrogenase was also increased after the stimulation of CaSR. In addition, levels of cyclic AMP and calcium which have been shown to regulate PPAR gamma gene expression were significantly affected by the activation of CaSR. These effects could be suppressed by CaSR small interfering RNA (CaSR-siRNA). In conclusion, our findings suggest that activation of CaSR promotes differentiation and adipogenesis in adipocytes, which might be achieved by upregulating PPAR gamma and its downstream gene expressions. Therefore, CaSR in adipocytes may be involved in the pathogenesis of obesity by promoting adipocyte differentiation and adipogenesis.