Kralisch Susan, Klein Johannes, Lossner Ulrike, Bluher Matthias, Paschke Ralf, Stumvoll Michael, Fasshauer Mathias
University of Leipzig, Department of Internal Medicine III, 04103 Leipzig, Germany.
J Endocrinol. 2005 Jun;185(3):R1-8. doi: 10.1677/joe.1.06211.
Recently, visfatin was characterized as a novel adipo-cytokine that is upregulated in obesity and exerts insulin-mimetic effects in various tissues. To clarify expression and regulation of this adipocytokine, visfatin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction in 3T3-L1 adipocytes during adipogenesis and after treatment with various hormones known to alter insulin sensitivity. Visfatin expression was about 6-fold higher in 3T3-L1 adipocytes in vitro as compared with epididymal fat in vivo and increased during adipogenic conversion more than 3-fold. Interestingly, 100 nM dexamethasone significantly increased visfatin mRNA by almost 1.5-fold. In contrast, 500 ng/ml growth hormone (GH), 10 ng/ml tumor necrosis factor (TNF) alpha, and 10 microM isoproterenol downregulated visfatin expression by 45%, 36%, and 43% respectively. Insulin did not influence synthesis of this adipocytokine. The effects of dexamethasone, GH, TNFalpha and isoproterenol were time- and dose-dependent. Furthermore, activation of G(s)-protein-coupled pathways by forskolin and cholera toxin was sufficient to significantly downregulate visfatin mRNA. Taken together, our results show a differential regulation of visfatin mRNA by insulin resistance-inducing hormones, supporting the view that this adipo-cytokine might be an interesting novel candidate linking core components of the metabolic syndrome such as obesity and insulin resistance.
最近,内脂素被鉴定为一种新型脂肪细胞因子,在肥胖状态下上调,并在多种组织中发挥胰岛素模拟作用。为了阐明这种脂肪细胞因子的表达和调控机制,我们通过定量实时逆转录聚合酶链反应,检测了3T3-L1脂肪细胞在脂肪生成过程中以及用已知可改变胰岛素敏感性的各种激素处理后的内脂素mRNA水平。与体内附睾脂肪相比,体外培养的3T3-L1脂肪细胞中内脂素的表达约高6倍,并且在脂肪生成转化过程中增加了3倍以上。有趣的是,100 nM地塞米松可使内脂素mRNA显著增加近1.5倍。相反,500 ng/ml生长激素(GH)、10 ng/ml肿瘤坏死因子(TNF)α和10 μM异丙肾上腺素分别使内脂素表达下调45%、36%和43%。胰岛素不影响这种脂肪细胞因子的合成。地塞米松、GH、TNFα和异丙肾上腺素的作用具有时间和剂量依赖性。此外,福斯高林和霍乱毒素激活G(s)-蛋白偶联途径足以显著下调内脂素mRNA。综上所述,我们的结果表明胰岛素抵抗诱导激素对内脂素mRNA有不同的调控作用,支持了这种脂肪细胞因子可能是连接代谢综合征核心成分(如肥胖和胰岛素抵抗)的一个有趣的新候选因子的观点。