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牛磺酸氯胺通过抑制分化的人脂肪细胞中的 STAT-3 信号通路来调节脂肪因子的表达。

Taurine chloramine modulates the expression of adipokines through inhibition of the STAT-3 signaling pathway in differentiated human adipocytes.

机构信息

East-West Bone and Joint Research Institute, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, 134-727, Republic of Korea,

出版信息

Amino Acids. 2013 Dec;45(6):1415-22. doi: 10.1007/s00726-013-1612-z. Epub 2013 Nov 1.

Abstract

To examine the possible role of taurine chloramine (TauCl) in modulating the expression of adipokines in adipose tissue associated with obesity, we evaluated the effect of TauCl in human differentiated adipocytes in response to IL-1β. To study the physiological effects of TauCl on adipokine expression, differentiated adipocytes were treated with IL-1β in the presence or absence of TauCl at concentrations ranging from 200 to 600 μM for 7 days. Cell culture supernatants and total RNA were analyzed by ELISA and real-time PCR, respectively, to determine protein and mRNA levels of adipokines, including adiponectin, leptin, IL-6, and IL-8. Levels of proteins involved in relevant signaling pathways were investigated by western blotting. Stimulation with IL-1β significantly decreased levels of adiponectin and leptin in adipocytes, but increased levels of IL-6 and IL-8 in a dose-dependent manner. Treatment with TauCl significantly reversed the modulation of adipokine expression by inhibiting STAT-3 signaling in IL-1β-stimulated adipocytes, independent of MAPK signaling. TauCl treatment more significantly modulated the expression of adipokines in adipocytes stimulated with IL-1β than that of non-stimulated adipocytes, suggesting that TauCl plays a significant role in modulating the expression of adipokines under inflammatory conditions. In conclusion, TauCl and other taurine derivatives that inhibit the STAT-3 signaling pathway can modulate expression of adipokines and thus may be useful as therapeutic agents for obesity-related diseases.

摘要

为了研究牛磺酸氯胺(TauCl)在调节肥胖相关脂肪组织中脂肪因子表达方面的可能作用,我们评估了 TauCl 对人诱导分化脂肪细胞在白细胞介素-1β(IL-1β)刺激下的影响。为了研究 TauCl 对脂肪因子表达的生理影响,将诱导分化的脂肪细胞用 TauCl 在浓度为 200 到 600 μM 范围内处理,处理时间为 7 天,然后用 IL-1β 进行处理或不进行处理。通过 ELISA 和实时 PCR 分别分析细胞培养上清液和总 RNA,以确定脂肪因子包括脂联素、瘦素、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)的蛋白和 mRNA 水平。通过 Western blot 检测相关信号通路中蛋白的水平。结果表明,IL-1β 刺激显著降低了脂肪细胞中脂联素和瘦素的水平,但以剂量依赖性方式增加了 IL-6 和 IL-8 的水平。TauCl 处理通过抑制 IL-1β 刺激的脂肪细胞中的 STAT-3 信号转导,显著逆转了脂肪因子表达的调节,而不依赖于丝裂原活化蛋白激酶(MAPK)信号转导。TauCl 处理更显著地调节了受 IL-1β 刺激的脂肪细胞中脂肪因子的表达,而不是未受刺激的脂肪细胞,这表明 TauCl 在炎症条件下调节脂肪因子表达中起着重要作用。总之,TauCl 和其他抑制 STAT-3 信号通路的牛磺酸衍生物可以调节脂肪因子的表达,因此可能作为肥胖相关疾病的治疗剂。

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