Linifanib exerts dual anti-obesity effect by regulating adipocyte browning and formation
Linifanib exerts dual anti-obesity effect by regulating adipocyte browning and formation
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Linifanib 通过调节脂肪细胞褐变和形成发挥双重抗肥胖作用。
DOI：
10.1016/j.lfs.2019.01.047
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Nie Tao
中科院分区：
文献类型：
--
作者：
Zhao Shiting;Chu Yi;Zhang Yuwei;Zhou Yulai;Jiang Zhiwu;Wang Zhengqi;Mao Liufeng;Li Kuai;Sun Wei;Li Peng;Jia Shiqi;Wang Cunchuan;Xu Aimin;Loomes Kerry;Tang Shibing;Wu Donghai;Hui Xiaoyan;Nie Tao
肥胖是由能量失衡引起的，并伴有脂肪细胞肥大和增生。因此，增加脂肪细胞能量消耗和抑制脂肪形成都是对抗肥胖的可行方法。以UCP 1 - 2A荧光素酶报告基因动物模型为筛选平台，在体外和体内实验中，发现化合物Linifanib可有效诱导UCP 1在原代腹股沟脂肪细胞中的表达。信号通路分析表明，Linifanib通过减弱STAT 3磷酸化促进脂肪细胞布朗宁。Linifanib对脂肪细胞布朗宁的作用被激活STAT 3信号级联的化合物SD 19阻断。Linifanib还通过阻断有丝分裂克隆扩增来抑制脂肪细胞分化，这可以被STAT 3激活剂拯救。总之，我们的研究结果表明，Linifanib可能作为一种潜在的药物用于治疗肥胖。
Obesity is caused by energy imbalance and accompanied by adipocyte hypertrophy and hyperplasia. Therefore, both enhancement of adipocyte energy expenditure and inhibition of adipogenesis are viable ways to combat obesity. Using theUcp1-2A-luciferase reporter animal model previously reported by us as a screening platform, a chemical compound Linifanib was identified as a potent inducer of UCP1 expression in primary inguinal adipocytesin vitroandin vivo. Signal pathway analyses showed that Linifanib promoted adipocyte browning by attenuating STAT3 phosphorylation. The effects of Linifanib on adipocyte browning were blocked by the compound, SD19, which activates the STAT3 signaling cascade. Linifanib also inhibited adipocyte differentiation, by blocking mitotic clonal expansion, which could be rescued by STAT3 activator. Taken together, our results indicate that Linifanib might serve as a potential drug for the treatment of obesity.