Arginine reverses growth hormone resistance through the inhibition of toll-like receptor 4-mediated inflammatory pathway
Arginine reverses growth hormone resistance through the inhibition of toll-like receptor 4-mediated inflammatory pathway
复制标题
精氨酸通过抑制 Toll 样受体 4 介导的炎症途径逆转生长激素抵抗
DOI：
10.1016/j.metabol.2017.10.006
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
束刚
中科院分区：
文献类型：
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作者：
徐敬仁;朱灿俊;张梦媛;童青春;万小娟;廖正睿;蔡兴才;徐亚琼;袁业现;王丽娜;朱晓彤;王松波;高萍;习欠云;徐勇;江青艳;束刚
Objective. Growth hormone stimulates growth by increasing insulin-like growth factor 1 expression and secretion.In the presence of insufficient nutrients, GH increases, whereasIGF-1 expression becomes severely suppressed, leading to GH resistance. This study aimed to explore the effect of arginine.(Arg) on GH resistance during malnutrition and to describe its underlying mechanism.Methods. C57BL/6 J mice were injected intraperitoneally with Arg for 1 h or subjected to caloric restriction with Arg supplement in drinking water for 18 days. HepG2 cells were exposed to different Arg concentrations for 24 h. Signaling pathway agonists/inhibitors,siRNA, and overexpression plasmids were used to investigate the underlying molecular mechanism. Liver-specific toll-like receptor (TLR4) knockout mice were utilized to clarify the role of TLR4 in Arg-induced IGF-I expression and secretion..Results. Arg inhibited the TLR4 downstream pathway by binding to TLR4 and consequently activated Janus kinase 2/signal transducer and activator of transcription 5 signaling pathway. As a result, IGF-1 transcription and secretion increased. Arg activity was absent in liver-specific TLR4 knockout mice and was greatly suppressed in liver with overexpressed TLR4, suggesting that hepatic TLR4 was required and sufficient to induce GH resistance. By contrast, the mammalian target of rapamycin pathway was unnecessary for Arg activity. Arg not only significantly increased IGF-1 expression and secretion under acute.fasting and chronic CR conditions but also attenuated body weight loss.
