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首页> 外文期刊>Cell Reports >mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes
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mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes

机译：mTORC1是脂肪细胞FGF21信号网络中的主要调控节点

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FGF21 improves the metabolic profile of obese animals through its actions on adipocytes. To elucidate the signaling network responsible for mediating these effects, we quantified dynamic changes in the adipocyte phosphoproteome following acute exposure to FGF21. FGF21 regulated a network of 821 phosphosites on 542 proteins. A major FGF21-regulated signaling node was mTORC1/S6K. In contrast to insulin, FGF21 activated mTORC1 via MAPK rather than through the canonical PI3K/AKT pathway. Activation of mTORC1/S6K by FGF21 was surprising because this is thought to contribute to deleterious metabolic effects such as obesity and insulin resistance. Rather, mTORC1 mediated many of the beneficial actions of FGF21 in vitro, including UCP1 and FGF21 induction, increased adiponectin secretion, and enhanced glucose uptake without any adverse effects on insulin action. This study provides a global view of FGF21 signaling and suggests that mTORC1 may act to facilitate FGF21-mediated health benefits in vivo.
机译：FGF21通过其对脂肪细胞的作用改善了肥胖动物的代谢状况。为了阐明负责介导这些作用的信号网络，我们量化了急性暴露于FGF21后脂肪细胞磷酸化蛋白质组的动态变化。 FGF21调节542个蛋白上的821个磷酸位点的网络。 FGF21调控的主要信号转导节点是mTORC1 / S6K。与胰岛素相反，FGF21通过MAPK而不是通过经典的PI3K / AKT途径激活mTORC1。令人惊奇的是，FGF21激活了mTORC1 / S6K，因为这被认为有助于有害的代谢作用，例如肥胖和胰岛素抵抗。相反，mTORC1在体外介导了FGF21的许多有益作用，包括UCP1和FGF21诱导，脂联素分泌增加和葡萄糖摄取增加，而对胰岛素作用没有任何不利影响。这项研究提供了FGF21信号传导的全局视图，并暗示mTORC1可能在体内促进FGF21介导的健康益处。

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