Fibroblast growth factor 21 is expressed and secreted from skeletal muscle following electrical stimulation via extracellular ATP activation of the PI3K/Akt/mTOR signaling pathway.
Fibroblast growth factor 21 is expressed and secreted from skeletal muscle following electrical stimulation via extracellular ATP activation of the PI3K/Akt/mTOR signaling pathway.
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DOI：
10.3389/fendo.2023.1059020
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发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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作者：
成纤维细胞生长因子21(FGF21)是一种参与调节脂肪、葡萄糖和能量代谢的激素。虽然它主要由肝脏释放，但近年来的研究表明，它是一种“肌肉因子”，在运动和应激条件下，通过Akt依赖的途径在骨骼肌中合成，并分泌调节自分泌和内分泌作用。到目前为止，对骨骼肌中FGF21产生的病理生理调控的分子机制还不完全清楚。我们以前已经证明，肌膜去极化通过细胞外ATP(EATP)信号控制基因的表达，其机制被定义为“激发-转录耦合”。EATP信号调节白细胞介素6的表达和分泌，并激活Akt/mTOR信号通路。本研究旨在通过eATP信号通路和PI3K/Akt通路，研究电刺激对骨骼肌FGF21产生和分泌的调节作用。我们的结果表明，电刺激增加了FGF21的mRNA和蛋白质(细胞内和分泌的)水平，这依赖于骨骼肌细胞外的ATP信号机制。利用药物抑制剂，我们证明了肌肉中FGF21的产生和分泌需要激活P2YR/PI3K/Akt/mTOR信号通路。这些结果证实了骨骼肌在生理条件下是FGF21的来源，并揭示了在该组织中调节FGF21产生的新的分子机制。我们的结果将有助于识别新的分子靶点，以了解FGF21在生理和病理条件下的调节，如运动、衰老、胰岛素抵抗和Duchenne肌营养不良，所有这些都以FGF21水平和ATP信号成分的变化为特征。这些数据强化了eATP信号是骨骼肌中肌动蛋白表达的一个相关机制。
Fibroblast growth factor 21 (FGF21) is a hormone involved in the regulation of lipid, glucose, and energy metabolism. Although it is released mainly from the liver, in recent years it has been shown that it is a “myokine”, synthesized in skeletal muscles after exercise and stress conditions through an Akt-dependent pathway and secreted for mediating autocrine and endocrine roles. To date, the molecular mechanism for the pathophysiological regulation of FGF21 production in skeletal muscle is not totally understood. We have previously demonstrated that muscle membrane depolarization controls gene expression through extracellular ATP (eATP) signaling, by a mechanism defined as “Excitation-Transcription coupling”. eATP signaling regulates the expression and secretion of interleukin 6, a well-defined myokine, and activates the Akt/mTOR signaling pathway. This work aimed to study the effect of electrical stimulation in the regulation of both production and secretion of skeletal muscle FGF21, through eATP signaling and PI3K/Akt pathway. Our results show that electrical stimulation increases both mRNA and protein (intracellular and secreted) levels of FGF21, dependent on an extracellular ATP signaling mechanism in skeletal muscle. Using pharmacological inhibitors, we demonstrated that FGF21 production and secretion from muscle requires the activation of the P2YR/PI3K/Akt/mTOR signaling pathway. These results confirm skeletal muscle as a source of FGF21 in physiological conditions and unveil a new molecular mechanism for regulating FGF21 production in this tissue. Our results will allow to identify new molecular targets to understand the regulation of FGF21 both in physiological and pathological conditions, such as exercise, aging, insulin resistance, and Duchenne muscular dystrophy, all characterized by an alteration in both FGF21 levels and ATP signaling components. These data reinforce that eATP signaling is a relevant mechanism for myokine expression in skeletal muscle.
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影响因子：
3.7
作者：
Kim KH;Kim SH;Min YK;Yang HM;Lee JB;Lee MS
通讯作者：
Lee MS
影响因子：
7.7
作者：
Hojman P;Pedersen M;Nielsen AR;Krogh-Madsen R;Yfanti C;Akerstrom T;Nielsen S;Pedersen BK
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Pedersen BK
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DOI：
10.1139/h2012-091
发表时间：
2012-12
期刊：
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme
影响因子：
--
作者：
Fletcher JA;Meers GM;Laughlin MH;Ibdah JA;Thyfault JP;Rector RS
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Rector RS
响应剧烈运动而改变了GDF15和FGF21水平：对马拉松运动员的研究。
影响因子：
4
作者：
Campderrós L;Sánchez-Infantes D;Villarroya J;Nescolarde L;Bayès-Genis A;Cereijo R;Roca E;Villarroya F
通讯作者：
Villarroya F
影响因子：
3.5
作者：
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通讯作者：
Walsh, Kenneth