FGF21 regulates metabolism and circadian behavior by acting on the nervous system.
FGF21 regulates metabolism and circadian behavior by acting on the nervous system.
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成纤维细胞生长因子21（FGF 21）是一种肝细胞因子，其作为全局饥饿信号来调节燃料分配和代谢，并抑制生长;然而，这些不同作用的作用部位仍不清楚。FGF 21通过异聚体细胞表面受体发出信号，该受体由三种FGF受体（FGFR 1c、2c或3c）之一与β-Klotho复合组成，β-Klotho是一种在代谢组织中富集的单程跨膜蛋白。在这里，我们表明，除了其对外周代谢的已知影响，FGF 21增加全身糖皮质激素水平，抑制身体活动，并改变昼夜节律行为，适应性饥饿反应的所有特征。这些作用通过下丘脑的视交叉上核（SCN）和后脑的迷走神经背侧复合体（DVC）中的β-Klotho表达介导。在这些区域缺乏β-Klotho基因（Klb）的小鼠对这些影响以及对代谢、胰岛素和生长的影响是难治的。这些发现证明了神经系统在介导FGF 21的多种生理和药理作用中的关键作用。
Fibroblast growth factor 21 (FGF21) is a hepatokine that acts as a global starvation signal to modulate fuel partitioning and metabolism, and repress growth; however the site of action of these diverse effects remains unclear. FGF21 signals through a heteromeric cell surface receptor composed of one of three FGF receptors (FGFR1c, 2c, or 3c) in complex with β-Klotho, a single-pass transmembrane protein that is enriched in metabolic tissues. Here we show that in addition to its known effects on peripheral metabolism, FGF21 increases systemic glucocorticoid levels, suppresses physical activity, and alters circadian behavior, all features of the adaptive starvation response. These effects are mediated through β-Klotho expression in the suprachiasmatic nucleus (SCN) of the hypothalamus and the dorsal vagal complex (DVC) of the hindbrain. Mice lacking the β-Klotho gene (Klb) in these regions are refractory to these effects, as well as those on metabolism, insulin, and growth. These findings demonstrate a crucial role for the nervous system in mediating the diverse physiologic and pharmacologic actions of FGF21.
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DOI：
10.1073/pnas.0701600104
发表时间：
2007-05-01
影响因子：
11.1
作者：
Ogawa, Yasushi;Kurosu, Hiroshi;Kuro-o, Makoto
通讯作者：
Kuro-o, Makoto
影响因子：
15.9
作者：
Scott, Michael M.;Williams, Kevin W.;Elmquist, Joel K.
通讯作者：
Elmquist, Joel K.
影响因子：
5.6
作者：
Kharitonenkov, Alexei;Dunbar, James D.;Shanafelt, Armen B.
通讯作者：
Shanafelt, Armen B.
影响因子：
--
作者：
BUIJS, RM;KALSBEEK, A;SHINN, S
通讯作者：
SHINN, S
影响因子：
82.9
作者：
通讯作者：
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