FGF21 Signals to Glutamatergic Neurons in the Ventromedial Hypothalamus to Suppress Carbohydrate Intake.
FGF21 Signals to Glutamatergic Neurons in the Ventromedial Hypothalamus to Suppress Carbohydrate Intake.
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DOI：
10.1016/j.cmet.2020.06.008
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发表时间：
2020-08-04
期刊：
影响因子：
29
通讯作者：
Potthoff MJ
中科院分区：
文献类型：
--
作者：
Jensen-Cody SO;Flippo KH;Claflin KE;Yavuz Y;Sapouckey SA;Walters GC;Usachev YM;Atasoy D;Gillum MP;Potthoff MJ
成纤维细胞生长因子21（FGF21）是由肝脏产生的调节营养和代谢稳态的内分泌激素。FGF21的产生增加是对大量营养素不平衡的反应，并向大脑发出信号以抑制糖的摄入和甜味偏好。然而，调节这些效应的中心靶点尚不清楚。在这里，我们确定了下丘脑中的FGF21靶细胞，并揭示了FGF21信号传导到丘脑能神经元是必要的，也足以介导FGF21诱导的糖抑制和甜味偏好。此外，我们发现FGF 21直接作用于下丘脑腹内侧（VMH），专门调节蔗糖摄入量，但不调节非营养性甜味偏好、体重或能量消耗。最后，我们的数据表明，FGF 21通过增加VMH中神经元的激活和兴奋性来影响神经元活性。因此，FGF21信号传导到VMH中的神经元是调节蔗糖摄入的神经回路的重要组成部分。FGF21是一种肝源性激素，向大脑发出信号以调节大量营养素摄入和能量稳态。在此，显示FGF 21给药向腹内侧下丘脑（VMH）中的谷氨酸能神经元发出信号以抑制糖摄入但不增加能量消耗，同时增强VMH葡萄糖敏感性神经元对升高的葡萄糖水平的葡萄糖响应性。
Fibroblast growth factor 21 (FGF21) is an endocrine hormone produced by the liver that regulates nutrient and metabolic homeostasis. FGF21 production is increased in response to macronutrient imbalance and signals to the brain to suppress sugar intake and sweet-taste preference. However, the central targets mediating these effects have been unclear. Here, we identify FGF21 target cells in the hypothalamus and reveal that FGF21 signaling to glutamatergic neurons is both necessary and sufficient to mediate FGF21-induced sugar suppression and sweet-taste preference. Moreover, we show that FGF21 acts directly in the ventromedial hypothalamus (VMH) to specifically regulate sucrose intake but not non-nutritive sweet-taste preference, body weight or energy expenditure. Finally, our data demonstrates that FGF21 affects neuronal activity by increasing activation and excitability of neurons in the VMH. Thus, FGF21 signaling to glutamatergic neurons in the VMH is an important component of the neurocircuitry that functions to regulate sucrose intake. FGF21 is a liver-derived hormone that signals to the brain to regulate macronutrient intake and energy homeostasis. Here, it is shown that FGF21 administration signals to glutamatergic neurons in the ventromedial hypothalamus (VMH) to suppress sugar intake but not increase energy expenditure, while enhancing glucose responsiveness of VMH glucose-sensitive neurons to elevated glucose levels.
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影响因子：
16.2
作者：
Dhillon, H;Zigman, JM;Lowelll, BB
通讯作者：
Lowelll, BB
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
25
作者：
Chan KY;Jang MJ;Yoo BB;Greenbaum A;Ravi N;Wu WL;Sánchez-Guardado L;Lois C;Mazmanian SK;Deverman BE;Gradinaru V
通讯作者：
Gradinaru V
影响因子：
8.1
作者：
Fisher FM;Kim M;Doridot L;Cunniff JC;Parker TS;Levine DM;Hellerstein MK;Hudgins LC;Maratos-Flier E;Herman MA
通讯作者：
Herman MA
影响因子：
2.5
作者：
Elmquist, JK;Coppari, R;Lowell, BB
通讯作者：
Lowell, BB