Regulation of substrate utilization and adiposity by Agrp neurons
Regulation of substrate utilization and adiposity by Agrp neurons
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DOI：
10.1038/s41467-018-08239-x
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发表时间：
2019-01-18
影响因子：
16.6
通讯作者：
Dietrich, Marcelo O.
中科院分区：
文献类型：
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作者：
Cavalcanti-de-Albuquerque, Joao Paulo;Bober, Jeremy;Dietrich, Marcelo O.
生物体在任何给定时间所利用的营养物质类型-底物利用-是能量代谢的关键组成部分。在哺乳动物中参与调节底物利用的神经元机制在很大程度上是未知的。在这里，我们发现下丘脑Agrp神经元的激活迅速改变了全身底物的利用率，增加了碳水化合物的利用率，同时降低了脂肪的利用率。这些代谢变化甚至发生在没有热量摄入的情况下，并与脂肪生成增加相结合。因此，抑制脂肪酸脱氢酶-一种介导脂肪生成的关键酶-减弱了Agrp神经元激活对底物利用的影响。在正能量平衡期间的成对喂养条件下，Agrp神经元的激活改善了代谢效率，并增加了体重增加和肥胖。相反，Agrp神经元的消融损害了脂肪量的积累。这些结果表明，Agrp神经元调节底物利用，在正能量平衡期间促进脂肪生成和脂肪量积累。
The type of nutrient utilized by the organism at any given time-substrate utilization-is a critical component of energy metabolism. The neuronal mechanisms involved in the regulation of substrate utilization in mammals are largely unknown. Here, we found that activation of hypothalamic Agrp neurons rapidly altered whole-body substrate utilization, increasing carbohydrate utilization, while decreasing fat utilization. These metabolic changes occurred even in the absence of caloric ingestion and were coupled to increased lipogenesis. Accordingly, inhibition of fatty acid synthase-a key enzyme that mediates lipogenesis-blunted the effects of Agrp neuron activation on substrate utilization. In pair-fed conditions during positive energy balance, activation of Agrp neurons improved metabolic efficiency, and increased weight gain and adiposity. Conversely, ablation of Agrp neurons impaired fat mass accumulation. These results suggest Agrp neurons regulate substrate utilization, contributing to lipogenesis and fat mass accumulation during positive energy balance.