期刊
NEURON
卷 72, 期 4, 页码 616-629出版社
CELL PRESS
DOI: 10.1016/j.neuron.2011.08.027
关键词
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资金
- European Research Council (ERC)
- Osk. Huttunen Foundation
- NIH
- FRS-FNRS
- NARSAD
- Lundbeck Foundation
- MRC in UK
- MRC in Denmark
- MRC [MC_U137881016, G0800500] Funding Source: UKRI
- Medical Research Council [G0800500, MC_U137881016, G1000800i] Funding Source: researchfish
Hypothalamic orexin/hypocretin (orx/hcrt) neurons regulate energy balance, wakefulness, and reward; their loss produces narcolepsy and weight gain. Glucose can lower the activity of one/hcrt cells, but whether other dietary macronutrients have similar effects is unclear. We show that orx/hcrt cells are stimulated by nutritionally relevant mixtures of amino acids (AAs), both in brain slice patch-clamp experiments, and in c-Fos expression assays following central or peripheral administration of AAs to mice in vivo. Physiological mixtures of AAs electrically excited orx/hcrt cells through a dual mechanism involving inhibition of K(ATP) channels and activation of system-A amino acid transporters. Nonessential AAs were more potent in activating orx/hcrt cells than essential AAs. Moreover, the presence of physiological concentrations of AAs suppressed the glucose responses of orx/hcrt cells. These results suggest a new mechanism of hypothalamic integration of macronutrient signals and imply that orx/hcrt cells sense macronutrient balance, rather than net energy value, in extracellular fluid.
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