Reichenbach Alex, Dempsey Harry, Andrews Zane B
Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, Victoria, Australia.
Florey Institute of Neuroscience & Mental Health, Parkville, Victoria, Australia.
J Neuroendocrinol. 2024 May;36(5):e13389. doi: 10.1111/jne.13389. Epub 2024 Apr 10.
Hunger increases the motivation for calorie consumption, often at the expense of low-taste appeal. However, the neural mechanisms integrating calorie-sensing with increased motivation for calorie consumption remain unknown. Agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus sense hunger, and the ingestion of caloric solutions promotes dopamine release in the absence of sweet taste perception. Therefore, we hypothesised that metabolic-sensing of hunger by AgRP neurons would be essential to promote dopamine release in the nucleus accumbens in response to caloric, but not non-caloric solutions. Moreover, we examined whether metabolic sensing in AgRP neurons affected taste preference for bitter solutions under conditions of energy need. Here we show that impaired metabolic sensing in AgRP neurons attenuated nucleus accumbens dopamine release in response to sucrose, but not saccharin, consumption. Furthermore, metabolic sensing in AgRP neurons was essential to distinguish nucleus accumbens dopamine response to sucrose consumption when compared with saccharin. Under conditions of hunger, metabolic sensing in AgRP neurons increased the preference for sucrose solutions laced with the bitter tastant, quinine, to ensure calorie consumption, whereas mice with impaired metabolic sensing in AgRP neurons maintained a strong aversion to sucrose/quinine solutions despite ongoing hunger. In conclusion, we demonstrate normal metabolic sensing in AgRP neurons drives the preference for calorie consumption, primarily when needed, by engaging dopamine release in the nucleus accumbens.
饥饿会增加对卡路里摄入的动机，通常是以牺牲低味觉吸引力为代价。然而，将卡路里感知与增加的卡路里摄入动机整合起来的神经机制仍然未知。下丘脑弓状核中的刺鼠相关肽（AgRP）神经元感知饥饿，并且在没有甜味感知的情况下，摄入热量溶液会促进多巴胺释放。因此，我们假设AgRP神经元对饥饿的代谢感知对于响应热量溶液而非无热量溶液促进伏隔核中的多巴胺释放至关重要。此外，我们研究了AgRP神经元中的代谢感知是否会在能量需求条件下影响对苦味溶液的味觉偏好。在此我们表明，AgRP神经元中受损的代谢感知会减弱伏隔核中对蔗糖而非糖精消耗的多巴胺释放。此外，与糖精相比，AgRP神经元中的代谢感知对于区分伏隔核对蔗糖消耗的多巴胺反应至关重要。在饥饿条件下，AgRP神经元中的代谢感知增加了对添加苦味剂奎宁的蔗糖溶液的偏好，以确保卡路里摄入，而AgRP神经元中代谢感知受损的小鼠尽管持续饥饿，仍对蔗糖/奎宁溶液保持强烈厌恶。总之，我们证明AgRP神经元中的正常代谢感知通过促使伏隔核中的多巴胺释放，主要在需要时驱动对卡路里摄入的偏好。
