Metabolic sensing in AgRP regulates sucrose preference and dopamine release in the nucleus accumbens

IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Alex Reichenbach, Harry Dempsey, Zane B. Andrews
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Abstract

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.

Abstract Image

Abstract Image

AgRP中的代谢感应调节蔗糖偏好和伏隔核中多巴胺的释放
饥饿会增加热量消耗的动力,而这往往是以牺牲低味吸引力为代价的。然而,卡路里感应与卡路里消费动机增加之间的神经机制仍然未知。下丘脑弓状核中的阿古提相关肽(AgRP)神经元能感知饥饿,在没有甜味感知的情况下,摄入热量溶液会促进多巴胺的释放。因此,我们假设,AgRP神经元对饥饿的新陈代谢感应对于促进下丘脑伏隔核中多巴胺的释放是必不可少的,这是对热量溶液的反应,而不是对非热量溶液的反应。此外,我们还研究了在需要能量的条件下,AgRP 神经元的代谢感应是否会影响对苦味溶液的味觉偏好。我们在这里发现,AgRP 神经元的代谢感应受损会减少伏隔核多巴胺在摄入蔗糖(而非糖精)时的释放。此外,与糖精相比,AgRP神经元中的代谢感应对于区分蔗糖与糖精对多巴胺的反应至关重要。在饥饿条件下,AgRP神经元的代谢感应增加了对掺有苦味剂奎宁的蔗糖溶液的偏好,以确保卡路里的消耗,而AgRP神经元代谢感应受损的小鼠尽管持续饥饿,但仍对蔗糖/奎宁溶液保持强烈的厌恶。总之,我们证明了AgRP神经元正常的新陈代谢感应主要是在需要的时候,通过吸引伏隔核的多巴胺释放来驱动对卡路里消耗的偏好。
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来源期刊
Journal of Neuroendocrinology
Journal of Neuroendocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
6.20%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field. In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.
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