Nat Neurosci—科学家发现预防肥胖的关键神经环路：IPAC的NTS神经元是关键！！

中文摘要

肥胖是一种全球性流行病，与许多危及生命的疾病有因果关系。除了一些罕见的遗传条件外，暴饮暴食和活动减少的生物学驱动因素尚不清楚。在这项研究中，研究人员发现，小鼠前连合（IPAC）后肢间质核（中央杏仁核的延伸核团）中表达神经降压素的神经元编码了对不健康的能量密集型食物的饮食偏好。光遗传激活IPACNts神经元促进肥胖行为，如享乐性进食，并调节食物偏好。相反，对IPACNts神经元的急性抑制会减少一般进食行为及享乐性进食。IPACNts神经元的慢性抑制复刻了上述效应，小鼠减少了对甜味、非热量刺激剂的偏好，此外，还增加了运动和能量消耗。因此，小鼠表现出长期的体重减轻和代谢健康的改善，肥胖的发生率也降低了。因此，单个神经元群体的活动双向调节能量稳态。他们的发现为预防和治疗肥胖提供了的新治疗策略。

英文摘要

Obesity is a global pandemic that is causally linked to many life-threatening diseases. Apart from some rare genetic conditions, the biological drivers of overeating and reduced activity are unclear. Here, we show that neurotensin-expressing neurons in the mouse interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a nucleus of the central extended amygdala, encode dietary preference for unhealthy energy-dense foods. Optogenetic activation of IPACNtsneurons promotes obesogenic behaviors, such as hedonic eating, and modulates food preference. Conversely, acute inhibition of IPACNts neurons reduces feeding and decreases hedonic eating. Chronic inactivation of IPACNtsneurons recapitulates these effects, reduces preference for sweet, non-caloric tastants and, furthermore, enhances locomotion and energy expenditure; as a result, mice display long-term weight loss and improved metabolic health and are protected from obesity. Thus, the activity of a single neuronal population bidirectionally regulates energy homeostasis. Our findings could lead to new therapeutic strategies to prevent and treat obesity.

参考文献：Neurotensin neurons in the extended amygdala control dietary choice and energy homeostasis.Nat Neurosci. 2022 Oct 20. doi: 10.1038/s41593-022-01178-3. Online ahead of print.

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