Fralin Biomedical Research Institute at VTC, Roanoke, VA, USA.
FBRI Center for Neurobiology Research, Roanoke, VA, USA.
Nat Commun. 2023 Oct 28;14(1):6875. doi: 10.1038/s41467-023-42623-6.
Psychological stressors, like the nearby presence of a predator, can be strong enough to induce physiological/hormonal alterations, leading to appetite changes. However, little is known about how threats can alter feeding-related hypothalamic circuit functions. Here, we found that proenkephalin (Penk)-expressing lateral hypothalamic (LH) neurons of mice exposed to predator scent stimulus (PSS) show sensitized responses to high-fat diet (HFD) eating, whereas silencing of the same neurons normalizes PSS-induced HFD overconsumption associated with a negative emotional state. Downregulation of endogenous enkephalin peptides in the LH is crucial for inhibiting the neuronal and behavioral changes developed after PSS exposure. Furthermore, elevated corticosterone after PSS contributes to enhance the reactivity of glucocorticoid receptor (GR)-containing LH neurons to HFD, whereas pharmacological inhibition of GR in the LH suppresses PSS-induced maladaptive behavioral responses. We have thus identified the LH neurons as a critical component in the threat-induced neuronal adaptation that leads to emotional overconsumption.
心理压力源，如临近的捕食者的存在，可能强大到足以引起生理/荷尔蒙的改变，导致食欲变化。然而，对于威胁如何改变与进食相关的下丘脑回路功能，我们知之甚少。在这里，我们发现暴露于捕食者气味刺激（PSS）的小鼠的脑啡肽原（Penk）表达的外侧下丘脑（LH）神经元对高脂肪饮食（HFD）的进食表现出敏感的反应，而相同神经元的沉默则使 PSS 诱导的 HFD 过度摄入正常化，与负面情绪状态有关。LH 中内源性脑啡肽肽的下调对于抑制 PSS 暴露后出现的神经元和行为变化至关重要。此外，PSS 后皮质酮的升高有助于增强含有糖皮质激素受体（GR）的 LH 神经元对 HFD 的反应性，而 LH 中 GR 的药理学抑制则抑制了 PSS 诱导的适应性行为反应。因此，我们已经确定 LH 神经元是导致情绪过度摄入的威胁诱导神经元适应的关键组成部分。
