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Publication : Lateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state.

First Author  You IJ Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  6875
PubMed ID  37898655 Mgi Jnum  J:355344
Mgi Id  MGI:7546353 Doi  10.1038/s41467-023-42623-6
Citation  You IJ, et al. (2023) Lateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state. Nat Commun 14(1):6875
abstractText  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(Penk)) 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(Penk) neurons to HFD, whereas pharmacological inhibition of GR in the LH suppresses PSS-induced maladaptive behavioral responses. We have thus identified the LH(Penk) neurons as a critical component in the threat-induced neuronal adaptation that leads to emotional overconsumption.
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