Lateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state
| dc.contributor.author | You, In-Jee | en |
| dc.contributor.author | Bae, Yeeun | en |
| dc.contributor.author | Beck, Alec R. | en |
| dc.contributor.author | Shin, Sora | en |
| dc.date.accessioned | 2023-11-30T14:04:43Z | en |
| dc.date.available | 2023-11-30T14:04:43Z | en |
| dc.date.issued | 2023-10-28 | en |
| dc.description.abstract | 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 (LHPenk) 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 LHPenk neurons to HFD, whereas pharmacological inhibition of GR in the LH suppresses PSS-induced maladaptive behavioral responses. We have thus identified the LHPenk neurons as a critical component in the threat-induced neuronal adaptation that leads to emotional overconsumption. | en |
| dc.description.sponsorship | This study was supported by grants from National Institutes of Health (NIH) R01DK132566 to S.S. Fralin Biomedical Research Institute Seale Innovation fund awards to S.S. and the integrated Translational Health Research Institute of Virginia (iTHRIV) funding to S.S. in part by the National Center for Advancing Translational Sciences, NIH, through grant KL2TR003016/UL1TR003015. | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.doi | https://doi.org/10.1038/s41467-023-42623-6 | en |
| dc.identifier.uri | https://hdl.handle.net/10919/116711 | en |
| dc.language.iso | en | en |
| dc.publisher | Nature Research | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.title | Lateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |