Publication Date
5-30-2023
Journal
Cell Reports
DOI
10.1016/j.celrep.2023.112502
PMID
37171957
PMCID
PMC10317244
PubMedCentral® Posted Date
7-3-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Humans, Paraventricular Hypothalamic Nucleus, Melanocortins, Obesity, Body Weight, Glutamic Acid
Abstract
The melanocortin pathway is well established to be critical for body-weight regulation in both rodents and humans. Despite extensive studies focusing on this pathway, the downstream brain sites that mediate its action are not clear. Here, we found that, among the known paraventricular hypothalamic (PVH) neuron groups, those expressing melanocortin receptors 4 (PVHMc4R) preferably project to the ventral part of the lateral septum (LSv), a brain region known to be involved in emotional behaviors. Photostimulation of PVHMc4R neuron terminals in the LSv reduces feeding and causes aversion, whereas deletion of Mc4Rs or disruption of glutamate release from LSv-projecting PVH neurons causes obesity. In addition, disruption of AMPA receptor function in PVH-projected LSv neurons causes obesity. Importantly, chronic inhibition of PVH- or PVHMc4R-projected LSv neurons causes obesity associated with reduced energy expenditure. Thus, the LSv functions as an important node in mediating melanocortin action on body-weight regulation.
Graphical Abstract
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Community Health and Preventive Medicine Commons, Dietetics and Clinical Nutrition Commons, Endocrinology, Diabetes, and Metabolism Commons, Neurosciences Commons, Nutrition Commons, Pediatrics Commons