摘要：SummaryIn the melanocortin pathway, melanocortin-4 receptor (MC4R) functions to control energy homeostasis. MC4R is expressed in a sub-population of Sim1 neurons (Sim1/MC4R neurons) and functions in hypothalamic paraventricular nuclei (PVN) to control food intake. Mapping sites of hypothalamic injury in obesity is essential to counteract the disease. In the PVN of male and female mice with diet-induced obesity (DIO) there is neuronal loss. However, the existing subpopulation of PVN Sim1/MC4R neurons is unchanged, but has a loss of mitochondria and MC4R protein. In mice of both sexes with DIO, dietary intervention to re-establish normal weight restores abundance of MC4R protein in Sim1/MC4R neurons and neurogenesis in the PVN. However, the number of non-Sim1/MC4R neurons in the PVN continues to remain decreased. Selective survival and recovery of Sim1/MC4R neurons after DIO suggests these neurons as preferential target to restore energy homeostasis and of therapy against obesity.Graphical AbstractDisplay OmittedHighlights•MC4R localizes to post-synaptic sites along neuronal processes•In PVN of mice with DIO, MC4R neurons survive, but non-MC4R neurons are decreased•In PVN of mice with DIO, MC4R neurons have loss of mitochondria and of MC4R protein•When mice with DIO return to normal weight, abundance of MC4R protein is restoredbiological sciences; human physiology; and molecular neuroscience
