Paraventricular hypothalamic RUVBL2 neurons suppress appetite by enhancing excitatory synaptic transmission in distinct neurocircuits [RNA-seq]
Synaptic plasticity has been shown to participate in control of energy homeostasis.The paraventricular hypothalamus (PVH) is crucial for satiety control, though the underlying synaptic mechanisms remain unclear. Here, we show that RUVBL2 in the PVH is significantly reduced during energy deficit, and knockout (KO) of PVH RUVBL2 leads to hyperphagic obesity. We further show that KO of PVH RUVBL2 impairs the excitatory synaptic transmission by reducing presynaptic boutons and altering synaptic vesicle distribution.  Chromatin immunoprecipitation-sequencing (ChlP-seq) data show that RUVBL2 binds to the promoters of numerous genes related to synaptic plasticity, in particular synaptic vesicle and neuron axonogenesis. Meanwhile, RNA-seq data show significant changes in the expression of some genes in these two pathways. Together, this study demonstrates an essential role for PVH RUVBL2 in food intake control, and suggests that modulating synaptic plasticity could be an effective way to curb appetite and obesity. Overall design: To investigate RUVBL2 in the regultion of synaptic plasticity, we used AAV-Cre to knock out RUVBL2 in the PVH of Ruvbl2fl/fl mice. We then performed gene expression profiling using data obtained from RNA-seq of mouse PVH.