RNA-sequencing Reveals Altered Gene Expression in the Ventromedial Hypothalamus Following Predator Odor Exposure.

Background: Physical activity is the second largest contributor to our total daily energy expenditure (EE). Uncovering ways to increase EE during activity could yield new approaches to treat obesity. The ventromedial hypothalamus (VMH) regulates body weight by modulating muscle metabolism and sympathetic nervous system (SNS) activity. The VMH also mediates behavioral responses to predator threat. This thermogenic response is associated with weight loss and increased EE even when controlling for physical activity. While the VMH is a potential mediator of metabolic responses to predator threat, the mechanisms are unknown. Methods and Results: Exposing rats to predator odor (PO) causes a rapid increase in skeletal muscle thermogenesis that peaks between 20-30 min and dissipates to baseline by 4 hr. To probe potential targets of PO-induced metabolic responses in the VMH, we first performed qPCR for genes known to be involved in brain regulation of muscle metabolism using VMH samples from rats exposed to PO or control odor for either 30 min or 4 hr. Next, to uncover novel, relevant genes, we performed RNA-sequencing on VMH samples of rats exposed to either PO or control odor for 20 min. qPCR results show that after 4 hr of PO exposure, Discussion: Taken together, these findings suggest that acute PO exposure induces both rapid and delayed changes in VMH gene expression that likely have downstream metabolic consequences.