1155-P: Neurocircuits Controlling Adaptive Thermogenesis Rely on Skin Detection of External Temperatures through Calcitonin Gene-Related Peptide Expressing Spinal Neurons

Abstract

Heat-sensory neurons arising from the dorsal root ganglia (DRG) play a pivotal role in the detection of cutaneous temperature and transmission of external signals to the brain, ensuring the maintenance of thermoregulation. However, whether these thermoreceptor neurons contribute to adaptive thermogenesis has remained elusive. We show that genetic ablation of heat sensing Calcitonin Gene-Related Peptide α (CGRPα) neurons promotes resistance to weight gain upon high fat diet (HFD) feeding and increases energy expenditure in mice. Mechanistically, we find that loss of CGRPα-expressing sensory neurons is associated with reduced lipid deposition in adipose tissue, enhanced expression of fatty-acid oxidation genes, higher ex-vivo lipolysis in primary white adipocytes and enhanced mitochondrial respiration from iBAT. Remarkably, mice lacking CGRPα sensory neurons manifest increased tail cutaneous vasoconstriction at room temperature. This exacerbated cold perception was not associated with reduced core temperature, suggesting that heat production and heat conservation mechanisms are engaged. Specific denervation of CGRPα neurons in intrascapular BAT did not contribute to the increased metabolic rate observed upon global sensory denervation. Taken together, these findings highlight an important role for cutaneous thermoreceptors in regulating energy metabolism, by triggering counter-regulatory responses involving energy dissipation processes including lipid fuel utilization and cutaneous vasodilation. Disclosure C. Riera: None. Funding American Diabetes Association/Pathway to Stop Diabetes (1-15-INI-12 to C.R.)