1533-P: Leptin-Sensitive Sensory Nerves Mediate Cross Talk between Interscapular Brown Adipose Tissue and Proopiomelanocortin Neurons

Adipose tissues communicate with the central nervous system (CNS) through secreted adiponectins, including leptin. Recent studies have shown that, in addition to its role as an endocrine hormone, leptin also communicates with the brain through leptin-sensitive spinal sensory nerves (SS) located in the L1-L3 dorsal root ganglia (DRG) that innervate white adipose tissues. Interestingly, we observed a high expression of the leptin receptor (LEPR) in the T1-T3 DRGs, which are primarily associated with interscapular brown adipose tissue (iBAT). These findings suggest that iBAT leptin may exert metabolic functions as a paracrine sensory signal. Supporting this idea, injecting a low dose of leptin into iBAT activated LEPR signaling in the T1-T3 DRG without affecting circulating levels of leptin. Additionally, it selectively stimulated LEPR-positive T1-T3 DRG neurons. These findings indicate that LEPR not only exists in iBAT-associated DRG, but also responds to leptin and mediates neuronal activation. Interestingly, infusion of leptin into the iBAT also stimulates proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus (POMC/ARH). This suggests a potential crosstalk mediated by LEPR-positive SS between iBAT and POMC/ARH. The presence of this crosstalk is further supported by the anatomical connection between POMC/ARH neurons and iBAT-associated sensory nerves, as demonstrated by transsynaptic dual tracing. Importantly, the stimulatory effects of iBAT leptin infusion on ARH neurons are abolished when iBAT-associated sensory nerves are chemically ablated or when POMC/ARH neurons are genetically ablated. Taken together, our results indicate that iBAT has a structural and functional basis for paracrine leptin signaling via SS, which interacts with POMCARH neurons to regulate energy homeostasis. Keywords: Leptin; POMC; DRG; Spinal sensory nerve; Interscapular brown adipose tissue