White adipose tissue (WAT) is the chief energy storage site in the body and is densely innervated by sensory and sympathetic nerves that enable bi-directional neural communication with the central nervous system. The sympathetic neurotransmitter norepinephrine is the best-studied nerve product in WAT, and is known to stimulate lipolysis, browning (development of brown adipocytes in WAT) , thermogenesis, and other metabolically favorable processes. Conversely, sensory nerves in WAT secrete neuropeptides such as calcitonin gene related peptide (CGRP) , a vasodilatory neuropeptide that also impacts lipolysis, but has been vastly understudied. Circulating CGRP levels are known to be increased in obese humans, but given the beneficial metabolic effects of CGRP this may be a case of CGRP receptor resistance, similar to the observed leptin and insulin resistance with obesity. Therefore, a more comprehensive investigation into CGRP’s roles in adipose tissue and the importance of the sensory nerve supply for WAT function and insulin sensitivity is warranted. Using intravital calcium imaging in WAT of mice, we have observed activation of tissue nerves after application of lipids such as 13-HODE, which is an agonist of sensory nerves and leads to CGRP release. Thirty minutes after 13-HODE administration to WAT there was a significant increase in CGRP levels in WAT (by tissue ELISA) , which were reduced at 120min post-treatment. This suggests local lipid levels in WAT may trigger release of this sensory neuropeptide as an interoceptive response. With obesity, in both diet-induced and genetic ob/ob mice, we see increased WAT CGRP, which fits with reports in humans and may be due to chronically elevated tissue lipids. Exercise also increases tissue CGRP levels, perhaps due to an acute need for lipid fuels in this negative energy balance state. Taken together, CGRP is a novel factor in adipose that may be relevant for changing energy balance status and likely contributes to metabolic health.
G. Mishra: None. J. Willows: None.