The role of pituitary adenylate cyclase-activating polypeptide in sympathetic regulation of brown adipose tissue function

Obesity is a multi-factorial, chronic metabolic disease that forms due to the imbalance of energy metabolism. Scientists are actively working to identify potential therapeutic targets to combat obesity. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been recognized as a neuropeptide involved in regulating adaptive thermogenesis, a physiological mechanism of energy expenditure. The role of PACAP in catecholamine secretion is wellstudied at the sympatho-adrenomedullary axis; however, the function of PACAP in the pripheral sympathetic nervous system (SNS) is not characterized. We developed an ex vivo model aiming to study PACAP‟s role in the peripheral ganglia in regulating catecholamine secretion and downstream adrenergic signaling. To validate the model, we used two nicotinic acetylcholine receptor (nAChR) agonists (dimethylphenylpiperazinium (DMPP), nicotine) to stimulate postganglionic nerves of the stellate ganglia and assessed molecular markers (cyclic adenosine monophosphate (cAMP) and phospho-hormone-sensitive lipase (p-HSL) (Ser563)) of norepinephrine-stimulated adrenergic signaling in interscapular brown adipose tissue (iBAT). Delivering nAChR agonists to the stellate ganglia did not increase the production of cAMP and p-HSL (Ser563) in iBAT, demonstrating that, as currently implemented, our model is not suitable to study PACAP‟s function in the peripheral ganglia. Although the model was deemed to be unsuccessful, outcomes of this study have helped us understand the challenges of working with a sympathetic ganglion, and the optimization of protocols to measure molecular markers of adrenergic stimulation established in this study will be useful for future studies examining sympathetic nerve activity in peripheral organs.