Pituitary adenylate cyclase-activating polypeptide receptor expression in sympathetic ganglia innervating adipose tissue

Abstract

Obesity is a disease that occurs when energy intake exceeds energy expenditure, concomitantly increasing risk of chronic diseases, including metabolic diseases such as diabetes. Research into therapeutics to correct dysregulations in energy balance is on the rise, and one notable neuropeptide being studied is pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP has been shown to regulate thermogenesis, an energy burning process regulated by the sympathetic nervous system (SNS) in response to cold stress and overfeeding, but its role within the sympathetic nerves innervating and regulating energy metabolism in adipose tissues is not well understood. We hypothesize that PACAP is acting on PACAP receptors (PAC1, VPAC1, VPAC2) expressed in stellate ganglia innervating brown adipose tissue, the main thermogenic organ in mammals. We have established a reliable protocol for the isolation of two ganglia of the SNS (stellate and superior cervical) and provided recommendations of reference genes to use as internal controls for gene expression studies. For the first time, we confirmed PACAP receptor gene expression in the stellate ganglia, and saw sex-specific, differential gene expression based on housing temperature. We subsequently analyzed the expression of PAC1 splice variants in the stellate ganglia and our positive control tissues (adrenal gland and superior cervical ganglia), identifying at least two variants in these SNS tissues. This work adds to current literature on the study of thermogenesis and energy balance, and encourages future work characterizing G-protein coupled receptors (GPCRs) for their therapeutic application, enhancing our fundamental understanding of autonomic physiology in mammals.