Role of pituitary adenylate cyclase-activating polypeptide in energy expenditure including the thermogenic response

Obesity results when energy intake chronically exceeds energy expenditure, driving accumulation and malfunctioning of white adipose tissue and increasing risk for comorbidity. Brown adipose tissue (BAT) burns energy via adaptive thermogenesis, a process gaining therapeutic interest to restore energy balance in obesity. PACAP regulates energy expenditure including thermogenesis in BAT, but the neuronal circuits involved are not well known. Thus, we aim to develop a tool to safely restore PACAP in the hypothalamic ventromedial nucleus (VMN) of PACAP-null mice to assess the VMN’s contribution. We also investigated whether PACAP directly regulates BAT function by binding at adipocytes. We discovered PACAP receptor expression in BAT and genetic regulation of receptor expression with cold acclimation. Acute in vitro studies did not show PACAP-stimulated thermogenesis in BAT. Studying adaptive thermogenesis and its hypothalamic regulation will contribute to the field of energy metabolism, and the pathophysiology of obesity and type 2 diabetes.