Accumulation of excess white adipose tissue in obesity has detrimental consequences for metabolic health. Activation of thermogenic adipocytes confers beneficial effects on metabolic health and is considered a potential therapeutic target for human obesity. Hormones modulating adaptive thermogenesis include melanocortins and pituitary adenylate cyclase-activating polypeptide (PACAP). In PACAP -/- mice, metabolism and thermogenic capacity in response to cold is impaired. I hypothesized PACAP acts in the ventromedial nucleus of the hypothalamus, upstream of the melanocortin system, to regulate sympathetic stimulation of thermogenesis. To assess this, PACAP +/+ and PACAP -/- mice were cold acclimated to 4°C and given daily injections of a melanocortin receptor agonist, Melanotan II (MTII), for 24 days. The effect of MTII on thermogenesis was examined by physiological, molecular, and histological analyses. Results show MTII partially rescued the impaired thermogenic capacity in PACAP -/- mice as compared to PACAP +/+ mice, providing evidence to support our hypothesis.
