Endocrine regulation of thermogenesis: role of pituitary adenylate cylase-activating polypeptide (PACAP)

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Energy homeostasis is achieved by balancing the amount of energy consumed through food intake and expended by metabolic pathways induced by processes such as resting metabolic rate, physical activity and thermoregulation. In the past 20 years, knowledge of neuronal pathways regulating energy balance has developed substantially driven by a desire to understand consequences of dysregulated energy balance. My program of research aims to enhance our understanding of how and which hormones play a role in regulating energy balance. Specifically we are examining the role of the neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP) in thermoregulation. PACAP is expressed in regions of the brain that control appetite and energy expenditure, including the hypothalamus. There is evidence to suggest that PACAP produced in the hypothalamus can induce thermogenesis by activating neuronal activity in brown fat, a specialized type of fat that, when activated, produces heat. Normally mice and other mammals respond to cold exposure by activating heat-producing pathways in brown fat via the sympathetic nervous system. Using a mouse model that is deficient in PACAP, we have shown that this normal adaptation to cold does not occur if PACAP is absent, indicating PACAP is critical for the regulation of adaptive thermogenesis in brown fat. We hypothesize that PACAP-expressing neurons in the hypothalamus regulate sympathetic nerves that activate thermogenesis in brown fat. Using techniques in molecular biology, physiology and histology we aim to characterize the expression of PACAP and the PACAP receptor in these neurons and understand the functional significance of centrally expressed PACAP in regulating adaptive thermogenesis. Results from this work will provide a mechanistic understanding of how PACAP regulates thermogenesis, thus enhancing our knowledge of how hormones regulate energy balance.