The thermoregulatory and energy homeostasis systems are tightly coupled to ensure the stability of both core temperature and body fat stores across a wide range of environmental temperatures. This interaction is highlighted by the adaptive metabolic response to cold exposure, as the increase of heat production needed to maintain core temperature is accompanied by a proportionate increase in energy intake to maintain body fat stress. These adaptive responses are rapid and robust and our recent findings implicate a role for agouti- related peptide (Agrp) neurons in the adaptive feeding response since Agrp neurons are activated during cold- exposure, and this activation is required for cold-induced hyperphagia, but not cold-induced thermogenic responses. The overarching goal of the proposal is to identify the neurocircuitry linking thermoregulation to control of Agrp neuronal activity and associated feeding responses. Proposed studies seek 1) to examine the temporal relationship between changes in ambient temperature, Agrp neuron activity and associated feeding responses and 2) to identify and characterize neurocircuits that link thermoregulation to cold-induced hyperphagia. To accomplish this, state-of-the-art neuroscience techniques including chemogenetics, optogenetics and fiber photometry systems approaches are utilized, in combination with immunohistochemical and advanced metabolic phenotyping. Together, this work will advance the understanding of the neurocircuitry linking thermoregulation to Agrp neurons and feeding and may identify novel strategies for the treatment of obesity by blunting the associated hyperphagic response.
Obesity is among the most pressing and costly medical challenges confronting modern society and even with currently available therapies, achieving long-term weight reduction remains a challenge. Using cold exposure as an experimental paradigm, our recent findings suggests a novel link between thermoregulatory neurocircuits and agouti-related peptide neurons that regulate food intake. This work has the potential to fundamentally advance our understanding of how the brain regulates feeding and to identify novel strategies for the treatment of obesity by blunting the associated hyperphagic response.
