NEURAL CIRCUITY RESPONSIBLE FOR METABOLIC INHIBITION OF ADAPTIVE THERMOGENESIS

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The proposed studies utilize functional neuroanatomical and in vivo electrophysiological techniques to elucidate the organization and pharmacology of the neural pathways responsible for the fasting-induced decrease in sympathetic activation of brown adipose tissue. The three specific aims test clearly defined hypotheses on the functional roles of specific neurochemically-defined neurons in the ventrolateral medulla, the paraventricular nucleus of the hypothalamus, and the raphe pallidus area in the fasting-induced decrease in energy expenditure in brown adipose tissue. This model is especially relevant since new data demonstrate brown adipose tissue in adult humans and both clinical and non-human studies demonstrate that the functional amount of this tissue is inversely correlated with obesity. Understanding the neural pathways and mechanisms that inhibit sympathetic outflow to brown adipose tissue will provide a foundation for determining how alterations in these pathways contribute to overweight and obesity, and will represent an important step towards the development of therapeutic approaches to increase energy expenditure even in the face of dietary restriction and thereby combat obesity.