This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long term objective of this research is to gain an understanding of the neural pathways and cellular mechanisms that are involved in the metabolic regulation of energy expenditure and to determine how alterations in these mechanisms contribute to overweight and obesity and thereby increase the incidence of cardiovascular disease. This model is especially relevant since obesity is a major risk factor for cardiovascular diseases, and the functional amount of brown adipose tissue is inversely correlated with obesity. These studies utilize functional neuroanatomical and in vivo electrophysiological techniques to elucidate the organization and pharmacology of the neural pathway responsible for the glucoprivation-induced decrease in sympathetic activation of brown adipose tissue. The three specific aims test 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 glucoprivation-induced decrease in energy expenditure in brown adipose tissue. Progress thus far has indicated that neurons within the paraventricular hypothalamus provide an inhibitory input to the sympathetic pathways mediating thermogenesis in brown adipose tissue. 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 reverse the decrease in energy expenditure associated with dietary restriction and thereby combat obesity, thus alleviating a major risk factor for hypertension and cardiovascular disease.
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