The paraventricular nucleus of the hypothalamus (PVH) regulates many physiologic functions through a variety of neuronal pathways and mechanisms. Specifically, the need to understand the central regulation of energy balance has recently intensified as a result of the staggering increases in obesity and type II diabetes rates throughout the United States in the past two decades. The PVH is an essential regulator of feeding, yet the role of specific PVH neuronal populations in the regulation of energy balance is largely unknown. Identifying and characterizing the PVH oxytocin population not only in the regulation of energy homeostasis, but also behavior, autonomic, and neuroendocrine function is essential for the development of effective therapeutic treatments and strategies to combat obesity, type II diabetes, cardiovascular disease and behavioral disorders including autism. The PVH is a heterogenous cluster of cells that express a variety of neuropeptides. Significant evidence suggests the PVH oxytocin neuronal population as a critical regulator of energy balance. Specifically, PVH oxytocin neurons are hypothesized to be an intermediate step between peripheral adiposity signals such as leptin and the termination of feeding mediated by the hindbrain. Although oxytocin has been implicated in the control of energy balance, the specific neuronal mechanisms involved in this regulation are not well understood. The goal of this research proposal is to understand the functional connectivity of PVH oxytocin neurons, specifically concerning their role in energy balance regulation. We will stereotaxically inject a variety of cell-specific genetic tools in mice to identify PVH oxytocin circuitry and characterize the physiologic function of PVH oxytocin neurons in feeding and energy expenditure. Therefore, the proposed research will characterize the mechanisms of PVH oxytocin neuronal action throughout the central nervous system. In addition, these studies will test the potential role and necessity of PVH oxytocin neuronal activity in energy balance regulation. The completion of this study will provide insight into the functional connectivity of oxytocin neurons and the mechanisms of PVH oxytocin neuronal control of energy balance.
The dysregulation of pathways of the paraventricular nucleus of the hypothalamus results in the pathogenesis of diseases including obesity, type II diabetes, cardiovascular disease and autism. By elucidating the mechanisms of oxytocin neuronal function particularly in energy balance, we will characterize a potential neuronal population involved in obesity development and therefore identify a potential anti-obesity therapeutic target.
|Sutton, Amy K; Pei, Hongjuan; Burnett, Korri H et al. (2014) Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus. J Neurosci 34:15306-18|