Date of Degree
Access restricted until 07/03/2019
PhD (Doctor of Philosophy)
First Committee Member
Justin L. Grobe
Second Committee Member
Third Committee Member
Yuriy M. Usachev
Fourth Committee Member
Secreted by adipose tissue, leptin acts as a signal of energy reserve status, and acts in the brain as a negative feedback mechanism to suppress food intake and increase energy expenditure, the net effect of which is maintenance of energy homeostasis. In addition to its role as a satiety factor, leptin has widespread autonomic effects, increasing sympathetic tone to a variety of tissues, including those involved in arterial pressure regulation. Thus, leptin has been implicated as a critical link between obesity and hypertension. However, the specific mechanisms whereby leptin elicits its diverse effects are not fully understood. This is further complicated by the many sites of leptin action within the brain, as well as its diverse intracellular effects. Here, we investigate the possibility that distinct aspects of leptin function are controlled by different neuronal populations and/or molecular signaling cascades. Specifically, we identify unique roles for leptin action on POMC and AgRP neurons in differentially mediating the regional sympathetic effects of leptin. Furthermore, we show that leptin action via mTORC1 is required for the cardiovascular sympathetic but not the metabolic effects. Together, these findings point to complex neuroanatomical and molecular differences in the mechanisms underlying leptin’s effects on different physiological processes, with important implications for future research into obesity-associated hypertension.
hypertension, leptin, obesity, sympathetic nerve activity
xiii, 131 pages
Includes bibliographical references (pages 116-125).
Copyright © 2018 Balyssa Bridget Bell
Bell, Balyssa Bridget. "Hypothalamic mechanisms underlying the cardiovascular and metabolic actions of leptin." PhD (Doctor of Philosophy) thesis, University of Iowa, 2018.
Available for download on Wednesday, July 03, 2019