DOI

10.17077/etd.x32e3ml3

Document Type

Dissertation

Date of Degree

Spring 2018

Access Restrictions

Access restricted until 07/03/2019

Degree Name

PhD (Doctor of Philosophy)

Degree In

Pharmacology

First Advisor

Kamal Rahmouni

First Committee Member

Justin L. Grobe

Second Committee Member

Stefan Strack

Third Committee Member

Yuriy M. Usachev

Fourth Committee Member

Huxing Cui

Abstract

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.

Keywords

hypertension, leptin, obesity, sympathetic nerve activity

Pages

xiii, 131 pages

Bibliography

Includes bibliographical references (pages 116-125).

Copyright

Copyright © 2018 Balyssa Bridget Bell

Available for download on Wednesday, July 03, 2019

Included in

Pharmacology Commons

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