Type of Document Dissertation Author Foster, Michelle Tranace Author's Email Address mfoster2@student.gsu.edu URN etd-11162005-154631 Title Central Nervous System Regulation of Fat Cell Lipid Mobilization: The Role of the Sympathetic Nervous System Degree Ph.D. Department Biology Advisory Committee
Advisor Name Title Timothy Bartness Committee Chair Elliott Albers Committee Member Ruth Harris Committee Member Sarah Pallas Committee Member Keywords
- Sympathetic Nervous System (SNS)
- Lipid Mobilization
- Sympathetic Denervation
- Bromodeoxyuridine (BrdU)
- Paraventricular Nucleus (PVN)
- Obesity
- White Adipose Tissue (WAT)
Date of Defense 2005-11-01 Availability restricted Abstract Obesity is a growing disorder in the United States, affecting over 60% of thepopulation. We previously defined sympathetic nervous system (SNS) outflow from
brain to white adipose tissue (WAT) using a viral transneuronal tract tracer. SNS
innervation of WAT is the principle initiator of lipolysis, whereas decreases in
sympathetic drive promote lipid accumulation. Which of the many origins of SNS
outflow from brain to WAT results in SNS-mediated changes in lipid mobilization
(increases in drive) or accumulation (decrease in drive) is unknown. Previous research
indicates that sympathetic denervation blocks lipid mobilization; thus, rostral sites in the
neuroaxis connected to WAT via the SNS may promote WAT lipid mobilization. The
hypothalamic paraventricular nucleus (PVN) may play a role via its descending
projections to the intermediolateral horn of the spinal cord. Therefore, the consequences
of PVN lesions (PVNx) on WAT mobilization or accumulation were tested. PVNx
resulted in increased lipid accumulation, indicated by increases in retroperitoneal
(RWAT) , epididymal (EWAT) , and inguinal WAT (IWAT) pad masses, in fed
hamsters, but PVNx did not block fasting (56 h)-induced lipid mobilization. Because
adrenal medullary catecholamines, especially epinephrine, also play a minor role in lipid
mobilization, we tested the contribution of catecholamine release on lipid mobilization
through adrenal demedullation (ADMEDx), with and without PVNx, and found fastinginduced
lipid mobilization was not blocked. There was, however, a suggestion that distal
denervation of IWAT, with and without ADMEDx, partially blocked lipid mobilization.
In addition, evidence suggests SNS also may be an important controller of fat cell
proliferation. Surgical denervation of WAT triggers increases in fat cell number (FCN),
but have not determined if this FCN increase is due to preadipocyte proliferation or
differentiation of preadipocytes into mature fat cells. We also have not demonstrated
what role sensory innervation may have in regulating white adipocyte proliferation.
Therefore, the role of WAT sympathetic or sensory innervation on adipocyte proliferation
was tested. The SNS but not sensory denervation triggered bona fide proliferation as
indicated by bromodeoxyuridine plus AD3, a specific adipocyte membrane protein, colabeling.
These and previous data suggest that the SNS plays a role in regulating
adiposity.
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