| Summary: | Thesis (Ph.D.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. === In obesity, there is an increase in reactive oxygen species (ROS) within adipose tissue that is caused by increases in the inflammatory milieu and also over nutrition. In parallel, in obesity there is increased adipocyte lipolysis and increased lipid synthesis meaning that lipid turnover, or the combined flux of these two metabolic pathways is increased. What is unknown is how and if ROS play a causal role in these functional changes that occur in adipocytes during the
progression of obesity.
This thesis seeks to examine the relationship between ROS and lipid turnover. We argue that ROS is causal and perhaps this increase in 'futile cycling', i.e. increased lipid turnover, is an adaptation to promote lipid storage within adipocytes and reduce partitioning of lipid into other metabolic organs.
Antioxidants were employed as a tool to modulate ROS and it was found that altered ROS did in fact alter lipid turnover in adipocytes. Scavenging ROS inhibited both lipid synthesis and lipolysis, with a net effect of decreased lipid turnover. One of the targets of altered ROS in the context of lipid turnover was the lipolytic enzyme, hormone sensitive lipase (HSL). Phosphorylation of a key serine residue on HSL and also translocation of this enzyme from the cytosol to the lipid droplet upon lipolytic stimulation were both abrogated by scavenging ROS. Perhaps there are other enzymes involved in lipid turnover regulated in a similar manner.
These findings are significant not only for the implications of increased lipid turnover by ROS during obesity, but they also suggests that ROS contributes to the physiological regulation of lipid turnover and this added layer of regulation could be useful in developing new obesity therapies.
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