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Title: Biochemical profiling of adipocyte metabolism
Author: Haynes, Kaylie
ISNI:       0000 0004 2745 3712
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2012
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Obesity is a worldwide health issue that has reached epidemic proportions, and is defined as increased white adipose tissue mass. This increase in adiposity is caused by either hypertrophy of existing mature adipocytes, or hyperplasia of pre-adipocytes, leading to increased adipocyte numbers. The current study used the murine 3T3-L1 pre-adipocyte cell line to explore in vitro the differentiation process from pre-adipocytes to mature adipocytes, termed adipogenesis. Lipidomic analyses demonstrated a shift in the predominant lipid species present; from phospholipids in the pre-adipocytes, to triglycerides in the mature adipocytes. This was expected from the morphological changes known to occur in this cell line, from fibroblastic pre-adipocytes, to spherical lipid-loaded mature adipocytes. The production of various eicosanoids was also investigated, and their concentration was greatest during the pre-adipocyte stage. This profile was also seen with arachidonic acid, a precursor in eicosanoid synthesis. These changes in lipid metabolism and eicosanoid production appeared to be linked, allowing the differentiation process and lipid accumulation to continue. The obese state is also associated with a chronic low-grade inflammation, and so the effects of TNF-α and IL-6 intervention on adipocyte metabolism were investigated. Differences in lipid mobilisation caused by these pro-inflammatory agents were suggested due to increases or decreases observed in the concentrations of various triglyceride and fatty acid species. Increases were observed in the concentration of various detected eicosanoid species from the arachidonic acid cascade, mainly prostanoid species. Effects of the anti-inflammatory agent dexamethasone were also investigated in mature 3T3-L1 adipocytes. It was associated with increases in the concentration of both triglyceride and fatty acid species, suggesting possible increase in lipogenesis and/or decrease in lipolysis. Increases in the production of various eicosanoid species from the arachidonic acid pathway were also observed. The majority of these species are pro-inflammatory; however, PGE2 is known to have both pro-and anti-inflammatory effects, and this may help to explain these findings. In conclusion, the work presented in this thesis has revealed how adipocyte metabolism changes in the naturally occurring stages of adipogenesis, as well as in response to pro- and anti-inflammatory intervention. Associations were observed between adipokine gene expression, lipid metabolism and eicosanoid production; however, further work is required to confirm these links by identifying the underlying mechanisms involved.
Supervisor: Pickavance, Lucy C.; Whitfield, Phillip; German, Alex Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available