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Title: In vivo and in vitro regulation of skeletal muscle lipid metabolism
Author: Gabriel, Brendan M.
ISNI:       0000 0004 5360 4932
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2014
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Cardiovascular Disease (CVD) is the leading cause of death worldwide, a disease which has atherosclerosis at the centre of its pathology and is also linked to obesity. Atherosclerosis is known to be a chronic inflammatory disease with immune system activation. This immune activation is linked to increased postprandial triglyceride (TG) concentrations, which are an independent risk factor for the development of CVD. This thesis has demonstrated that a single bout of high intensity interval exercise (HIIE) is a low energy-expenditure (EE) and relatively time-efficient method of attenuating postprandial TG after high fat meals (HFMs). The mechanism underlying this reduction in postprandial TG is likely to be lipoprotein lipase (LPL) mediated, rather than via altered hepatic metabolism. To support this assertion the current thesis demonstrated that plasma β-hydroxybutyrate concentrations were unchanged while LPL dependent TG rich lipoprotein (TRL)-TG hydrolysis (LTTH) was increased the day after HIIE was performed. The beneficial effects do not remain when HFMs are consumed on a second day after HIIE. Furthermore HIIE does not alter select markers of postprandial immune cell activation, assessed via flow cytometric measurement of leukocyte CD11b and CD36 expression. Similarly HIIE had no effect on postprandial soluble adhesion molecule expression (sICAM-1 and sVCAM-1). On the other hand, HIIE was shown to attenuate the postprandial rise in markers of oxidative stress (plasma TBARS and protein carbonyls). In a separate study, substrate metabolism was studied in vitro in C2C12 muscle cells. Recent work has, in several mouse models, shown that reduced citrate synthase (CS) activity may be important in obesity resistance and also lower plasma TG levels, via an increase in fatty acid (FA) oxidation. However, in the current thesis, when CS activity was reduced in C2C12 muscle cells via lentiviral transduction, FA oxidation was in fact reduced when cells were incubated with glucose (5mM) and palmitate (0.8mM), for both 2 and 24 hours. These findings highlight the importance and ambiguity of CS's role as an intracellular metabolic modulator in muscle. This also warrants further research into how muscle citrate metabolism may be manipulated to improve substrate metabolism in diseases such as obesity, diabetes and CVD.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Lipids