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Title: Cardiac Lipoprotein Metabolism in Health and Diabetes.
Author: Niu, Youguo
ISNI:       0000 0001 3447 6339
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2007
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Triacylglycerols (TAG)-rich lipoproteins (TGRLPs), i.e. very-low-density lipoprotein (VLDL) and chylomicrons (CM), are believed to be important substrates for heart to produce ATP and to incorporate constituents of cardiomyocyte membranes. However, cardiac utilisation of TGRLPs has not been fully understood. Therefore, the aims of the study were to investigate metabolism of TGRLPs by the isolated 'working' rat heart under physiological and diabetic conditions. Radiolabelled VLDL and CM particles were prepared by an extended liver perfusion and a thoracic duct cannulation technique respectively. Streptozotocin (STZ)-treated rats and Zucker Diabetic Fatty (ZDF) rats were used as type 1 and 2 diabetic animal models. Under physiologically moderate workload conditions, both VLDL and CM could maintain the isolated heart in good 'working' performance. Lipoprotein lipase (LPL)mediated hydrolysis was the principal mechanism for heart to take up VLDL and CM. Receptor-mediated endocytosis, although less quantitatively important regarding the uptake of TGRLPs, was a mechanism which preferentially 'channelled' TAG assimilated towards oxidation rather than esterification. CM was a preferable substrate for heart to use, mainly as an energy source. VLDL, however, may have a different role in cardiac lipoprotein metabolism. Only about half of VLDL-TAG assimilated was oxidised and the oxidation rate of VLDL-TAG was markedly lower than that ofCM-TAG. In diabetic hearts, heparin-releasable LPL activity was significantly increased. But surprisingly, no significant change in TAG uptake was found in diabetes, although a slight increased trend was shown in ZDF rats. Significantly higher TAG oxidation rates and lower glucose oxidation rates were demonstrated in diabetic hearts, supporting the shift of cardiac substrate utilisation from glucose to lipids (not only non-esterified fatty acid but also TAG) in diabetes. The proportion of VLDL-TAG oxidised in diabetes was much higher than that in control, suggesting that VLDL could act as an extracellular energy store for hearts. The total tissue lipid esterification was unchanged but an enhanced TAG accumulation was found in STZtreated hearts, although cardiac performance was maintained. The effects of diabetic lipoproteins on metabolism were also demonstrated, possibly due to changes in lipoprotein particle composition, which was found to be disturbed in diabetes. These results suggest that VLDL and CM have a different metabolic role in the heart. The importance of the utilisation of these lipids was also confirmed by the findings in diabetes. Therefore, manipulation of lipoproteins and their utilisation may be important therapeutically.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available