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Title: The influence of dietary factors on human plasma triacyglycerol-rich lipoproteins
Author: Hawdon, Anne J.
ISNI:       0000 0001 3546 5738
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2001
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Coronary heart disease is one of the major causes of death and morbidity in the U.K population and many other industrialised countries. An atherogenic lipoprotein phenotype may represent the most common source of lipid-mediated coronary heart disease risk in the 'free-living' population, and the structural heterogeneity of triacylglycerol-rich lipoproteins (TGRL) may be of relevance to this. However, few methods have been able to accurately distinguish between very low density lipoproteins (VLDL) and chylomicrons (CM), and to differentiate between the methodologically defined 'light'-VLDL and 'dense'-VLDL (Bjorkegren et al., 1997). The inability to quickly resolve structural heterogeneity in the TGRL by conventional salt density gradients, led to the development of a rapid method for the separation of TGRL from an original iodixanol self-forming gradient method Graham (unpublished) which produced TGRL-TAG profiles. After centrifugation the gradient was fractionated on the basis of the TAG profile into three pools; 'light'-TGRL, 'light'-VLDL and 'dense'-VLDL. These pools could then be further characterised by the analysis for apo B-48. The iodixanol gradient was validated by comparison with TGRL separated by cumulative flotation i.e. light-VLDL (VLDL1) and dense-VLDL (VLDL2) which were isolated by cumulative flotation and then co-isolated on the iodixanol gradient. The iodixanol gradient was used to investigate the role of the TGRL subclasses in the generation of postprandial lipaemia produced by 1) an acute effect of ethanol; 2) carbohydrate loading 3) attenuation of postprandial lipaemia by unsaturated fatty acids; monounsaturated fatty acid (MUFA) and n-3 polyunsaturated fatty acids (PUFA). The acute effects of ethanol (0.6 g/kg), after a 51 g fat meal produced a significant increase in postprandial plasma TAG compared to control in the late phases of lipaemia at 360 min (33%, p < 0.05), in TRL-apo B-48 (8 %, p48 %, p < 0.05). This effect was associated with a decreases in lipoprotein (LPL) and hepatic lipase-(HL) activity of 12 % and 25 % respectively. Acute CHO supplementation (30 % of total energy as sucrose for 4 days) produced a significant increase (36 % p97 %, p < 0.001), 'light'-VLDL (58 % p < 0.05), 'dense'-VLDL -TAG (26 %, p < 0.05) and reduced HDL-C (12 %,p < 0.05). Conversely studies with dietary unsaturated fatty acids produced the opposite effects. A MUFA enriched diet (18 % of energy intake) produced a significant reduction (21 %, p < 0.05) in postprandial lipaemia in response to a 82.7 g test meal; whereas long chain n-3 PUFA supplementation (3.01 g of EPA and DHA/d) produced a significant reduction (28 %, p < 0.001) in fasting plasma TAG. Both responses were accompanied by a reduction in 'dense' and 'light' TGRL and the MUFA diet also caused an increase in the activity of LPL. Overall, the study results shown that dietary constituents which either raise or lower TAG do so by exerting differential effects in plasma TGRL. Of the constituents that raise plasma TAG (ethanol/CHO), ethanol affects the larger TGRL 'light'-TGRL and 'light'-VLDL, whilst CHO appears to have an affect on all TGRL. Of the constituents which lower plasma TAG, MUFA affected the larger TGRL in the CM range, whilst n-3 PUFA appears to affect both the larger TGRL in the CM range and smaller TGRL 'dense'- VLDL. Although differences in study design make it difficult to directly compare these dietary interventions, these findings provide further insight into the mechanisms by which diet influences lipid mediated cardiovascular risk.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available