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Title: The effects of diet and gastrointestinal hormones on lipoprotein lipase activity and gene expression
Author: Chapman, Clare
ISNI:       0000 0001 3528 8946
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1996
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The rate of postprandial fat clearance from the circulation has long been implicated as a risk factor for coronary heart disease. The extent and duration of postprandial lipaemia is regulated by LPL. LPL activity is known to be affected by the dietary fatty acid content of the habitual diet. We therefore hypothesised that feeding frequency and habitual fatty acid intake would modulate LPL activity and may affect gene expression. The level of this control was investigated initially by studying the effects of gastrointestinal hormones on rat adipose tissue LPL activity. In explants of rat adipose tissue GIP (4nM), insulin (2nM) and GLP-1 (7-36) amide (4nM) were found to stimulate heparin-releasable LPL activity. Similar concentrations of GLP-1 (7-37), GLP-1 (1-36) amide or GLP-1 (1-37) produced no effect on LPL activity. Melatonin significantly increased LPL activity at a concentration of 8nM but not at 4nM. Since gastrointestinal hormones are stimulated by the dietary intake of fat and carbohydrates, the action of insulin, GIP and GLP-1 (7-36) amide on LPL activity provides a direct link between dietary intake and postprandial nutrient metabolism. Under normal physiological conditions meal frequency has been shown to affect fasting triacylglycerol, cholesterol and GIP levels (Wolever, 1990; McGrath & Gibney, 1994). Few effects on postprandial lipid metabolism were found as a result of altering meal frequency in young healthy women which suggested that diet composition was a more important determinant of postprandial lipaemia. Alterations in maternal nutrition during pregnancy may irreversibly affect aspects of physiological and biochemical functions in the offspring (Barker et al. 1993). A rat study was performed to investigate the effects of a high n-3 PUFA intake in the maternal diet on postprandial hormone and nutrient metabolism in the offspring. Most of the changes exhibited during this study were due to developmental changes with age. Increasing the mixed oil intake of pregnant rats increased LPL mRNA levels in the offspring - an effect which persisted into later life. This study therefore confirms that maternal and early diet do affect LPL gene expression and therefore possibly risk of atherogenesis in adult life. There is strong evidence that dietary fatty acid composition influences LPL activity. However, there is little understanding of whether the level of control is hormone or substrate driven. A technique to measure human LPL mRNA was developed to enable the assessment of the level of control of LPL in adipose tissue. The level of LPL expression in humans was found to be 6% of that in rats.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry