published_or_final_version / Medicine / Master / Master of Research in Medicine

OBJECTIVE—Absence of stearoyl-CoA desaturase-1 (SCD1) in mice reduces plasma triglycerides and provides protection from obesity and insulin resistance, which would be predicted to be associated with reduced susceptibility to atherosclerosis. The aim of this study was to determine the effect of SCD1 deficiency on atherosclerosis. Methods and RESULTS—Despite an antiatherogenic metabolic profile, SCD1 deficiency increases atherosclerosis in hyperlipidemic low density lipoprotein receptor (LDLR)-deficient mice challenged with a western diet. Lesion area at the aortic root is significantly increased in males and females in two models of SCD1 deficiency. Inflammatory changes are evident in the skin of these mice, including increased intercellular adhesion molecule (ICAM)-1 and ulcerative dermatitis. Increases in ICAM-1 and interleukin-6 are also evident in plasma of SCD1-deficient mice. HDL particles demonstrate changes associated with inflammation, including, decreased plasma apoA-II and apoA-I and paraoxonase-1 and increased plasma serum amyloid A. Lipopolysaccharide-induced inflammatory response and cholesterol efflux are not altered in SCD1-deficient macrophages. In addition, when SCD1 deficiency is limited to bone-marrow derived cells, lesion size is not altered in LDLR-deficient mice. CONCLUSIONS—These studies reinforce the crucial role of chronic inflammation in promoting atherosclerosis, even in the presence of antiatherogenic biochemical and metabolic characteristics. [The original version of this article, along with updated information and services is located on the World Wide Web at: http://atvb.ahajournals.org/cgi/content/full/29/3/341] [UBC users: please click on the UBC eLink icon at the bottom of this record]

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Thesis (Ph. D.)--University of Sydney, 2005. / Title from title screen (viewed 19 May 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Heart Research Institute, Faculty of Medicine. Degree awarded 2005; thesis submitted 2004. Includes bibliographical references. Also available in print form.

Thesis (Ph. D.)--Florida State University, 2003. / Advisor: Dr. Robert J. Moffatt, Florida State University, College of Human Sciences, Dept. of Nutrition, Food and Exercise Sciences. Title and description from dissertation home page (viewed Sept. 15, 2005). Document formatted into pages; contains xi, 147 pages. Includes bibliographical references.

Insulin resistance is associated with a number of metabolic abnormalities that increase the risk of developing coronary heart disease. Dietary fat has been linked with insulin resistance, with alterations in the quality as opposed to the quantity of dietary fat now thought be more important in instigating improvements in insulin resistance. The aim of this work was to investigate the effect of alterations in the dietary fat intakes of middle-aged men (n = 32) on the insulin sensitivity of glucose disposal and postprandial lipid metabolism and to explore the mechanistic links between these insulin responsive pathways. Three separate dietary interventions were conducted; the first involved an increase in the intake of n-3 polyunsaturated fat, the second a decrease in saturated fat and an increase in carbohydrate and the third a decrease in saturated fat and an increase in monounsaturated fat intake. Compliance was monitored by the measurement of red blood cell phospholipid fatty acid composition, postprandial lipid metabolism was measured over 9 hours following a high-fat breakfast (80 g fat), and insulin resistance was measured using the short insulin tolerance test. The results of the study showed that while insulin sensitivity was inversely correlated with red blood cell saturated fatty acid concentration at baseline, the insulin sensitivity of glucose disposal was unaffected by any of the dietary interventions conducted. In measurements of postprandial lipaemia, improvements were observed following the low-saturated fat / high-monounsaturated fat diet and the n-3 polyunsaturated enriched diet, however the low-saturated fat/ high-carbohydrate diet was associated with a worsening of postprandial lipaemia through an increase in the concentrations of triglyceride-rich-lipoproteins. Changes in fasting biochemical measurements were most evident in the low-saturated / high-monounsaturated diet, with an 11 % reduction in total cholesterol and a 15.4 % reduction in fasting triglycerides. There were no observed changes in the activity levels or the gene expression of lipoprotein lipase. There was an unexpected positive association between the degree of insulin sensitivity and the extent of postprandial lipaemia, indicating that the link between these pathways is complex and warrants further investigation. Overall this work supports the view that dietary guidelines should be directed towards a change in the composition of fat, to a lower saturated fat intake, a higher monounsaturated fat intake and a lower n-6 : n-3 ratio through an increase in the intake of long chain n-3 polyunsaturated fatty acids.

published_or_final_version / Medicine / Master / Master of Philosophy

No description available.

Three studies were conducted to determine whether the elevated plasma and HDL cholesterol levels observed in copper-deficient rats could be explained by the interaction of ¹²⁵I-HDL subfractions with liver membrane preparations in vitro. Rats from all studies were randomly divided into two dietary treatments, copper-deficient and adequate (0.7 mg and 8.0 mg Cu/kg diet, respectively). Deionized water and diet were provided ad libitum. After eight weeks, rats were exsanguinated, membranes prepared from livers, and plasma high density lipoproteins (HDL) isolated by ultracentrifugation and agarose column chromatography. Heparin-Sepharose affinity chromatography was used to isolate specific subfractions of HDL. The HDL subfractions derived from rats of each dietary treatment were iodinated and bound to either crude liver membranes or purified liver plasma membranes prepared from rats of both treatment groups. Total binding data and computer derived estimates (K(d) and B(max)) were used to compare differences between treatments. Binding data from all experiments conformed to a one-site model. In all cases, binding was saturable and EDTA and pronase insensitive. Treatment differences were observed in Study I (¹²⁵I-apo E-free HDL binding to crude liver membranes). Significantly lower total binding and B(max) were observed when lipoproteins and membranes from copper-deficient animals were used in the assay. Competition experiments from Studies II and III demonstrate that the different HDL subfractions competed effectively with one another for binding sites, indicating that apo E is not a determinant in binding of rat ¹²⁵I-HDL subfractions to purified liver plasma membranes.