Includes bibliographical references (leaves 237-257). / xx, 257 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the mechanisms underlying the antiarrhythmic effects of omega-3 polyunsaturated fatty acids using adult rat ventricular cardiac myocytes. / Thesis (Ph.D.)--Adelaide University, Dept. of Physiology, 2001

[Truncated abstract] Increased incidence of hypertension, insulin resistance, obesity and dyslipidemia, collectively referred to as the metabolic syndrome, has been linked to low birth weight, an indicator of a poor fetal environment. This association reflects developmental programming, a process by which organ systems are affected during early development such that disease states are more likely to emerge in adult life. Fetal glucocorticoid overexposure is thought to be a key factor that mediates developmental programming. Accordingly, maternal treatment with the synthetic glucocorticoid dexamethasone retards fetal growth and leads to delayed puberty, hypertension, hyperinsulinemia, and hyperleptinemia, either with or without increased adiposity, in adult offspring. Importantly, the postnatal environment can either amplify or attenuate the long-term outcome of developmental programming. The focus of this thesis was whether adverse developmental programming outcomes can be attenuated by the postnatal environment and thus provide therapeutic potential. Specifically, the effects of a postnatal diet rich in omega-3 fatty acids on glucocorticoid-induced developmental programming outcomes was investigated. ... The adipocyte phenotype was examined in Study 6, with hyperleptinaemia evident in offspring at 6 and 12 months of age in dexamethasone-exposed animals on a standard omega-3 diet, but this effect was prevented by a high omega-3 diet. The pattern of plasma leptin was paralleled by changes in leptin mRNA in retroperitoneal fat. Similarly, plasma levels of the inflammatory markers IL-6 and IL-1β were upregulated by prenatal glucocorticoid exposure and these were attenuated by postnatal dietary omega-3 fatty acids. Overall, omega-3 ingestion reduced adiposity, as indicated by measures of body composition. In conclusion, the studies presented in this thesis demonstrate for the first time that many of the detrimental effects of excess glucocorticoid exposure in utero on the adult phenotype can be attenuated by a postnatal diet rich in omega-3 fatty acids. This beneficial effect of omega-3 fatty acids was associated with a reversal of some (e.g. adiposal leptin) but not all (e.g. renal GR) 'programmed' changes in gene expression. These findings raise the possibility that dietary supplementation with omega-3 fatty acids may provide a viable therapeutic option for preventing and/or reducing adverse programming outcomes in humans.

University of Macau / Institute of Chinese Medical Sciences

Errata slip inserted / Bibliography: leaves 178-199 / xxi, 199, [55] leaves, [3] leaves of plates : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Clinical and Experimental Pharmacology, and Rheumatology Unit, Royal Adelaide Hospital, 1994

[Truncated abstract] The role of fish consumption and omega-3 polyunsaturated fatty acids (PUFAs) in the prevention of disease has been the subject of much investigation in recent years. A clue that these factors might be of importance was the observation that populations consuming high levels of marine omega-3 PUFAs had lower rates of morbidity and mortality from cardiovascular disease. From there, research in this area has expanded to include a range of chronic diseases and their prevention. An area of particular interest is the role of fish consumption in the prevention of various cancers. In Australia, one in three men and one in four women are expected to be diagnosed with cancer by the age of 75. Identifying preventive factors that can be translated into constructive health promotional messages is of great importance in addressing this group of diseases that has such a large impact on the health and wellbeing of the population. ... Results and conclusions Analysis of the data from the population-based case-control study suggests a protective effect of preserved fish consumption, possibly due to the high oil content of these fish. The developed questionnaire is a valid and reliable tool for measuring fish and seafood consumption as determined by regression analysis with an independent biomarker and reliability analysis using intra-class correlation. Importantly, reliability can be maintained despite asking a high level of detail from participants. For ranking according to overall fish consumption, detailed questioning is probably not necessary, however inclusion of variables representing multiple categories of fish and seafood consumption in a regression model enables us to better account for variation in blood omega-3 PUFA levels than a single variable representing overall consumption. For the purpose of questionnaire validation, plasma phospholipid and erythrocyte membrane levels of EPA and DHA are equivalent biomarkers of fish and seafood consumption. The choice between them by future investigators will be based on more practical aspects such as convenience and the fasting state of subjects. The tangible product of this thesis is additional evidence to support a protective association between fish consumption and prostate and breast cancers, and a valid and reliable questionnaire v for measuring habitual consumption of fish and seafood in a West Australian population, that could also be applied to other populations after minor adjustment for local fish and seafood consumption patterns.