The current obesity epidemic has intensified research on lifestyle interventions aimed at combating obesity and associated cardiovascular (CV) and metabolic risk. This clustering of risk factors with obesity is known as the “Metabolic Syndrome” (MS). There is now a large body of evidence detailing the ability of omega-3 fatty acids (n-3 FA) and regular moderate exercise to independently ameliorate several CV risk factors; however the combination of these interventions may be a more effective strategy in reducing CV risk than either treatment alone. This thesis describes the independent and combined effects of supplementation with docosahexaenoic acid (DHA) rich fish oil, and regular moderate exercise, on CV, metabolic and inflammatory biomarkers. Sedentary, overweight volunteers (BMI > 25kg/m2) with mild hypertension (140/90 – 160/100mmHg), elevated plasma triglycerides (TAG) (>1.6mmol/L) or elevated total cholesterol (TC) (>5.5mmol/L) were recruited in three cohorts for a 12-week intervention trial. Subjects were randomised to one of the following interventions: fish oil, fish oil and exercise, sunflower oil (placebo), sunflower oil and exercise. Subjects consumed 6 g/day of DHA-rich fish oil (26% DHA, 6% EPA; ~1.9g n-3 FA) or sunflower oil. The exercise groups walked 3 days/wk for 45 min, at 75% age-predicted maximal heart rate (HR). Outcome measures were assessed and compared across each intervention group at Weeks 0, 6 and 12, with the exception of body composition, heart rate variability (HRV) and immune functions, which were assessed at Weeks 0 and 12 only. Apart from the consumption of allocated capsules, all subjects were instructed to maintain their normal diet during the study. If not asked to exercise as part of the intervention subjects were also instructed to maintain their normal level of physical activity. Supplementation with DHA rich fish oil resulted in substantial increases in total long chain n-3 FA and DHA levels in erythrocyte membranes, accompanied by reduction of TAG, increase of high-density lipoprotein (HDL) cholesterol and reduction of superoxide production by stimulated neutrophils. Both the increase in HDL and the decrease in superoxide production were correlated with the change in erythrocyte DHA. Endothelium dependent arterial vasodilation (assessed by flow-mediated dilatation, FMD), HRV and HR response to exercise were also improved in subjects supplemented with the DHA-rich fish oil. Regular moderate intensity exercise, either alone or in addition to the DHA-rich fish oil supplementation, had no effect on these parameters, although it improved the compliance of small resistance arteries. Interestingly, however, both DHA-rich fish oil and regular exercise reduced body fat and these effects were additive when the interventions were combined. The change in fat mass was accompanied by an increase in fat oxidation during exercise, as measured by the respiratory exchange ratio. For the population as a whole, reductions in total and abdominal fat mass were associated with reductions in blood pressure. In summary, this study is the first to evaluate the metabolic and CV benefits that can be achieved by combining n-3 FA supplementation from fish oil and regular aerobic exercise in overweight/obese adults. While this combination did not produce any synergistic effects, several independent benefits were attained. The high compliance rate (>85%) within this study indicates that this intervention is well tolerated and may therefore be sustainable in the longer term. Future research should evaluate the mechanisms underlying the n-3 FA - mediated improvements in body composition. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1283720 / Thesis (PhD) -- School of Molecular and Biomedical Science, 2007

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

From animal experimentation, and studies using in vitro models, there was evidence in the literature to suggest that dietary fibre may influence contractility and motility of the gastrointestinal tract and long chain (LC) n-3 polyunsaturated fatty acids (PUFAs) from marine sources may influence contractility of smooth muscle cells in blood vessels. The hypothesis of this thesis was that dietary fish oil and/or fibre influence the contractility of isolated intact sections of gut smooth muscle tissue from small animal models. Methodology was established to measure in vitro contractility of intact pieces of guinea pig ileum with the serosal side isolated from the lumen. It was demonstrated that four amino acid peptides from κ-casein (casoxins) applied to the lumen overcame morphine-induced inhibition of contraction. Using this established technology, the guinea pig was used to investigate the effects of dietary fibre and fish oil supplementation on gut in vitro contractility. In separate experiments, changes in sensitivity to electrically-driven and 8-iso-prostanglandin (PG)E₂-induced contractility were demonstrated for dietary fibre and fish oil. A modified, isolated gut super-perfusion system was then established for the rat to validate these findings. It was subsequently shown that LC n-3 PUFA from dietary fish oil significantly increased maximal contraction in response to the G-protein coupled receptor modulators, acetylcholine and the eicosanoids PGE₂, PGF₂α, 8-iso-PGE₂ and U-46619 in ileum but not colon, without changes in sensitivity (EC₅₀), when n-3 PUFA as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) had been incorporated to a similar degree into the gut total phospholipid membrane pool. It was further established that the spontaneously hypertensive rat (SHR) had a depressed prostanoid (PGE₂and PGF₂α) response in the gut that could be restored by dietary fish oil supplementation (5% w/w of total diet) in the ileum but not the colon. Importantly, the muscarinic response in the colon of the SHR was increased by fish oil supplementation with DHA likely to be the active agent. Dietary fish oil dose experiments deduced differential increases in response occurred at fish oil concentrations of 1% for muscarinic and 2.5% (w/w) for prostanoid stimulators of the ileum with no difference in receptor-independent KCl-induced depolarization-driven contractility. Studies combining high amylose resistant starch (HAMS, 10% w/w) and fish oil (10% w/w) fed to young rats demonstrated a low prostanoid response that was enhanced by dietary fish oil but not resistant starch. There was however, an interactive effect of the HAMS and fish oil noted for the muscarinic-mimetic, carbachol. Generally, resistant starch increased the large bowel short chain fatty acid pool with a subsequent lower pH. Binding studies determined that while the total muscarinic receptor binding properties of an isolated ileal membrane fraction were not affected in mature rats by dietary fish oil, young rats had a different order of muscarinic receptor subtype response with a rank order potency of M₃ > M₁ > M₂ compared to mature animals of M₃ > M₂ > M₁ with fish oil altering the sensitivity of the M₁ receptor subtype in isolated carbachol-precontracted ileal tissue. In conclusion, experiments using the guinea pig and rat gut models demonstrated that dietary fish oil supplementation, and to a lesser degree fibre, increased receptor-driven contractility in normal and compromised SHR ileum and colon. Further, changes in responsiveness were demonstrated in the developing rat gut prostanoid and muscarinic receptor populations that could be altered by dietary fish oil. Preliminary evidence suggested that fish oil as DHA may alter receptor-driven gut contractility by mechanisms involving smooth muscle calcium modulation. Defining the role that dietary fibre and fish oil, and other nutrients, play in normal and diseased states of bowel health such as inflammatory bowel disease (IBD), where contractility is compromised, are among the ongoing challenges. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1316907 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2008

From animal experimentation, and studies using in vitro models, there was evidence in the literature to suggest that dietary fibre may influence contractility and motility of the gastrointestinal tract and long chain (LC) n-3 polyunsaturated fatty acids (PUFAs) from marine sources may influence contractility of smooth muscle cells in blood vessels. The hypothesis of this thesis was that dietary fish oil and/or fibre influence the contractility of isolated intact sections of gut smooth muscle tissue from small animal models. Methodology was established to measure in vitro contractility of intact pieces of guinea pig ileum with the serosal side isolated from the lumen. It was demonstrated that four amino acid peptides from κ-casein (casoxins) applied to the lumen overcame morphine-induced inhibition of contraction. Using this established technology, the guinea pig was used to investigate the effects of dietary fibre and fish oil supplementation on gut in vitro contractility. In separate experiments, changes in sensitivity to electrically-driven and 8-iso-prostanglandin (PG)E₂-induced contractility were demonstrated for dietary fibre and fish oil. A modified, isolated gut super-perfusion system was then established for the rat to validate these findings. It was subsequently shown that LC n-3 PUFA from dietary fish oil significantly increased maximal contraction in response to the G-protein coupled receptor modulators, acetylcholine and the eicosanoids PGE₂, PGF₂α, 8-iso-PGE₂ and U-46619 in ileum but not colon, without changes in sensitivity (EC₅₀), when n-3 PUFA as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) had been incorporated to a similar degree into the gut total phospholipid membrane pool. It was further established that the spontaneously hypertensive rat (SHR) had a depressed prostanoid (PGE₂and PGF₂α) response in the gut that could be restored by dietary fish oil supplementation (5% w/w of total diet) in the ileum but not the colon. Importantly, the muscarinic response in the colon of the SHR was increased by fish oil supplementation with DHA likely to be the active agent. Dietary fish oil dose experiments deduced differential increases in response occurred at fish oil concentrations of 1% for muscarinic and 2.5% (w/w) for prostanoid stimulators of the ileum with no difference in receptor-independent KCl-induced depolarization-driven contractility. Studies combining high amylose resistant starch (HAMS, 10% w/w) and fish oil (10% w/w) fed to young rats demonstrated a low prostanoid response that was enhanced by dietary fish oil but not resistant starch. There was however, an interactive effect of the HAMS and fish oil noted for the muscarinic-mimetic, carbachol. Generally, resistant starch increased the large bowel short chain fatty acid pool with a subsequent lower pH. Binding studies determined that while the total muscarinic receptor binding properties of an isolated ileal membrane fraction were not affected in mature rats by dietary fish oil, young rats had a different order of muscarinic receptor subtype response with a rank order potency of M₃ > M₁ > M₂ compared to mature animals of M₃ > M₂ > M₁ with fish oil altering the sensitivity of the M₁ receptor subtype in isolated carbachol-precontracted ileal tissue. In conclusion, experiments using the guinea pig and rat gut models demonstrated that dietary fish oil supplementation, and to a lesser degree fibre, increased receptor-driven contractility in normal and compromised SHR ileum and colon. Further, changes in responsiveness were demonstrated in the developing rat gut prostanoid and muscarinic receptor populations that could be altered by dietary fish oil. Preliminary evidence suggested that fish oil as DHA may alter receptor-driven gut contractility by mechanisms involving smooth muscle calcium modulation. Defining the role that dietary fibre and fish oil, and other nutrients, play in normal and diseased states of bowel health such as inflammatory bowel disease (IBD), where contractility is compromised, are among the ongoing challenges. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1316907 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2008