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Effect Of Lipid Mediators And Dietary Fats In Bone Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$380,250.00
Summary
Osteoporosis in a major public health problem which directly affects about 10% of the population, which is currently around 2 million Australians. With aging of the population, it is projected that this proportion will increase to more than 13% over the next 20 years. When it is considered that the direct hospital and residential care costs attributable to osteoporotic fractures currently approaches $2 billion per annum, low-cost interventions for increasing bone strength which are easily applie ....Osteoporosis in a major public health problem which directly affects about 10% of the population, which is currently around 2 million Australians. With aging of the population, it is projected that this proportion will increase to more than 13% over the next 20 years. When it is considered that the direct hospital and residential care costs attributable to osteoporotic fractures currently approaches $2 billion per annum, low-cost interventions for increasing bone strength which are easily applied to the elderly population have enormous potential for health benefits in Australia. Thus study will examine the effects of dietary omega-3 fats, of the kind found in fish and fish oil, on the biology of bone metabolism and on bone strength. The results will provide information which may be used in developing simple drug or dietary strategies for large-scale use for increasing bone mass and strength in the elderly population. A strength of the study arises from the combination of research expertise in (a) dietary fats, and (b) molecular biology of bone cells, and (c) animal models of bone metabolism which are amenable to dietary interventions. This combination is unique, but builds on well established systems which hitherto have existed in separate research paradigms. The Chief Investigator has considerable experience in development of diets enriched in omega-3 fats which are practical and suitable for daily use on a long-term basis. This adds considerably to the potential significance of the outcomes because, if favourable effects of omega-3 fats are observed and are characterised with regard to mechanisms, the results can be rapidly translated into large-scale clinical use.Read moreRead less
Effects Of N-3 Polyunsaturated Fatty Acids On Post Surgical Atrial Fibrillation: A Prospective Randomised Study
Funder
National Health and Medical Research Council
Funding Amount
$536,529.00
Summary
Consumption of fish and fish oil has been associated with protective effects for deaths from heart disease in many studies. The effects are consistent and quite strong and appear to be unrelated to blood cholesterol levels. The effects are more likely due to the possibility that fish oil, which contains n-3 fats, can suppress abnormal heart rhythms which can cause 'sudden cardiac death'. This has been shown in animal studies, and recently we have shown that they can also suppress abnormal heart ....Consumption of fish and fish oil has been associated with protective effects for deaths from heart disease in many studies. The effects are consistent and quite strong and appear to be unrelated to blood cholesterol levels. The effects are more likely due to the possibility that fish oil, which contains n-3 fats, can suppress abnormal heart rhythms which can cause 'sudden cardiac death'. This has been shown in animal studies, and recently we have shown that they can also suppress abnormal heart rhythms in humans. Patients undergoing coronary bypass surgery are particularly susceptible to abnormal heart rhythms in the upper chambers of the heart in the days immediately following surgery. While these abnormal rhythms are rarely life threatening, they can result in increased post-surgical complications and a longer hospital stay with associated increased costs to the health system. In this study we will determine whether providing high dose fish oil for 3 weeks immediately preceding coronary bypass surgery, will result in a reduction in the proportion of patients experiencing post-surgical abnormal heart rhythms. We will also examine the effects of n-3 fats on the incidence of other complications following bypass surgery and also the length of hospital stay. In addition, we will gather data which will provide insight into the mechanisms by which n-3 fatty acids produce their well documented benefits to patients with cardiovascular disease. The significance of this study is its ability to provide a protective strategy in heart disease in which the mechanism is understood, which is effective, and importantly, which will have the potential to provide savings to the health care system through a reduction in hospital stay.Read moreRead less
The Effect Of Dietary Fatty Acids On Cellular Calcium Handling Mechanisms In Cardiac Muscle
Funder
National Health and Medical Research Council
Funding Amount
$275,765.00
Summary
A major health problem in the developed countries is cardiovascular disease, which is manifest as high blood pressure, stroke, heart attack and abnormalities of heart rhythm, or cardiac arrhythmias. A western diet, ie. one high in animal fat, or saturated fats, may be to blame. Human epidemiological studies have shown that consumption of a diet high in saturated fats is correlated with a propensity to arrhythmias while a diet high in polyunsaturated fatty acids (PUFAs) can confer protection from ....A major health problem in the developed countries is cardiovascular disease, which is manifest as high blood pressure, stroke, heart attack and abnormalities of heart rhythm, or cardiac arrhythmias. A western diet, ie. one high in animal fat, or saturated fats, may be to blame. Human epidemiological studies have shown that consumption of a diet high in saturated fats is correlated with a propensity to arrhythmias while a diet high in polyunsaturated fatty acids (PUFAs) can confer protection from coronary heart disease and cardiac arrhythmias. The mechanisms underlying these effects are not fully understood. The contraction of the heart depends on changes in calcium inside the individual muscle cells. Abnormalities of the way calcium is handled in the cells leads to abnormalities of contraction and to a certain types of arrhythmia. Over the last 5 to 10 years, technological developments have enabled us to examine changes in calcium in living heart cells at microscopic level. It is possible to fill individual living cells with a fluorescent dye which changes either the magnitude or the wavelength of its fluorescence according to the ambient calcium concentration. Cells filled with these dyes are examined with a laser scanning confocal microscope, in which a very tightly focussed laser beam excites the dye and the resulting fluorescence is gathered by a computer controlled image analysis system. In this way we can measure the calcium concentration within the cells with a spatial resolution of about 1-1000 of a millimetre, and a time resolution of about 1-100 of a second. Using these techniques, we have found that supplementing the diet of rats with either PUFAs or saturated fats produces a dramatic change in the way that calcium is stored and released in their heart cells. This effect of dietary fats has not been reported before, and it may represent an important clue as to how these substances protect against many cardiac arrhythmias.Read moreRead less
N-3 LCPUFA Supplementation In Pregnancy To Reduce Allergies In Early Childhood
Funder
National Health and Medical Research Council
Funding Amount
$813,423.00
Summary
Over the last 20 years there has been a dramatic increase in allergic diseases in Australia as well as many other industrialised countries. This may be due to changes in our environment or diet. Over this period of time there has also been an increase in the dietary intake of n-6 fatty acids from vegetable oils and a corresponding decline in the intake of n-3 fatty acids from fish. Studies now indicate that there is a plausible link between these dietary changes and allergic diseases. Furthermor ....Over the last 20 years there has been a dramatic increase in allergic diseases in Australia as well as many other industrialised countries. This may be due to changes in our environment or diet. Over this period of time there has also been an increase in the dietary intake of n-6 fatty acids from vegetable oils and a corresponding decline in the intake of n-3 fatty acids from fish. Studies now indicate that there is a plausible link between these dietary changes and allergic diseases. Furthermore, emerging data suggest that the potential benefits of increasing n-3 fatty acids may be greatest during pregnancy and before allergic responses are established. Our project aims to minimise allergies in children from families where at least one parent has an allergy. We will assess whether dietary n-3 fatty acid supplementation of pregnant women will result in fewer children with allergies at 1 and 3 years of age. If the proposed intervention is successful, it would be a safe, cheap, acceptable and effective strategy to prevent allergies in children at high risk.Read moreRead less
Immunomodulatory Effects Of Omega-3 Polyunsaturated Fatty Acids : Role In Allergy Prevention In Infancy
Funder
National Health and Medical Research Council
Funding Amount
$537,600.00
Summary
The dramatic increase in asthma and allergic disease over the last 20-30 years has highlighted the urgent need to identify associated environmental changes that may also be logical targets for disease prevention. Although this is likely to be multifactorial, one significant change during this period has been a progressive decline in the intake of dietary anti-inflammatory n-3 polyunsaturated fats (PUFA) in Western diets, with a corresponding increase in n-6 PUFA fatty acids. We recently showed f ....The dramatic increase in asthma and allergic disease over the last 20-30 years has highlighted the urgent need to identify associated environmental changes that may also be logical targets for disease prevention. Although this is likely to be multifactorial, one significant change during this period has been a progressive decline in the intake of dietary anti-inflammatory n-3 polyunsaturated fats (PUFA) in Western diets, with a corresponding increase in n-6 PUFA fatty acids. We recently showed for the first time that n-3 PUFA may have more significant effects in very early life before immune responses are fully established. We confirmed that maternal fish oil supplementation (n-40) resulted in significantly higher n-3 PUFA levels in newborns (compared to those with no supplements, n-43), and this was related to reduced immune responses to allergens (such as house dust mite, cat and egg). These observations suggest that n-3 PUFA can modify early immune development. Although this previous study was designed to assess immune outcomes (rather than clinical outcomes) we collected preliminary clinical data for the purposes of this application. We observed a consistent trend for less allergic symptoms and sensitisation in the supplementation group. These observations clearly warrant this proposed study to confirm these clinical effects, and to assess the mechanisms of action in considerably more detail. In this proposed study we will compare the effects of fish oil (n-165) or placebo (n-165) in early infancy (from 0-6 months of age). This much larger population will allow us to determine if increasing dietary n-3 PUFA is a way of reducing the chance of allergy in families where there is a high genetic risk. Approximately 40% of infants in Australia will go on to develop asthma or allergies. Strategies such as this that reduce the risk (even slightly) or the severity of disease expression could have enormous impact in this global context at relatively little cost.Read moreRead less
Regulation And Activity Of Fatty Acid Delta-6 Desaturase (D6D)
Funder
National Health and Medical Research Council
Funding Amount
$527,683.00
Summary
Fish and fish oils contain fats known as omega-3 fats. These have health benefits in adult conditions such as rheumatoid arthritis and heart disease, and they are necessary for proper brain and eye development in infants. However, much of the population does not like to eat fish and also, world fish stocks are under stress. Thus, a sustainable alternative source of omega-3 fats needs to be explored. Some vegetable oils such as canola, echium, and flaxseed oils have omega-3 fats. However, these a ....Fish and fish oils contain fats known as omega-3 fats. These have health benefits in adult conditions such as rheumatoid arthritis and heart disease, and they are necessary for proper brain and eye development in infants. However, much of the population does not like to eat fish and also, world fish stocks are under stress. Thus, a sustainable alternative source of omega-3 fats needs to be explored. Some vegetable oils such as canola, echium, and flaxseed oils have omega-3 fats. However, these are not the same as the omega-3s in fish oil. In general, vegetable omega-3s are known as short-chain omega-3s whereas those in fish are long-chain. When the vegetable oil omega-3s are consumed in the diet, the body must convert them to the fish-type, or long-chain, omega-3s in order to gain the health benefits. Currently, human metabolism is poor at doing this conversion. Our studies suggest that the amounts and blends of fats in most diets are well below optimal for conversion to long-chain omega-3s in the body. In particular, our studies show that there may be no point in simply adding more vegetable omega-3 fats to the diet. This project will examine the enzymes that convert the short-chain to the long-chain omega-3 fats. In particular, it will examine how the dietary fats interact with each other in detrimental ways to suppress activity of the conversion enzymes necessary for long-chain omega-3 formation. Evidence for the health benefits of fish-based omega-3 fats is very strong and it is an approach to health that most people can undertake on their own. Our lack of knowledge of the best way to use plant-based omega-3 fats is a large impediment for a more sustainable and broader based use of omega-3 fats. The results from this study will begin to fill in this knowledge gap. The results will be useful across a range of activities that are determinants of the kinds of fat that we eat. These include oil seed breeding, food manufacture, and dietetics.Read moreRead less
Effects Of Omega-3 Fatty Acids And Coenzyme Q10 On Cardiovascular Risk In Chronic Renal Failure
Funder
National Health and Medical Research Council
Funding Amount
$433,725.00
Summary
Heart disease is one of the main causes of death in Australia. People with chronic renal failure (CRF) are at increased cardiovascular risk due to the coexistence of hypertension (high blood pressure), blood lipid abnormalities, and increased inflammation and oxidative stress. One approach may be to complement drug treatment of CRF with non-drug measures such as nutrition and lifestyle factors. In this regard, omega-3 fatty acids have great clinical potential in the treatment of CRF and its asso ....Heart disease is one of the main causes of death in Australia. People with chronic renal failure (CRF) are at increased cardiovascular risk due to the coexistence of hypertension (high blood pressure), blood lipid abnormalities, and increased inflammation and oxidative stress. One approach may be to complement drug treatment of CRF with non-drug measures such as nutrition and lifestyle factors. In this regard, omega-3 fatty acids have great clinical potential in the treatment of CRF and its associated complications. Omega-3 fatty acids reduce blood pressure and blood vessel wall elasticity, they improve blood fats, reduce the tendency of blood to clot, and attenuate inflammation and oxidative stress. Coenzyme Q10 is an antioxidant that plays a critical role in cellular function. It improves blood pressure, blood vessel and heart function, and glucose control. It is proposed that the impact of a combined approach of supplementation of omega-3 fatty acids given as fish oils and coenzyme Q10, will lead to beneficial composite effects on blood pressure and heart disease risk in patients with mild-to-moderate chronic renal failure. In the proposed study, patients will undergo medical and biochemical assessment during a 3-week baseline period, after which they will be allocated to either supplement their normal diet with either 4g of encapsulated fish oil or placebo per day. Within each of these groups they will be further assigned to take coenzyme Q10 capsules (200mg) or placebo capsules. All measurements will be repeated at the end of 8 weeks.Read moreRead less
Testing The Effect Of Long-chain Omega-3 Polyunsaturated Fatty Acids On Cognitive Ageing In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$738,908.00
Summary
The ageing profile of our population holds challenges for society, with some of the major impact due to loss of independence and quality of life in older people, arising from decline in cognitive functioning. Evidence suggests a benefit of Omega-3 fatty acids on cognitive functioning in older people but claims that Omega-3 slows cognitive decline have not been adequately tested. This study tests the effect of Omega-3 supplementation on cognition in healthy older people, over an 18-month period.
Dilinoleoyl Phosphatidic Acid As A Novel Mediator Of Insulin Resistance In Muscle
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
We have identified a novel fat molecule in muscle which may play an important role in causing insulin resistance during obesity, a major factor in the development of Type 2 diabetes. We will now examine whether depletion of this molecule, dilinoleoyl-phosphatidic acid, can improve insulin action in muscles and in obese mice, and investigate the mechanisms by which it may act. This work may indicate new strategies for the treatment of diabetes.