The Role Of Seipin In Lipid Metabolism And Adipogenesis
Funder
National Health and Medical Research Council
Funding Amount
$397,749.00
Summary
The prevalence of obesity and its related disorders has reached an alarming level in Australia and other developed countries. Obesity is characterized by accumulation of fully-differentiated adipocytes loaded with lipid droplets (LDs). Therefore, understanding the cellular dynamics of LDs and the molecular mechanisms of adipogenesis (adipocyte differentiation) is of crucial importance in our battle against obesity. Our proposed study will help undertand the mechnisams of obesity.
Lipoprotein Metabolism And Mutations Of The APOB Gene Causing Familial Hypobetalipoproteinaemia
Funder
National Health and Medical Research Council
Funding Amount
$396,179.00
Summary
Cardiovascular disease is an increasing problem in Australia, however, the cause of atherosclerosis is incompletely understood. A protein, known as apolipoprotein (apo) B, plays a central role in lipoprotein metabolism. Elevated levels of apoB are characteristic of many forms of hypercholestrolaemia. Familial combined hyperlipidaemia and polygenic hypercholesterolaemia are two common inherited disorders of lipoprotein metabolism that are characterised by elevated apoB levels in the blood and ear ....Cardiovascular disease is an increasing problem in Australia, however, the cause of atherosclerosis is incompletely understood. A protein, known as apolipoprotein (apo) B, plays a central role in lipoprotein metabolism. Elevated levels of apoB are characteristic of many forms of hypercholestrolaemia. Familial combined hyperlipidaemia and polygenic hypercholesterolaemia are two common inherited disorders of lipoprotein metabolism that are characterised by elevated apoB levels in the blood and early atherosclerosis. In contrast, familial hypobetalipoproteinemia is a rare inherited disorder of lipoprotein metabolism characterised by very low levels of cholesterol and apoB in the blood and resistance to atherosclerosis and cardiovascular disease. The focus of this research project is to explore the regulation of apoB metabolism using individuals from unique families with familial hypobetalipoproteinaemia. First, we will determine and characterise the alterations in the APOB gene causing the low cholesterol levels in families with familial hypobetalipoproteinaemia. Second, we will determine if these apoB alterations affect the production and-or clearance of blood fats, or lipoproteins in affected individuals, when compared to controls, by performing metabolic studies. The proposed human in vivo metabolic studies will lead to a better understanding of the mechanism(s) involved in the assembly, secretion, transport, and clearance of plasma apoB-containing lipoproteins. Furthermore, these studies may reveal new protective mechanisms and potentially aid in the development of strategies to suppress over-production of apoB-containing lipoproteins in reciprocal conditions such as familial combined hyperlipidaemia or polygenic hypercholesterolaemia.Read moreRead less
Identifying A Novel Role For Pigment Epithelium-derived Factor In Obesity-related Metabolic Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$361,637.00
Summary
Obesity is an important factor contributing to insulin resistance and type 2 diabetes; however, the factors linking these disorders are not well defined. A protein called PEDF is elevated in obesity and type 2 diabetes. This project will examine how PEDF causes insulin resistance and whether blocking PEDF's actions prevents insulin resistance. Successful completion of this project may lead to therapeutics that reduce the risk of developing type 2 diabetes.
The Role Of Endothelial Lipase In High Density Lipoprotein Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$130,550.00
Summary
Atherosclerosis is a major cause of death and disability in Australia. A high level of blood cholesterol increases the risk of developing atherosclerosis. This increase in risk is caused by the cholesterol that is carried in low density lipoproteins (LDL). However, not all cholesterol is bad. A proportion of the cholesterol in blood is carried in high density lipoproteins (HDL), which are powerful protectors against atherosclerosis. As not all HDL protect equally well against atherosclerosis, it ....Atherosclerosis is a major cause of death and disability in Australia. A high level of blood cholesterol increases the risk of developing atherosclerosis. This increase in risk is caused by the cholesterol that is carried in low density lipoproteins (LDL). However, not all cholesterol is bad. A proportion of the cholesterol in blood is carried in high density lipoproteins (HDL), which are powerful protectors against atherosclerosis. As not all HDL protect equally well against atherosclerosis, it is important to know how blood levels of HDL are regulated. In 1999 a new enzyme called endothelial lipase was discovered. Endothelial lipase dramatically decreases HDL levels in mice. The reason why this happens is not known. The main aims of this project are to work out how endothelial lipase decreases HDL levels and whether it decreases the levels of all HDL equally or whether it preferentially decreases the levels of certain types of HDL. The outcome of this project will establish how endothelial lipase affects the ability of HDL to protect against atherosclerosis in humans.Read moreRead less
Niemann Pick Disease Type C And Intracellular Sterol Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$317,741.00
Summary
Abnormal distribution of cellular cholesterol causes Nieman Pick Disease type C (NP-C), and is also strongly associated with common neurodegenerative diseases such as Alzheimer's disease. We aim to understand the molecular mechanisms by which cholesterol is sorted and transported in the cell. Our results may help develop effective therapeutic strategies against NP-C, Alzheimers' disease and other cholesterol related disorders.
The Role Of Lycopene Supplementation In The Management Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$332,875.00
Summary
Asthma is a significant and increasing health problem for Australia and is now listed as a National Health Priority Area. There is immense community interest in dietary factors affecting asthma. This project examines the potential for dietary carotenoids to be used to manage asthma. Carotenoids are antioxidants that are found in orange and red fruits and vegetables, such as tomatoes, carrots and mangoes. Research suggests that dietary carotenoids may be protective against asthma symptoms and -or ....Asthma is a significant and increasing health problem for Australia and is now listed as a National Health Priority Area. There is immense community interest in dietary factors affecting asthma. This project examines the potential for dietary carotenoids to be used to manage asthma. Carotenoids are antioxidants that are found in orange and red fruits and vegetables, such as tomatoes, carrots and mangoes. Research suggests that dietary carotenoids may be protective against asthma symptoms and -or onset. It is also likely that increasing intake of carotenoid-rich foods may be more effective than taking dietary supplements, as the key nutrients or combination of nutrients may not be known. This project will examine whether carotenoids such as lycopene can reduce the tendency of asthmatic airways to overreact to common triggers. It also investigates whether carotenoids can be used to prevent or reduce the severity of asthma attacks. The project will determine whether tomato juice or lycopene capsules are more effective in this role. This work will provide the necessary information to develop a large trial testing the ability of carotenoids to improve quality of life for people with asthma. While there is evidence to suggest that carotenoids may be helpful in asthma, the data to date is inconclusive. This study provides a scientific approach to evaluating the potential for carotenoids to be used as a treatment for asthma.Read moreRead less
Novel Metabolic Actions Of HDL With Therapeutic Potential For Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$559,471.00
Summary
Our proposal investigates a novel approach to treat type 2 (late onset) diabetes. We have identified an important link between HDL (good) cholesterol and glucose metabolism. The current proposal is to conduct studies in humans to determine whether therapies which increase HDL result in sustained reduction of blood glucose. Given the escalating global prevalence of obesity and type 2 diabetes, this work is potentially of great significance.
The Activation Of Lipoprotein Lipase By Apolipoprotein C-II
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
Abnormalities in blood lipid levels are common in our society. Treatment of these conditions adds a heavy burden to national health-care costs. Lipoprotein lipase is a plasma enzyme that plays a central role in maintaining safe blood lipid levels. The action of lipoprotein lipase in subjects on a western diet leads to the hydrolysis of about 150g of plasma triacylglycerol daily. Naturally occurring mutations in lipoprotein lipase, associated with a complete loss of enzyme activity, result in a h ....Abnormalities in blood lipid levels are common in our society. Treatment of these conditions adds a heavy burden to national health-care costs. Lipoprotein lipase is a plasma enzyme that plays a central role in maintaining safe blood lipid levels. The action of lipoprotein lipase in subjects on a western diet leads to the hydrolysis of about 150g of plasma triacylglycerol daily. Naturally occurring mutations in lipoprotein lipase, associated with a complete loss of enzyme activity, result in a high blood-lipids that can lead to premature atherosclerosis. Regulation of lipoprotein lipase occurs via an interaction with the regulatory protein apolipoprotein C-II. Individuals with apolipoprotein C-II deficiency also exhibit abnormal plasma lipid levels with an associated increased risk of coronary heart disease. These considerations demonstrate that the activation of lipoprotein lipase by apolipoprotein C-II is pivotal to the maintenance of normal blood lipid levels. The present proposal will establish the structure and orientation of apolipoprotein C-II in a lipid environment and provide a structural model for the activation of lipoprotein lipase by apolipoprotein C-II. These molecular details will serve as a model for the regulatory interactions of other apolipoproteins within lipoprotein particles and will generate leads for the development of new strategies for the treatment of blood lipid irregularities.Read moreRead less