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Insulin As A Regulator Of Postprandial Lipaemia In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$226,097.00
Summary
People who are overweight often develop cardio- and peripheral-vascular disease. The reasons are multifactorial but usually involve disturbances in the metabolism of fats. Overweight subjects have a tendency to accumulate energy rich lipids in blood derived from the gut or from the liver. Chronic arterial exposure to these lipids leads to an accumulation of certain types of fats in the wall of blood vessels, which if unabated ultimately leads to an impediment in blood flow. Ongoing studies in ou ....People who are overweight often develop cardio- and peripheral-vascular disease. The reasons are multifactorial but usually involve disturbances in the metabolism of fats. Overweight subjects have a tendency to accumulate energy rich lipids in blood derived from the gut or from the liver. Chronic arterial exposure to these lipids leads to an accumulation of certain types of fats in the wall of blood vessels, which if unabated ultimately leads to an impediment in blood flow. Ongoing studies in our laboratory have found that in obesity the production of these fats and the clearance is disturbed probably because of an inability to properly respond to insulin. The hormone insulin critically regulates synthesis, secretion and clearance of lipids, however, in obese subjects the concentration of insulin is abnormally elevated. We have explored the impact of sustained weight reduction on the production and clearance of lipids from blood. Collectively, weight loss leads to an improvement in fat metabolism because of increased sensitivity to the normal effects of insulin. However, weight reduction alone is rarely able to fully correct the disturbances in fat metabolism and it is likely that the individuals are still at risk of developing vascular disease. In this proposal, we wish to explore the efficacy of two agents which could potentially ameliorate lipid disturbances in diabetes by enhancing the regulatory effects of insulin. We believe that long term correction of the lipid abnormalities in obesity will reduce the frequency and progression of cardio- and peripheral-vascular disease.Read moreRead less
The Role Of Apolipoprotein E In High Density Lipoprotein Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$151,208.00
Summary
Coronary heart disease is a major cause of death and disability in Australia. A high level of blood cholesterol increases the risk of developing coronary heart disease. This increase in coronary 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 high density lipoproteins (HDL), which are powerful protectors against heart disease. People with high blood levels of HDL have a s ....Coronary heart disease is a major cause of death and disability in Australia. A high level of blood cholesterol increases the risk of developing coronary heart disease. This increase in coronary 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 high density lipoproteins (HDL), which are powerful protectors against heart disease. People with high blood levels of HDL have a significantly reduced risk of developing heart disease. HDL consist of several different types of particles that contain lipids (or fats) and proteins. Not all HDL protect equally against coronary heart disease. Our ability to determine which HDL are the most cardioprotective is limited because it is difficult to separate the different types of particles from each other. One thing we do know is that the cardioprotective properties and metabolism of HDL are influenced by the proteins they contain. A considerable amount is known about the effects of the two main HDL proteins on the metabolism and cardioprotective properties of HDL. However, HDL contain several other proteins which are also important in this regard. This project is concerned with one of those other proteins called apolipoprotein E. The evidence that apolipoprotein E protects against heart disease is indisputable. Despite this, almost nothing is known about its role in HDL metabolism. This is because it is difficult to isolate large amounts of apolipoprotein E-containing HDL from plasma. In order to overcome these problems I have developed a novel method for preparing HDL which contain apolipoprotein E. These preparations are comparable to the apoE-containing HDL in human plasma. They will be used in this project to study the influence of apolipoprotein E on HDL metabolism.Read moreRead less