IMPAIRED REGULATION OF CYTOCHROMES P450 DURING THE EVOLUTION OF HEPATIC STEATOSIS
Funder
National Health and Medical Research Council
Funding Amount
$186,740.00
Summary
The accumulation of fat in liver is a common problem in early liver injury caused by alcohol, certain drugs and diseases like diabetes. When this occurs the fats can change the amounts of a number of genes and proteins in liver. Cytochrome P450 proteins insert an activated form of oxygen into chemicals, including drugs and fats. In the process, however, some of these activated chemicals can damage surrounding tissues. This project will study the details of how the levels of cytochromes P450 are ....The accumulation of fat in liver is a common problem in early liver injury caused by alcohol, certain drugs and diseases like diabetes. When this occurs the fats can change the amounts of a number of genes and proteins in liver. Cytochrome P450 proteins insert an activated form of oxygen into chemicals, including drugs and fats. In the process, however, some of these activated chemicals can damage surrounding tissues. This project will study the details of how the levels of cytochromes P450 are altered when fat accumulates in liver. The findings may suggest ways in which normal levels of cytochromes P450 can be restored and how to minimise the injurious effects of activated chemicals in liver.Read moreRead less
The Role Of Muscle Fatty Acid Oxidation In Regulating Intramyocellular Lipid Accumulation.
Funder
National Health and Medical Research Council
Funding Amount
$169,695.00
Summary
Obesity and the subsequent accumulation of fat in muscle leads to reduced insulin action and an increased risk of type 2 diabetes. This project will investigate the metabolic processes that influence fat accumulation and oxidation primarily in skeletal muscle, the tissue responsible for most fuel utilization in the body. This information will help design therapeutic strategies to prevent the development of type 2 diabetes.
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
Fatty Acid Biosynthesis In The Malaria Chloroplast As A Drug Target
Funder
National Health and Medical Research Council
Funding Amount
$131,035.00
Summary
Malarial parasites contain a chloroplast similar to that of plants. We recently found genetic evidence suggesting the malaria chloroplast makes fats in the same way as plant chloroplasts. Additionally, we have found that drugs and herbicides that block plant chloroplast fat production stop growth of malaria cultures. Parasitologists had assumed that malaria was unable to make fats and would scavenge them from its human host so we have probably discovered a new metabolic pathway in these parasite ....Malarial parasites contain a chloroplast similar to that of plants. We recently found genetic evidence suggesting the malaria chloroplast makes fats in the same way as plant chloroplasts. Additionally, we have found that drugs and herbicides that block plant chloroplast fat production stop growth of malaria cultures. Parasitologists had assumed that malaria was unable to make fats and would scavenge them from its human host so we have probably discovered a new metabolic pathway in these parasites. We now propose to prove that the drugs work by blocking essential, chloroplast-based fat production in parasites. This could lead to novel treatment of malaria and related parasites.Read moreRead less
Inhibition Of Glucose-stimulated Insulin Secretion By Protein Kinase C Epsilon
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
Type 2 diabetes is a chronic disease which occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and is strongly linked to obesity. We have discovered that fat oversupply activates an enzyme in the pancreas causing defects in insulin release due to glucose. Inhibiting this enzyme helps overcome diabetes, through poorly defined mechanisms that we aim to clarify here. Our work could lead to new therapies for diabetes.
Mechanisms Of Fatty-acid Mediated Destruction Of Pancreatic Beta Cells
Funder
National Health and Medical Research Council
Funding Amount
$510,476.00
Summary
Type 2 diabetes is associated with obesity, but not all obese individuals develop the disease. Non-diabetic obese subjects are able to compensate for diminished sensitivity to insulin (a general feature of obesity) by enhanced output of insulin from the pancreatic beta-cells of the islet of Langerhans. In diabetics this compensatory mechanism is disrupted. Obesity and Type 2 diabetes are also associated with elevated levels of fatty acids (FAs) in the bloodstream. These can be taken up by the be ....Type 2 diabetes is associated with obesity, but not all obese individuals develop the disease. Non-diabetic obese subjects are able to compensate for diminished sensitivity to insulin (a general feature of obesity) by enhanced output of insulin from the pancreatic beta-cells of the islet of Langerhans. In diabetics this compensatory mechanism is disrupted. Obesity and Type 2 diabetes are also associated with elevated levels of fatty acids (FAs) in the bloodstream. These can be taken up by the beta-cells where they exert both short and long-term effects. In the longer term FAs can be toxic to beta-cells and this is thought to be important in the failure of beta-cell compensation. The project is aimed at a better understanding of the manner by which different types of FAs influence the susceptibility of beta-cells to destruction. It builds on our preliminary results suggesting that the capacity of the beta-cell to convert saturated FAs to unsaturated FAs helps protect them from destruction. Our aim is to examine the mechanisms underlying this protection.Read moreRead less