Peroxisome Proliferator-activated Receptors: A Role In The Promotion Of Mammary Gland Carcinogenesis By Dietary Fat.
Funder
National Health and Medical Research Council
Funding Amount
$188,702.00
Summary
Breast cancer is a leading cause of death in Australian women. While some women have a hereditary predisposition to breast cancer, for most women a variety of factors are responsible for their disease. One thing that appears to be important as a cause of breast cancer is our diet. There are many components of the diet that may play a role. One important factor is the amount and type of fat that we consume. Just how dietary fat causes an increase in breast cancer is not known. What this project a ....Breast cancer is a leading cause of death in Australian women. While some women have a hereditary predisposition to breast cancer, for most women a variety of factors are responsible for their disease. One thing that appears to be important as a cause of breast cancer is our diet. There are many components of the diet that may play a role. One important factor is the amount and type of fat that we consume. Just how dietary fat causes an increase in breast cancer is not known. What this project aims to achieve is an understanding of how dietary fat and breast cancer are related. If we can understand this then we can rationally design treatments or a preventative strategy.Read moreRead less
The Role Of Stress Response And Circadian Genes In The Link Between Excess Lipid And Muscle Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$579,000.00
Summary
Obesity and its associated conditions of heart disease, reduced insulin action, fatty liver and type 2 diabetes are increasing at an alarming rate worldwide. The epidemic of these conditions appears to be due to an interaction between genetic background and changes in the environment such as reduced physical activity and increased availability and consumption of high energy food. The relationship between genes and environment is very complex but it seems clear that increased intake of high fat f ....Obesity and its associated conditions of heart disease, reduced insulin action, fatty liver and type 2 diabetes are increasing at an alarming rate worldwide. The epidemic of these conditions appears to be due to an interaction between genetic background and changes in the environment such as reduced physical activity and increased availability and consumption of high energy food. The relationship between genes and environment is very complex but it seems clear that increased intake of high fat foods can cause body tissues to accumulate excess fat. This interferes with the way that the hormone insulin controls body glucose utilisation although how this happens has not been fully defined. This grant application will test two possible mechanisms that could help explain the link between increased dietary fat intake and decreased insulin action in muscle. Using microarrays to examine the activity of genes in normal and insulin resistant muscle, we have identified two groups of genes that may be involved in how fat causes insulin resistance. One group of genes is normally associated with stress and we will determine if fats control these genes directly or if fats increase other stress factors which increase the activity of these genes. We will then use novel gene therapy techniques to see if these genes cause insulin resistance in muscle of experimental animals. The second group of genes is related to the mechanisms which regulate daily cycles in the body such as sleep-wake cycles, blood pressure, and eating behaviour. We will examine the activity of these genes over a 24 hour period in muscle from normal animals and insulin resistant animals to determine if disruption of these gene cycles contributes to insulin resistance. We will then perform experiments to establish what processes these genes control. The successful outcome of this grant will determine if these groups of genes can be targeted to help treat lipid-induced insulin resistance in muscle.Read moreRead less
Therapeutic Regulation Of Hepatic Steatosis And Lipid Transport In The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$522,435.00
Summary
Obesity is an increasing problem in Australia. Elevated fat levels in the liver and blood are associated with obesity and increased risk for heart disease. In this project, we will demostrate new mechanisms of action of Pioglitazone (an insulin-sensitizing agent) and Omacor (fish oils) that will complement the favourable efect of weight loss in the treatment of elevated blood fats and reduction in risk of heart disease in an important groups of subject in the population.
Dietary Protein-induced DNA Damage In Colon And Consequences For Colorectal Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$604,797.00
Summary
This research will explore the effects of dietary protein on genetic damage to cells lining the large bowel and risk of developing colorectal cancer. We will determine the degree and type of DNA damage resulting from increased protein, the cellular response to this DNA damage, whether it increases risk for developing bowel cancer and whether it can be minimised by other foods in both an animal model and humans.
Obesity Induced By Chronic High-Energy Diet: Central Influences In Development And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$221,210.00
Summary
This project is about the study of central regulation of energy balance contributing to prevention or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and economically. Development of human obesity and its related metabolic disorders generally develops over a long period and eventually becomes a chroni ....This project is about the study of central regulation of energy balance contributing to prevention or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and economically. Development of human obesity and its related metabolic disorders generally develops over a long period and eventually becomes a chronic condition. Generally, chronic consumption of high-energy food in excess of expenditure leads to excessive fat accumulation and promotes the development of obesity. However, under these conditions, some individuals become obese, while others remain lean indicating that variation in susceptibility is an important determinant of the development of obesity. It is apparent that those individuals resistant to obesity have a more effective defence system against excessive fat accumulation. Using the animal models developed in our laboratory, the proposed research aims to search for the differences in the central regulation between the mice resistant or susceptible to the development of obesity. The outcomes we expect to achieve include: 1) better understanding of central factors controlling energy balance, 2) clarification of the central factors responsible for dysregulation of this system by chronic consumption of a high-energy diet, and 3) identification of those factors contributing to prevention against such dysregulation. Further, according to our previous study [XFH1, 2, 3], we propose to use the drugs targeting on the specific receptor subtypes to test reversibility of chronic high energy diet-induced obesity.Read moreRead less