LKB1 - The Link Between Obesity And Breast Cancer In Postmenopausal Women
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Obesity is a worldwide epidemic affecting 60% of Australians and is linked to many diseases including breast cancer. Changes in sex hormone levels during menopause may cause these diseases. The focus of this proposal is to determine the role of the sex hormones to regulate a protein (LKB1) involved in both fat metabolism and cancer. This research will benefit the ageing population by making a contribution toward generating therapeutics to combat obesity and breast cancer.
Sex Differences In The Mechanisms By Which Stress Inhibits The Secretion And Actions Of GnRH
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
It is well known that stress can impair reproduction in humans and animals but it is not understood how this occurs. Consequently there are no therapies available to overcome the detrimental effects of stress on reproduction. Stress can take many forms, such as psychological stress, surgical trauma, strenuous exercise, undernutrition, all of which may inhibit reproduction. We now know that males and females respond differently to stress and we have shown that stress is also likely to have differ ....It is well known that stress can impair reproduction in humans and animals but it is not understood how this occurs. Consequently there are no therapies available to overcome the detrimental effects of stress on reproduction. Stress can take many forms, such as psychological stress, surgical trauma, strenuous exercise, undernutrition, all of which may inhibit reproduction. We now know that males and females respond differently to stress and we have shown that stress is also likely to have different effects on reproduction in males and females. In this project we aim to determine how stress impairs reproduction in males and females. A major effect of stress appears to be to inhibit the secretion of a substance produced by the brain that is necessary for the regulation of reproduction. This substance is called gonadotrophin releasing hormone (GnRH) and it acts on a small gland at the base of the brain to cause the release of hormones that are essential for reproduction in both males and females. It is also possible that stress may inhibit the actions of GnRH. Our research suggests that there may be differences between males and females in the extent to which stress inhibits the secretion of GnRH from the brain and its actions to cause the release of other reproductive hormones. In this project we will determine how stress acts in the brain to affect the secretion and actions of GnRH in males and females. Our research will make a major contribution to our knowledge of the way that stress inhibits reproduction in males and females. This information is essential in order to develop specific remedies to overcome reproductive disorders caused by stress and to improve reproductive health in both sexes.Read moreRead less
Genetic And Metabolic Determinants Of Spontaneous Physical Activity
Funder
National Health and Medical Research Council
Funding Amount
$67,828.00
Summary
It could be argued that obesity is the most significant public health problem facing Australians today. Almost one in five adult Australians are obese, making them highly susceptible to diabetes, coronary heart disease, high blood pressure, high blood lipid levels, and some cancers, as well as reduced psychosocial health. There is therefore an urgent need to reduce the prevalence of obesity in our society. Unfortunately, attempts to sustain significant weight loss by dieting and exercise are nea ....It could be argued that obesity is the most significant public health problem facing Australians today. Almost one in five adult Australians are obese, making them highly susceptible to diabetes, coronary heart disease, high blood pressure, high blood lipid levels, and some cancers, as well as reduced psychosocial health. There is therefore an urgent need to reduce the prevalence of obesity in our society. Unfortunately, attempts to sustain significant weight loss by dieting and exercise are nearly always unsuccessful and none of the anti-obesity drugs currently on the market are safe to use long-term. Effective treatments for obesity are only likely to be developed once we understand more about what controls body weight regulation. An inactive lifestyle is clearly a risk factor for obesity. Spontaneous physical activity (or activity associated with daily life, as opposed to formal exercise) can play a major role in determining body weight. Recent work suggests that spontaneous physical activity is influenced not only by our environment but by our biological makeup as well (i.e. genetic and metabolic factors). The aim of this study is to investigate what some of these factors are, and whether they are responsible for altering body weight regulation in animal models of obesity. Specifically we will be looking at whether spontaneous physical activity is influenced by circulating hormones (such as leptin, oestrogen, and pancreatic polypeptide) and a messenger molecule (nitric oxide), and we will also identify genes which influence physical activity in a mouse model of obesity. By examining the genetic and metabolic basis of inactivity in obese rodent models, this project will further our understanding of how energy balance is disturbed in obesity in the hope of developing better therapies to treat obesity in the future.Read moreRead less
Osteoporosis is a major health burden resulting from bone fractures in older men and women due to progressive loss of bone and weakening of the skeleton. No current treatment effectively reverses this bone loss. Using genetic models in mice, we have identified a pathway, involving the nerve signal molecule NPY, that is capable of inducing large (200 - 300%) increases in bone very rapidly (within a few weeks), in the skeleton of adult mice. This proposal is aimed at characterising this new pathwa ....Osteoporosis is a major health burden resulting from bone fractures in older men and women due to progressive loss of bone and weakening of the skeleton. No current treatment effectively reverses this bone loss. Using genetic models in mice, we have identified a pathway, involving the nerve signal molecule NPY, that is capable of inducing large (200 - 300%) increases in bone very rapidly (within a few weeks), in the skeleton of adult mice. This proposal is aimed at characterising this new pathway to assess its potential to provide new treatments for human osteoporosis. This research is important because of the size, rapidity and inducibility of the effect. Moreover, since it originates in the brain, it represents a quite novel mechanism by which the skeleton is potentially maintained and repaired. The experiments contained in the initial sections of the proposal are designed to assess not only the ability of the NPY-pathway to protect against bone loss but also to examine the possibility of repair to a fragile skeleton. The bone loss models chosen for study represent postmenopausal and age-related osteoporosis, two prevalent and increasingly common conditions in the aging world population. The latter section of the proposal seeks to clarify the mechanism by which the increase in bone formation occurs within the bone. Understanding the working of this pathway will be vital in developing future treatment regimens. This proposal investigates a novel, powerful and rapid pathway for repairing weakened skeletons. The knowledge resulting from this proposal has the potential to provide an important contribution to skeletal health and thus aged health worldwide.Read moreRead less