The Metabolic Effects Of Oestrogens And SERMs: Regulatory Interactions With The GH-IGF-system In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$379,142.00
Summary
This project extends work aimed at understanding how GH and sex hormones work together to optimise physical health in women and men. It addresses the benefits and safety of oestrogen compounds in relation to their effects on body fat and muscle (body composition). Oestrogen compounds are among the most widely used medicines and include tradition oestrogens (female hormone) and synthetic oestrogens called SERMs. Oestrogens are used in young women as oral contraception and in the postmenopause for ....This project extends work aimed at understanding how GH and sex hormones work together to optimise physical health in women and men. It addresses the benefits and safety of oestrogen compounds in relation to their effects on body fat and muscle (body composition). Oestrogen compounds are among the most widely used medicines and include tradition oestrogens (female hormone) and synthetic oestrogens called SERMs. Oestrogens are used in young women as oral contraception and in the postmenopause for replacement therapy. Body composition is an important determinant of fitness and health. Obesity reduces fitness and increases the risk of diabetes and heart attacks while muscle loss causes weakness and frailty. GH is a major regulator of body composition; it acts by breaking down fat and building muscle mass. We discovered that oestrogens, when taken as a tablet interferes with the action of GH and causes detrimental changes in body composition. On the positive side, we have exploited the GH blocking action to treat acromegaly. This is a debilitating disease of excessive GH production from a pituitary tumour and for which available drug treatments are very expensive and require injection. The effects of SERMs on body composition are unknown. SERMs are interesting compounds because they act like oestrogens in some but as oestrogen blockers in other tissues. These are widely used in the treatment of breast cancer and osteoporosis. The extent to which they interfere with the action of GH has not been studied. They may exert additional effects because they act on the pituitary gland to reduce the secretion of GH. They may also prove to be effective in acromegaly which could extend their usefulness to men. In summary, the work will provide important information on the long-term benefits of SERMs in patient groups that tend to be frail. It may also prove to be a simple and inexpensive treatment for acromegaly.Read moreRead less
Improving Weight Loss Outcomes By Minimizing Adaptive Responses To Energy Restriction
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
While losing excess weight reduces the risk of lifestyle diseases such as diabetes, current weight loss strategies are ineffective for most, in part because the body mounts a ‘famine reaction’ that increases hunger, decreases metabolic rate and may also cause loss of muscle and bone mass. This research aims to determine the effects of the famine reaction on body composition, as well as to identify new ways to block the famine reaction with food, thereby enabling more people to attain and maintai ....While losing excess weight reduces the risk of lifestyle diseases such as diabetes, current weight loss strategies are ineffective for most, in part because the body mounts a ‘famine reaction’ that increases hunger, decreases metabolic rate and may also cause loss of muscle and bone mass. This research aims to determine the effects of the famine reaction on body composition, as well as to identify new ways to block the famine reaction with food, thereby enabling more people to attain and maintain a healthy body weight and composition.Read moreRead less
Unveiling The Origin Of Munc18-1 And Alpha-synuclein Co-aggregation At Nanoscale
Funder
National Health and Medical Research Council
Funding Amount
$620,005.00
Summary
Our recent work on Munc18-1 mutations leading to a severe form of human early infantile epileptic encephalopathy (EIEE) led us to uncover a critical role for Munc18-1 in controlling the formation of toxic protein aggregates containing ?-Synuclein. Targeting the Munc18-1 ?-Synuclein interaction may have therapeutic values not only for EIEE but also for other neurological diseases characterised by protein aggregations.
Health Coaching Intervention To Prevent Excessive Gestational Weight Gain
Funder
National Health and Medical Research Council
Funding Amount
$98,507.00
Summary
Excessive weight gain in pregnancy places women at a greater risk for the development of overweight and obesity. This study responds to the urgent need to design effective interventions to prevent excessive weight gain in pregnancy. A health coaching intervention has been designed to address this need, and its effectiveness will be evaluated in a randomised controlled trial with first time pregnant women.
A Randomised Controlled Trial To Prevent Primigravid Excessive Gestational Weight Gain And Postpartum Weight Retention
Funder
National Health and Medical Research Council
Funding Amount
$505,412.00
Summary
Excessive weight gain in pregnancy and weight retention 12 months post birth place women at a greater risk for the development of overweight and obesity. This study responds to the urgent need to design effective interventions to prevent excessive weight gain in pregnancy and postpartum weight retention. A health coaching intervention has been designed to address this urgent need, and its effectiveness will be evaluated in a randomised controlled trial with first time pregnant women.
Long-term Metabolic Effects Of Stress And Antidepressants: A Novel Translational Animal Paradigm Of Drug-induced Obesity
Funder
National Health and Medical Research Council
Funding Amount
$518,231.00
Summary
Do antidepressants contribute to Australia's obesity epidemic? Millions of Australians are treated with antidepressants, which often causes weight gain. Our work shows that even brief exposure to antidepressants exacerbate body weight gain following exposure to chronic stress. This new knowledge represents a significant shift in the understanding of antidepressant-related weight gain. In this project we will study the mechanisms involved in long-term weight gain after exposure to stress and anti ....Do antidepressants contribute to Australia's obesity epidemic? Millions of Australians are treated with antidepressants, which often causes weight gain. Our work shows that even brief exposure to antidepressants exacerbate body weight gain following exposure to chronic stress. This new knowledge represents a significant shift in the understanding of antidepressant-related weight gain. In this project we will study the mechanisms involved in long-term weight gain after exposure to stress and antidepressants in an obesogenic environment.Read moreRead less
Heart failure is a severely debilitating condition with a poor prognosis. It is characterized by retention of fluid and high nervous activity especially to the kidneys and the heart. Even with the best current treatment available, patients with heart failure still suffer from abnormally high nerve activity to the further detriment of this condition. The successful completion of this project will provide considerable insight into the role of the brain in the elevated nerve activity in heart failu ....Heart failure is a severely debilitating condition with a poor prognosis. It is characterized by retention of fluid and high nervous activity especially to the kidneys and the heart. Even with the best current treatment available, patients with heart failure still suffer from abnormally high nerve activity to the further detriment of this condition. The successful completion of this project will provide considerable insight into the role of the brain in the elevated nerve activity in heart failure. It will also provide us with a significant understanding of the role in reflex sympathetic nerve regulation of an important brain region known as the hypothalamic paraventricular nucleus (PVN). Our findings will help us understand the nature of the neurotransmitters contributing to the reflex nerve regulation and the specific neurons within the PVN involved. This knowledge could help us to identify novel potential therapeutic targets within the brain to alleviate the problems observed in heart failure.Read moreRead less
Anabolic Steroids: The Emergent Public Health Threat Facing Australian Boys And Men
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Steroid use is a growing public health threat with devastating health consequences for boys and men. In response, we will investigate i) how steroid use develops among high-school boys, and ii) the experience of steroid use among current steroid users. Findings will inform models of how steroid use develops, help prevention and treatment efforts, and help to change the thinness- and female-centric criteria for diagnosing eating disorders to better accommodate males and muscularity.
Several natural chemicals in the brain and gut that regulate food intake and body weight have been identified. Their actions in regulating these processes are achieved through a complex yet little understood interaction with various molecules and receptors which leads to a cascade of reactions in the central nervous system. The aim if this PhD project is to elucidate the mechanisms of these interacting molecules to develop novel and effective leads for the prevention and treatment of obesity.