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Central Neural Mechanisms Underlying The Effect Of Endocannabinoids On Body Weight
Funder
National Health and Medical Research Council
Funding Amount
$377,793.00
Summary
Obesity and its associated pathologies of cardiovascular and respiratory disease, stroke, predisposition to some cancers and infertility in women no longer needs to be justified as a major health issue in modern societies. In fact it is quickly becoming recognised as the major threat to world health. Recently, the anecdotal evidence for increased food intake, particularly the craving of high carbohydrate, high sugar foods, associated with the use of marijuana has been put into a therapeutic cont ....Obesity and its associated pathologies of cardiovascular and respiratory disease, stroke, predisposition to some cancers and infertility in women no longer needs to be justified as a major health issue in modern societies. In fact it is quickly becoming recognised as the major threat to world health. Recently, the anecdotal evidence for increased food intake, particularly the craving of high carbohydrate, high sugar foods, associated with the use of marijuana has been put into a therapeutic context. Specifically a cannabinoid receptor antagonist, rimonabant (currently undergoing trials as Accomplia) has become a central player in the race for an obesity therapy because of its effects in blocking the brain receptors that would normally respond to cannabinoid like compounds in the brain that tend to increase food intake. Despite the trials that are underway in Europe and the USA many of the central actions of the naturally occurring cannabinoids in the brain, the so-called endocannabinoids are very poorly understood. This series of experiments utilizing the best technologies available will address basic questions relating to the brain pathways involved and even the extent to which weight loss associated with the administration of these drugs to rats and presumably humans is dependent on the reduction of food intake or the burning of energy in a process called thermogenesis. These are essential pieces of information if this type of compound is to be considered as a serious contender in the search for an obesity therapyRead moreRead less
CNS Peptides Involved In The Control Of Thermogenesis And Body Weight
Funder
National Health and Medical Research Council
Funding Amount
$405,750.00
Summary
There is currently an obesity epidemic in all industrialised countries which has an associated impact on cardiovascular disease and associated pathologies such as type 2 diabetes. Current therapeutic strategies have focussed on reducing food intake but, as evidenced by the continuation of this epidemic, these have had limited success. An alternative approach, which is the subject of this project, is to determine and modify the central mediators controlling energy expenditure. We will bring a raf ....There is currently an obesity epidemic in all industrialised countries which has an associated impact on cardiovascular disease and associated pathologies such as type 2 diabetes. Current therapeutic strategies have focussed on reducing food intake but, as evidenced by the continuation of this epidemic, these have had limited success. An alternative approach, which is the subject of this project, is to determine and modify the central mediators controlling energy expenditure. We will bring a raft of new technologies to examine this question and potentially identify new avenues for therapeutic intervention in obesity.Read moreRead less
DIET-INDUCED OBESITY ALTERS THE CENTRAL ACTIONS OF GHRELIN
Funder
National Health and Medical Research Council
Funding Amount
$38,599.00
Summary
Ghrelin is a hormone that primarily targets the brain to increase food intake and body weight. It has evolved to prevent starvation during periods of negative energy balance by promoting energy intake and storage. We have identified central ghrelin resistance in diet-induced obesity (DIO) as a novel disturbed neuroendocrine system that restricts excessive food intake. Therefore, a novel approach to treat DIO is to exploit or enhance these intrinsic mechanisms that restrict the development of obe ....Ghrelin is a hormone that primarily targets the brain to increase food intake and body weight. It has evolved to prevent starvation during periods of negative energy balance by promoting energy intake and storage. We have identified central ghrelin resistance in diet-induced obesity (DIO) as a novel disturbed neuroendocrine system that restricts excessive food intake. Therefore, a novel approach to treat DIO is to exploit or enhance these intrinsic mechanisms that restrict the development of obesity.Read moreRead less
The Role Of Brain Inflammation In Leptin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$730,123.00
Summary
Melanocortin neurons control body weight and are regulated by leptin. In obesity leptin cannot regulate the melanocortin system. We will test if leptin action on melanocortin neurons is limited by increased expression of suppressor of cytokine signalling 3 (SOCS3) in obese mice. As an alternative we will test if there are changes in the blood brain barrier, or an increased density of support and immune cells around melanocortin neurons of obese mice that might restrict inputs to these neurons.
Targeting Central Inflammation To Combat Obesity And Obesity-related Cognitive Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
The current obesity epidemic means many of us will suffer from overweight or obesity for at least some of our lives. My findings show obesity can cause inflammation throughout the brain including in regions related to learning and memory. Here I hypothesize that obesity induces long-term changes in the brain’s immune cells, that this can explain why we see susceptibility to cognitive decline in obese individuals, and that we can reverse these negative effects by targeting these immune cells.
Ghrelin Receptor Signaling In The Brain Links Hunger To Mood And Motivation
Funder
National Health and Medical Research Council
Funding Amount
$721,909.00
Summary
Cells in the brain that respond to hunger may also promote obsessive compulsive behaviours often associated with mental illness, such as anorexia nervosa. This grant examines how the signals from the body inform the brain of hunger. Specially we examine if overactivity of hunger cells, in the absence of appropriate food intake can increase behaviours associated with mental illness.
Does Obesity Have The Characteristics Of Addiction?
Funder
National Health and Medical Research Council
Funding Amount
$430,832.00
Summary
The number of overweight or obese people in Australia has increased dramatically in recent years, increasing disease risk. The brain responds to palatable food in ways similar to the response to drugs of addiction, and this may explain why people find it hard to resist palatable food. Our work will explore whether obesity in rats has the characteristics of addiction by examining bingeing, craving, withdrawal and brain circuits in animals chronically exposed to palatable food.
Obesity: The Role Of Neuropeptide Y, Melanocortin And Serotonin Systems In Development And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
This project is about the study of central regulation of energy balance contributing to protection 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 financially. Development of human obesity and its related metabolic disorders is a long term process generally develops over a long period and event ....This project is about the study of central regulation of energy balance contributing to protection 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 financially. Development of human obesity and its related metabolic disorders is a long term process 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, studies on both humans and experimental animals have revealed that not all individuals become obese on a high-energy diet; thus, individual susceptibility is an important phenomenon allowing us to search for the genes contributing to the individuals' susceptibility or resistance to diet-induced obesity and to identify for effective targets for both prevention and treatment of obesity. Using the animal models developed in our laboratory, the proposed research aims to demonstrate the differences in the central regulation between the mice resistant or susceptible to the development of chronic high-energy diet-induced obesity. Outcomes of this project will provide us with: 1) better targets for the prevention of diet-induced obesity; (2) more effective treatments for the late stage of obesity and its related metabolic disorders; and (3) a better understanding of the individual susceptibility to diet-induced obesity.Read moreRead less
This Project will produce the first map of the brain mechanisms that motivate unhealthy food choices in obesity. This outcome can inform the development of novel treatment approaches for obesity that modify the preference for high-calorie, unhealthy foods by changing the neural bases of such preferences.
Post-stroke Hyperglycaemia – Treatment With Exenatide In Acute Ischaemic Stroke (TEXAIS) Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,266,149.00
Summary
Raised blood glucose levels (hyperglycaemia) after a stroke is common. It reduces the efficacy of stroke treatments and results in worse outcomes. Insulin is not useful as a treatment for this as it causes frequent hypoglycaemia and does not improve clinical outcomes. Exenatide is a common diabetes drug that is simple to use and lowers blood glucose without hypoglycaemia. It will be tested in the Treatment with Exenatide in Acute Ischaemic Stroke (TEXAIS) trial.