The Role Of The Central Insulin-NPY Pathway In The Regulation Of Energy Balance
Funder
National Health and Medical Research Council
Funding Amount
$474,975.00
Summary
Insulin is known for its role in the regulation of glucose metabolism in the liver, muscle and fat, however very little is known about the role of insulin in the brain. This project aims to improve our understanding on how insulin regulates energy balance and appetite and identifies the exact neuronal networks involved in the brain and to understand the mechanistic insights into the pathology of obesity, providing the means for the development of more effective and safer therapeutic approaches.
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.
RANKL, A Critical New Player In The Coordination Of Whole Body Energy Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$842,946.00
Summary
Imbalances in food intake and energy expenditure can lead to the development of obesity or anorexia. Conserved mechanisms are in place to coordinate the energy requirements of organs and tissues. The main centre is the brain which receives, processes and sends out information to accommodate the needs of the different tissues. Bone tissue in particular is in need of a lot of energy. Factors produced by bone are therefore critical in the coordination of whole body energy homeostasis.
Can Blockade Of Leptin Action In The Brain Reduce Blood Pressure In Obese Mice?
Funder
National Health and Medical Research Council
Funding Amount
$653,049.00
Summary
The aim of these studies is to determine if high leptin levels in obese mammals activate the sympathetic nervous system (SNS), and thereby contribute to pathologically high blood pressure, increased heart rate and diabetes. If so, it may be possible to develop novel therapeutics to acutely improve a patient's metabolic condition, by blocking leptin action. The obese are already insensitive to the anorectic actions of leptin, so blocking leptin would likely have no deleterious consequences.
Identification Of Novel Pathways Controlling Food Intake And Energy Balance
Funder
National Health and Medical Research Council
Funding Amount
$751,006.00
Summary
Obesity-associated diseases are leading causes of death and are expected to increase as the obesity epidemic worsens. Because of the limited efficacy and/or safety concerns of currently available anti-obesity drugs, it is important to identify new drug targets. Investigating the cause of obesity and excessive food intake in natural occurring models like Prader Willi Syndrome (PWS) has the potential to shed new light on the complex regulation of this process and might open up new treatment option ....Obesity-associated diseases are leading causes of death and are expected to increase as the obesity epidemic worsens. Because of the limited efficacy and/or safety concerns of currently available anti-obesity drugs, it is important to identify new drug targets. Investigating the cause of obesity and excessive food intake in natural occurring models like Prader Willi Syndrome (PWS) has the potential to shed new light on the complex regulation of this process and might open up new treatment option for PWS as well as general obese patients.Read moreRead less
Investigation Of The Role Of The Peripheral Neuropeptide Y System In Energy Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$798,760.00
Summary
Obesity-associated diseases are leading causes of death and are expected to increase as the obesity epidemic worsens. Because of the limited efficacy and/or safety concerns of currently available anti-obesity drugs, it is important to identify new drug targets, preferably outside the brain. The results from this study will help to identify agents for obesity that reduce body weight and fat mass without the safety concerns of agents that act on the central nervous system.
Control Of Insulin Secretion By Y1 Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$675,582.00
Summary
Diabetes is the most common metabolic disease worldwide. Impaired insulin secretion and beta cell function is one of its major causes. We have recently discovered a key signaling pathway that we believe hold the secret to inhibiting insulin secretion in beta cells and blocking it leads to significant insulin release. This proposal focuses on this pathway and its regulation using innovative and unique tools. This will provide a novel treatment option for diabetes as well as islet transplantation.
NPY Coordination Of Energy Balance And Physical Activity
Funder
National Health and Medical Research Council
Funding Amount
$844,596.00
Summary
Anorexia nervosa (AN) is an eating disorder characterized by behavioral alterations, restrictive eating leading to extremely low body weight. AN is also associated with a paradoxical hyperactivity representing a failure of the brain to adjust activity to energy status. Here we aim to investigate the role of the Neuropeptide Y (NPY), a known regulator of homeostatic control and activity in the development of hyperactivity in AN, thus help to identify NPY-targeted therapeutics for AN treatment.
Sweet taste is generally associated with calorie rich diet. In the brain this information is used to adjust the amount of food that is eaten and how hungry one feels. Disrupting this balance by supplementing food with artificial sweeteners, which have no caloric content, represents a challenge for the brain. However, specific neuronal pathways are in place to correct this imbalance of calorie to taste and we are interested to identify the major component of these pathways.
Identifying Brain Pathways Responsible For Stress Induced Obesity
Funder
National Health and Medical Research Council
Funding Amount
$895,663.00
Summary
Obesity-associated diseases are leading causes of death and are expected to increase as the obesity epidemic worsens. New evidence also shows that stress, an ever-increasing factor of life, can when combined with high caloric food lead and accelerate the development of obesity. The results from this study will help to identify new agents that may help reduce body weight and fat mass particular under conditions of increased stress.