This study aims to elucidate central pathways which can be manipulated to drive the storage of excess energy away from fat and instead directing it into the production of bone mass. Having identified leptin-responsive NPY neurons as important in the control of energy partitioning, we will focus on manipulating these neurons in the hypothalamus using innovative technology to alter body composition. This research has the potential to result in novel treatments for obesity and osteoporosis.
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 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