The Role Of The Adiponectin Receptors In Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$393,159.00
Summary
Advanced liver scarring (fibrosis) contributes to the death of 1500 Australians annually. Two-thirds of our community is overweight or obese, and this worsens liver disease. A protein secreted by fat, adiponectin, may be important as it acts on liver cells to promote fibrosis. To understand adiponectins role, we will use mice null for adiponectin receptor genes and study its action on liver cells. This study will improve our understanding of liver scarring biology and patient treatments.
Molecular Characterisation Of Adiponectin Receptors: Implications For Adiponectin Action And Resistance
Funder
National Health and Medical Research Council
Funding Amount
$95,137.00
Summary
Adiponectin is a hormone secreted by fat cells with anti-inflammatory, anti-atherogenic and insulin sensitising properties. Adiponectin levels and actions are compromised in obesity and type 2 diabetes. Adponectin mediates its effects via two receptors but the mechanisms are poorly understood. This proposal aims to define the underlying mechanisms with the ultimate goal of identifying novel therapeutic strategies to improve adiponectin's actions.
Characterisation Of The Adiponectin Receptors - AdipoR1 And AdipoR2
Funder
National Health and Medical Research Council
Funding Amount
$445,158.00
Summary
The increasing incidence of cardiometabolic disease highlights an unmet need for novel therapeutic approaches. Greater understanding of the detail governing cardiometabolic function is required to provide a foundation to construct effective strategies. We will characterise 2 novel receptors that are important in the regulation and maintenance of cardiometabolic systems, seeking to identify strategies to enhance receptor, improve cardiometabolic function and reduce disease burden.
Adiponectin And Cholesterol: A Driving Force In NASH Immunopathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$436,017.00
Summary
This project examined the role of dietary cholesterol in the pathogenesis of fatty liver disease in a rodent model. We have been able to demonstrate that diets high in cholesterol lead to the development of inflammatory foci in the liver, elevations in the amount of hepatic ceramides (a lipid byproduct) and then leads to the activation of inflammatory molecular pathwways that lead to liver fibrosis. The latter results in end stage liver disease, and in some to the development of liver cancer.
Overweight individuals have an increased risk for developing liver cancer. This may be due to the reduced production of the fat-derived hormone adiponectin. Reduced levels of adiponectin are associated with increased inflammation and liver disease. Using mice not expressing adiponectin we will test its importance in liver cancer growth. The proposed research will provide a better understanding of the factors that promote liver cancer formation.
Adiponectin: Key Factors Determining Its Metabolic Actions And Influences On Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$604,793.00
Summary
Diabetes and obesity are growing at alarming rates due to poor lifestyle and other factors. Adiponectin is a complex molecule secreted by fat tissue that may help to burn fat in other tissues such as muscle and liver. We investigate what are the main determinants of adiponectin action and how these might counteract defective insulin action caused by excessive fat intake. This promises to provide new therapeutic targets to lessen the metabolic derangement associated with diabetes and obesity
Molecular Characteristation Of The Adiponectin Receptors, AdipoR1 And AdipoR2: Identifying Strategies To Enhance Adiponectin Sensitivity And Reduce Cardiometabolic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$334,634.00
Summary
Obesity and Type 2 diabetes (T2D) increase risk of cardiovascular disease (CVD), a leading cause of death in Australia. New drugs are required to reduce the health risks and financial burden of these diseases. Targeting hormone receptors to reduce fat storage in liver and skeletal muscle in obesity may improve insulin sensitivity and reduce blood sugar levels and therefore reduce CVD risk. This research will study how these receptors function in order to develop new drugs to reduce CVD risk.
Novel Approaches To The Targeting Of GPCRs Towards Improved Treatment Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
The focus of these studies are two important types of brain proteins that have been implicated in various symptoms associated with schizophrenia. The aim is to exploit two emerging paradigms of drug action at these brain proteins that will allow us to target them in a more selective manner. In particular, these studies will provide a starting point for safer, more effective treatments for schizophrenia.