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This research proposal will identify changes in liver-secreted proteins during the development of fatty liver, and in the transition from fatty liver to the more advanced form of liver disease, non-alcoholic steatohepatitis (NASH). Understanding the differences in protein secretion between NASH patients and patients with normal/fatty liver will provide the opportunity to identify disease biomarkers that could be determined from a blood sample. This will provide a major shift in clinical care.
Altered Protein Secretion Links The Fatty Liver To Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$415,797.00
Summary
The liver secretes proteins to alter metabolism in other tissues of the body. Fatty liver is a major feature of obesity and type 2 diabetes. This project aims to understand how fatty liver changes protein secretion and how this impacts on metabolic processes. The outcomes of this project will be the identification of protein biomarkers of fatty liver and the prediction of insulin resistance development in other tissues of the body.
Protective Mechanisms Of MAP Kinase Phosphatase 5 In Adipose Tissue Fibrosis, Hepatic Steatosis And Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$352,729.00
Summary
Obesity and associated complications such as diabetes, non-alcoholic fatty liver disease and atherosclerosis are a serious health burden. Recently, we found that MKP5, a molecule that restricts intracellular signaling, plays a central role in preventing these diseases. This collaborative project will elucidate how precisely MKP5 acts and explore how this molecule can be targeted for the development of novel therapeutic strategies in prevention and treatment of human metabolic diseases.
The Role Of GAPDH Acetylation And HDAC6 In Liver Metabolism And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$635,428.00
Summary
Type 2 diabetes (T2D) is characterised by persistent elevated blood glucose levels. Altered liver metabolism is a key contributor to elevated blood glucose levels in T2D, through uncontrolled synthesis and release of glucose. This project will examine whether regulation of a metabolic enzyme called GAPDH by a process termed acetylation, contributes to normal liver glucose metabolism. This project will also assess whether altered GAPDH acetylation contributes to hyperglycaemia in T2D.
The Alternate Renin Angiotensin System; A Novel Target For The Prevention And Treatment Of Liver Fibrosis And Portal Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$693,950.00
Summary
Cirrhosis of the liver due to chronic hepatitis and other common liver diseases is now a major cause of illness and death in Australia. This project will examine how a hormone system called the renin angiotensin system contributes to the development of liver damage in these diseases. We will study whether drugs targeting this system can be used to reduce liver scarring and prevent the development of cirrhosis and its complications.