MECHANISTIC ROLE OF CHOLESTEROL IN NON-ALCOHOLIC STEATOHEPATITIS
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Fatty liver is present in 15-30% of Australians, related to obesity, diabetes and heart attack. Two-thirds of cases reverse easily. The remainder evolve to non-alcoholic steatohepatitis (NASH), liver damage that can lead to cirrhosis and liver failure. This research seeks to find out why some cases of fatty liver lead to NASH, and whether cholesterol that accumulates in the livers of mice with NASH is what causes that damage. If so, we will find new ways to treat NASH by diet or drugs.
Characterising An Important Control Point In Cholesterol Synthesis Beyond HMG-CoA Reductase
Funder
National Health and Medical Research Council
Funding Amount
$480,739.00
Summary
The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol- ....The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol-related diseases.Read moreRead less
The Role Of Phosphatidic Acid In Lipid Storage And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$496,169.00
Summary
The prevalence of obesity and its related disorders has reached an alarming level in Australia and other developed countries. Obesity is characterized by the accumulation of fully-differentiated adipocytes loaded with lipid droplets (LDs). We aim to examine the role of phosphatidic acid in lipid droplet formation and adipocyte differentiation. Results from our proposed studies may offer novel therapeutic strategies against human obesity and type II diabetes.
Targeting The Class IIa Histone Deacetylases In Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Dysfunctional metabolism in skeletal muscle is integral in the development of metabolic diseases, such as obesity and type 2 diabetes. This project will examine proteins that alter the way genes are expressed for their role in dysfunctional metabolism in muscle. This project could uncover new therapies for the treatment of metabolic diseases.
Identification Of The Mechanisms Of Lipotoxicity Within The Bone Marrow Milieu
Funder
National Health and Medical Research Council
Funding Amount
$416,007.00
Summary
Obesity and osteoporosis two major epidemics of our time. Bone and fat communicate with each other in two different ways. A hormonal communication links bone and fat in a positive manner. In contrast, at the local level, increasing levels of marrow fat with aging affect bone quality through the local release of toxic factors. We will identify these factors and will assess the potential reversibility of lipotoxicity in bone, as a new therapeutic approach to osteoporosis in the elderly.
Understanding The Role Of Class IIa Histone Deacetylases In Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$469,779.00
Summary
Dysfunctional metabolism in skeletal muscle is integral in the development of metabolic diseases, such as obesity and type 2 diabetes. This project will examine proteins that alter the way genes are expressed for their role in dysfunctional metabolism in muscle. This project could uncover new therapies for the treatment of metabolic diseases.
Role Of Lysosomal Acid Lipase In Regulating Insulin Secretion
Funder
National Health and Medical Research Council
Funding Amount
$570,928.00
Summary
Type 2 diabetes (T2D) affects 7% of Australians and is a major cause of morbidity and mortality. A failure of insulin secretion contributes to T2D, and this is linked to the inability of insulin producing ?-cells to use lipids appropriately (lipotoxicity). Here we will study the role of a cellular body called the lysosome to regulate ?-cell lipid metabolism and insulin secretion. This work will greatly increase the understanding of ?-cell failure in T2D.
Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s diseas ....Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s disease.Read moreRead less
Role Of Macrophages In Lipotoxic Beta Cell Failure
Funder
National Health and Medical Research Council
Funding Amount
$612,736.00
Summary
Type 2 diabetes (T2D) affects 7% of Australians and is a major cause of morbidity and mortality. A failure of insulin secretion contributes to T2D, and this is linked to the inability of insulin producing ?-cells to use lipids appropriately (lipotoxicity). Here we will study the role of the immune system and how this inhibits insulin secretion in T2D