Sphingosine Kinase: A Target For Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$626,845.00
Summary
Insulin resistance, a characteristic of type 2 diabetes, is linked to abnormal metabolism of lipid (fat) in tissues such as liver and muscle. This project aims to identify a novel pathway which may promote a build up of lipids in liver and therefore leads to the development of type 2 diabetes. This work may provide a basis for understanding and optimizing treatment of insulin resistance by regulating the control of fat metabolism in liver.
The CDP Ethanolamine Pathway: A New Player In Obesity Induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$652,372.00
Summary
Insulin resistance, a characteristic of type 2 diabetes, is linked to abnormal metabolism of lipid (fat) in tissues such as liver and muscle. This project aims to identify a novel pathway which may promote a build up of lipids in muscle and therefore leads to the development of type 2 diabetes. This work may provide a basis for understanding and optimizing treatment of insulin resistance by regulating the control of fat metabolism in muscle.
Understanding The Role Of Sugar Metabolism In Liver Tumour Growth
Funder
National Health and Medical Research Council
Funding Amount
$631,979.00
Summary
Primary liver cancer is a deadly disease with limited chemotherapeutic options. The investigators of this proposal have recently determined that sugar intake (but not fat or complex carbohydrate) is a dominant driver of liver tumour growth in mice. The current proposal will investigate the specific contributions of glucose versus fructose in tumour burden, and determine whether blocking the conversion of sugars to fat in the liver represents a therapeutic strategy to block tumour growth in mice.
Does Periodic Fasting Improve Insulin Sensitivity And Metabolic Health In Humans?
Funder
National Health and Medical Research Council
Funding Amount
$846,891.00
Summary
A large body of evidence for the health benefits and life-extending properties of dietary restriction exists. Recent findings suggest that periods of fasting can have beneficial effects, even without an overall reduction in caloric intake. This proposal will compare periodic fasting with and without weight loss, versus daily caloric restriction on metabolic health outcomes in humans and examine mechanisms that may contribute to this effects.
A physiologist describing metabolic pathways and mechanisms that regulate lipoprotein metabolism in in vitro and in vivo systems. My research uses complex tracer studies and mathematical modelling to identify and quantitate pathways of lipid metabolism in normal and diseased states prior to and following lifestyle and-or pharmacological interventions.
REGULATION OF LIPID METABOLISM IN SKELETAL MUSCLE BY IDOL – A Novel Degrader Of The Very Low Density Lipoprotein Receptor
Funder
National Health and Medical Research Council
Funding Amount
$557,162.00
Summary
More than 1 in 5 Australians are estimated to have increased levels of fats (triglycerides; TGs) in the blood, commonly due to excess dietary intake or genetics. The excess TGs are deposited in skeletal muscle where they can cause insulin resistance, increasing the risk of developing diabetes, the fastest growing chronic condition in Australia. I will examine whether a recently identified protein, IDOL, can reduce accumulation of TGs in skeletal muscle and protect against insulin resistance.
Lifestyle And Pharmacological Regulation Of Lipoprotein Metabolism In The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$504,504.00
Summary
Visceral obesity is an increasing problem in Australia. Elevated blood fat levels are associated with visceral obesity and increased risk for heart disease. Effective management of lipid disorders is important to reduce the risk for heart disease. Fats in the blood originate from dietary sources and from synthesis by the liver. In viscerally obese subjects, the level of blood fats is elevated compared with lean individuals. These abnormalities are partly caused by overproduction of fat in the li ....Visceral obesity is an increasing problem in Australia. Elevated blood fat levels are associated with visceral obesity and increased risk for heart disease. Effective management of lipid disorders is important to reduce the risk for heart disease. Fats in the blood originate from dietary sources and from synthesis by the liver. In viscerally obese subjects, the level of blood fats is elevated compared with lean individuals. These abnormalities are partly caused by overproduction of fat in the liver and impaired clearance of fat from the blood. Two particular proteins, called apolipoprotein A and B-100, are important fat carriers responsible for transporting fat in the blood. Viscerally obese subjects have abnormal levels of these apoproteins and we hypothesised that they are responsible for the impaired movement of fat in the blood. Viscerally obese subjects are insulin resistant and are prone to diabetes. This condition will impair the regulation of apolipoproteins A and B-100. In this research project, we will investigate the effect of a fibrate (a regulator of fat production and breakdown) and ezetimibe (a regulator of dietary cholesterol absorption) on the production and clearance rates of apolipoprotein A and B in a group of obese subjects who are on weight loss program . If our hypothesis is correct, these studies will demonstrate new mechanisms of action of the two drugs that will complements the favourable effect of weight loss in the treatment of elevated blood fats and reduction in risk of heart disease in an important groups of subject in the population.Read moreRead less
I am a cell /whole body integrative biologist determining the cellular and molecular mechanisms that lead to insulin resistance in insulin sensitive tissues such as skeletal muscle, liver and adipose tissue. My work primarily focuses on targeting inflammatory signalling cascades that lead to impaired insulin action, and pathways that enhance energy utilization.
An Integrated Approach To Identify The Molecular Mechanisms Contributing To The Pathogenesis Of Insulin Resistance: Targeting The Liver And Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
The inability of muscle and liver to utilise sugar from the blood is a major problem that contributes to the development of obesity and diabetes. How these problems occur is unknown. The goal of my research is to identify what causes the muscle and liver problem, and whether fixing these problems will reduce obesity and diabetes. Since the number of people with obesity and diabetes is predicted to double over the next decade, we need to understand the cause of these diseases.
Transcriptome Landscape Of Brown/beige Adipogenesis In Humans
Funder
National Health and Medical Research Council
Funding Amount
$393,369.00
Summary
There are three kinds of fat in the body: white, brown and beige. While excess white fat results in obesity, brown fat is associated with leanness and lowers blood glucose levels. Recent animal experiments show that under certain conditions, white fat can be transformed into beige fat, leading to benefits such as weight loss. The current project grant involves examination of human fat cells grown in the laboratory and investigation on the genetics of brown and beige fat.