The amyloid beta (Ab) protein is implicated in Alzheimer’s Disease through its ability to impair brain metabolism. We have recently found that Ab can also impair metabolism in other tissues. This project will determine the role of Ab in regulating whole body metabolism and determine whether it is implicated in the development of metabolic diseases such as type 2 diabetes.
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.
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.
Blocking IL-6 Trans-signaling: A Therapeutic Strategy To Prevent Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$540,636.00
Summary
It is well known that blocking the recruitment of specific immune cells namely macrophages to adipose tissue of obese patients will improve their metabolic health. However, to date, a viable drug to do this has remained elusive. We have developed such a drug called sgp130Fc. This project will test the effectiveness of this drug in a pre-clinical setting.
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.
Activation Of HSP72 In Skeletal Muscle As A Therapeutic Target For Obesity
Funder
National Health and Medical Research Council
Funding Amount
$656,033.00
Summary
We recently discovered that activation of a protein, namely Heat Shock Protein 72, can prevent obesity and insulin resistance in mice. We have developed a small molecule activator of this protein which has undergone preliminary human clinical trials. This project will extend upon this initial finding to determine the precise mechanism by which activation of this protein prevents obesity and insulin resistance.
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.
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.
While it is clear that carrying excess body weight can jeopardize your health, and that losing excess weight is good for you, attaining and maintaining a healthy body weight remains an elusive goal for more than 60 % of Australian adults. There are many barriers that make permanent weight loss difficult. One of the main biological barriers to weight loss is that humans aren t designed to diet. Instead, we vehemently conserve body fat whenever food is scarce. This leads to a Famine Reaction that ....While it is clear that carrying excess body weight can jeopardize your health, and that losing excess weight is good for you, attaining and maintaining a healthy body weight remains an elusive goal for more than 60 % of Australian adults. There are many barriers that make permanent weight loss difficult. One of the main biological barriers to weight loss is that humans aren t designed to diet. Instead, we vehemently conserve body fat whenever food is scarce. This leads to a Famine Reaction that contributes to nagging hunger, lethargy, loss of libido, reduced metabolic rate, plateaus, and rebound weight gain in response to weight loss programs of any kind. In a new 3-year project funded by the National Health and Medical Research Council of Australia, molecular scientists Dr Amanda Sainsbury-Salis and Associate Professor Herbert Herzog from the Garvan Institute endeavor to get to the root of the problem. Using cutting-edge molecular, genetic, and metabolic technology, Sainsbury-Salis and Herzog aim to identify the main culprits for the Famine Reaction. They hypothesize that the natural brain molecules neuropeptide Y and the endogenous morphine-like peptide dynorphin act together as major instigators of the Famine Reaction. Therefore they will determine whether mice that are deficient in these molecules can lose more weight in response to dietary restriction than normal mice. Moreover, they will determine whether dual deficiency of neuropeptide Y and dynorphin can not only reduce the voracious appetite that occurs during caloric restriction (eg: dieting), but whether it can also speed up metabolism and promote the loss of body fat. If their hypothesis proves correct, then it s likely that novel pharmaceutical agents that block the effects of neuropeptide Y and dynorphin could dramatically increase the do-ability and long-term effectiveness of lifestyle changes for permanent weight loss.Read moreRead less
Mechanisms Of Weight And Adipose Loss Following Inhibition Of The Renin-angiotensin System
Funder
National Health and Medical Research Council
Funding Amount
$330,722.00
Summary
As an energy homeostasis researcher, with a particular interest in ingestive behaviour, I plan to examine the role the renin-angiotensin system in energy balance and obesity. I will achieve this by spending two years learning new techniques and conducting research in one of the top energy balance labs in the world, headed by Professor Stephen Woods (University of Cincinnati). I will then return to Australia to implement the techniques I have learned and extend this research.