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.
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.
Obesity ensues when calorie intake exceeds energy expended. Hitherto, up-regulating energy expenditure is a relatively unexplored avenue. This project will address 3 facets of energy expenditure (fat, muscle and neural control). Understanding how sex and steroids act in concert to regulate energy expenditure will pave the way towards developing novel anti-obesity agents. This work will delineate mechanisms that underpin gender differences in the regulation of body weight.
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.
How Does Paternal Obesity Influence Offspring Glucose Tolerance?
Funder
National Health and Medical Research Council
Funding Amount
$503,398.00
Summary
Obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. We have shown that normal females mated with obese fathers consuming high fat diet, produce offspring who develop glucose intolerance and impaired insulin secretion. This work will examine the mechanisms underlying this effect in the rat, testing a novel role for environmental factors in the father on disease in offspring that may be relevant to the growing obesity epidemic.
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.
Obesity is caused by an energy imbalance, where energy intake from eating food exceeds energy expended by physical exertion and metabolism. This proposal will provide a fundamental advance in our understanding of how the brain communicates with fat to control energy expenditure and body weight.
Circadian Rhythm Disruption And Metabolic Function
Funder
National Health and Medical Research Council
Funding Amount
$626,018.00
Summary
Shiftwork is an under-researched risk factor for obesity and diabetes. Because shiftwork disrupts hormonal and sleep rhythmicity, eating patterns and light exposure, abnormal rhythmicity may be a causal factor in metabolic disease. Direct evidence for the link is lacking and the underlying mechanisms responsible are unknown. This project aims to understand how shiftwork may lead to diabetes and obesity, knowledge essential for the design and testing of potential interventions.
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.