Impact Of Advanced Glycation On Anti-atherogenic Properties Of High Density Lipoprotein
Funder
National Health and Medical Research Council
Funding Amount
$372,471.00
Summary
Type 2 diabetes is a rapidly growing medical problem in Australia and around the world. Diabetes affects human health through its complications and the cardiovascular complications are a cause for major concern. One of the complications is the effect on plasma lipids: it makes cholesterol carrying particles to accumulate in the blood vessels, causing atherosclerosis. We intend to investigate how diabetes modify these particles making them atherogenic.
The Differential Innervation Of Fat - Potential To Target Visceral Adiposity
Funder
National Health and Medical Research Council
Funding Amount
$486,818.00
Summary
Levels of abdominal fat are closely correlated with metabolic syndrome. We propose experiments to identify unique characteristics (neurotransmitters or receptors) of neurons deep in the brain that project specifically to this type of fat or other less harmful subcutaneous fat. We can then test the functional significance of these unique elements in animal experimets involving gene knockdown or pharmacological approaches to modify their function and test the effect on fat distribution
Improving Successful Long-term Weight Loss By Deactivating The Human Famine Reaction
Funder
National Health and Medical Research Council
Funding Amount
$799,102.00
Summary
There are more than 7 million overweight or obese adults in Australia. With conventional methods of weight loss, only 5% of these people will be able to achieve permanent weight reduction of any significance to health outcomes. This project aims to develop more effective and permanent methods of weight management through comparing effectiveness of continuous versus intermittent dieting; and determining what metabolic, hormonal and behavioural factors predict weight regain.
The Role Of Circadian Rhythm Genes In The Regulation Of Energy Balance And Substrate Metabolism In Muscle And Liver
Funder
National Health and Medical Research Council
Funding Amount
$349,263.00
Summary
Obesity is increasing at an alarming rate worldwide and as the standard of living increases in developing countries such as India and China, the incidence of obesity and its related diseases of diabetes, cardiovascular disease and cancer will become the major health problem of the 21st century. The epidemic of obesity appears to be due to a complex interaction between genetic background and changes in the environment such as reduced physical activity and increased availability and consumption of ....Obesity is increasing at an alarming rate worldwide and as the standard of living increases in developing countries such as India and China, the incidence of obesity and its related diseases of diabetes, cardiovascular disease and cancer will become the major health problem of the 21st century. The epidemic of obesity appears to be due to a complex interaction between genetic background and changes in the environment such as reduced physical activity and increased availability and consumption of high energy food. The accumulation of excess body fat in most individuals is not a precipitous event that occurs over a few days or weeks. Obesity actually occurs insidiously over a period years and is essentially the cumulative result of small differences in daily energy balance. In humans and animals energy balance is subject to diurnal or day-night variations in body temperature, feeding behaviour and physical activity (sleep-wake cycles). Recent research has determined that all tissues in the body have the same genes that regulate circadian (daily) rhythms in the brain. It has also become clear that the expression of these gene cycles over 24 hours in muscle liver and fat tissue the same way that they do in the brain. What is not understood is the extent to which these circadian genes control energy metabolism pathways such as glucose and fat utilisation and storage in liver and muscle. The aim of this grant is to test the effects of changing diet, feeding times and circulating hormones on metabolism and gene expression in muscle and liver to determine the extent to which circadian rhythm genes regulate the normal diurnal metabolism of glucose and fat and whether dysregulation of these systems contributes to metabolic disease.Read moreRead less
The Physiology Of Brown Adipose Tissue In Adult Humans
Funder
National Health and Medical Research Council
Funding Amount
$620,026.00
Summary
Brown fat, unlike ordinary fat generates heat by burning calories to maintain body temperature. Originally thought to disappear after birth, recent research including our own have shown that brown fat exists in adult humans in varying amounts. Our aim is to find ways of turning on people�s brown fat allowing them to lose weight by burning more calories.
Function Of Sulfotransferase SULT4A1 - Transcriptional And Post-transcriptional Regulation
Funder
National Health and Medical Research Council
Funding Amount
$302,063.00
Summary
Our understanding of how important proteins work is critical to devising modern approaches for disease treatment. This project looks specifically at a protein sulfotransferase 4A1 linked with schizophrenia, and may be involved in other neuronal disorders. The plan is to characterise how the protein functions and what might be the implications of abnormal regulation. Through a series of intricate experiments, the molecular and cellular properties of the protein will be more clearly defined.
Novel Metabolic Actions Of HDL With Potential Therapeutic Implications For Type 2 Diabetes And The Metabolic Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$349,683.00
Summary
There are currently in excess of 170 million patients diagnosed with type 2 (late onset) diabetes in the world and this figure is expected to double by 2030. Almost one in four Australians 25 years and over has either diabetes or a condition of impaired glucose metabolism. These conditions pose significant problems in terms of both individual suffering and economic burden. Poor diet, sedentary lifestyles with resultant weight gain and increased obesity rates underlie the escalating prevalence of ....There are currently in excess of 170 million patients diagnosed with type 2 (late onset) diabetes in the world and this figure is expected to double by 2030. Almost one in four Australians 25 years and over has either diabetes or a condition of impaired glucose metabolism. These conditions pose significant problems in terms of both individual suffering and economic burden. Poor diet, sedentary lifestyles with resultant weight gain and increased obesity rates underlie the escalating prevalence of type 2 diabetes. Our proposal investigates a novel approach to treat these conditions. We have identified an important link between HDL (good) cholesterol and glucose and fat metabolism in human muscle cells. We have shown that HDL increases glucose uptake into muscle cells. This process would be expected to remove glucose from blood vessels where it causes damage which ultimately contributes to heart attack and stroke. Furthermore, we have shown that HDL increases the amount of fat the body uses. HDL may therefore not only remove damaging fat from blood vessels, but also help to reduce body weight. Our study seeks to determine the relevance of these mechanisms in both healthy individuals and patients with type 2 diabetes. At the conclusion of this grant we expect to understand whether HDL raising strategies may be a an effective new therapy for type 2 diabetes. Specifically, we will understand: 1. how HDL exerts its beneficial effects and 2. whether acute and chronic HDL elevation using drugs improves glucose and fat metabolism in humans.Read moreRead less
Functional Effects Of Polymorphic Variation Of The Aromatase (CYP19) Gene On Enzyme Activity:relationship To Disease
Funder
National Health and Medical Research Council
Funding Amount
$237,708.00
Summary
After menopause, oestrogen synthesis changes from an ovarian to an adipose source by concersion of androgens to estrogens, a process catalyzed by aromatase, the product of the CYP19 gene. We will generate mutants of the CYP19 gene that we have previously found in humans by site-directed mutagenesis and observe the effects of these mutants on aromatase function. This research will help with diagnosis and treatment of breast and other cancers and osteoporosis in humans .