Gene Variants In Adiponectin And Its Receptors As Risk Factors For Metabolic And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$534,107.00
Summary
Obesity has a major impact on the development of metabolic syndrome (MetS), type 2 diabetes (T2D), and cardiovascular disease (CVD). It is important to identify the molecular links between obesity and these conditions. Adiponectin, an adipocyte-specific hormone, is a likely molecular candidate because of its pleiotropic metabolic actions. We will investigate the role of adiponectin, the variants within its gene ADIPOQ, and that of its two receptors, in the development of MetS, T2D, and CVD.
Short Term Effects Of Overfeeding On Metabolic Risk In Humans
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Obesity is associated with increased risk of diabetes, heart disease and cancer. Obesity prevalence is rapidly increasing and consitutes one of the greatest threats to human health. The aim of this study is to determine mechanism-s underlying the close relationship between obesity and insulin resistance by inducing experimental weight gain in humans with and without a genetic predisposition to diabetes. This project will help identify new candidates for anti-diabetes drugs.
Molecular Characterisation Of Adiponectin Receptors: Implications For Adiponectin Action And Resistance
Funder
National Health and Medical Research Council
Funding Amount
$95,137.00
Summary
Adiponectin is a hormone secreted by fat cells with anti-inflammatory, anti-atherogenic and insulin sensitising properties. Adiponectin levels and actions are compromised in obesity and type 2 diabetes. Adponectin mediates its effects via two receptors but the mechanisms are poorly understood. This proposal aims to define the underlying mechanisms with the ultimate goal of identifying novel therapeutic strategies to improve adiponectin's actions.
Adiponectin: Key Factors Determining Its Metabolic Actions And Influences On Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$604,793.00
Summary
Diabetes and obesity are growing at alarming rates due to poor lifestyle and other factors. Adiponectin is a complex molecule secreted by fat tissue that may help to burn fat in other tissues such as muscle and liver. We investigate what are the main determinants of adiponectin action and how these might counteract defective insulin action caused by excessive fat intake. This promises to provide new therapeutic targets to lessen the metabolic derangement associated with diabetes and obesity
The Effect Of Ghrelin, Leptin And Orexins On The Function Of Pituitary Somatotropes In Rat, Mouse And Human.
Funder
National Health and Medical Research Council
Funding Amount
$447,000.00
Summary
Malnutrition such as obesity or wasting syndrome is accompanied by GH deficiency. Three newly discovered metabolic regulatory hormones, leptin from fat tissue, ghrelin from stomach and orexins from hypothalamus, play important roles in regulating appetite, energy expenditure, and adiposity. Receptors for three metabolic regulatory hormones are all present in pituitary GH secreting cells (somatotropes) and accumulated laboratory data indicate a modification of GH secretion by three hormones. Cont ....Malnutrition such as obesity or wasting syndrome is accompanied by GH deficiency. Three newly discovered metabolic regulatory hormones, leptin from fat tissue, ghrelin from stomach and orexins from hypothalamus, play important roles in regulating appetite, energy expenditure, and adiposity. Receptors for three metabolic regulatory hormones are all present in pituitary GH secreting cells (somatotropes) and accumulated laboratory data indicate a modification of GH secretion by three hormones. Contradictory results have however been reported. Mechanisms of action of these three hormones are not clear and the interrelationship between metabolic regulatory hormones and intrinsic GH regulatory system is unknown. We propose to clarify this issue by investigating the effect of in vivo treatment of mice and in vitro treatment of cultured pituitary cells with leptin, ghrelin, and orexins. GH secretion, GH and GH-regulatory hormones' receptor synthesis in pituitary somatotropes will be measured. We will also use GH-GFP transgenic mice, in which somatotropes are specifically marked with green fluorescent signal, to study morphological change of somatotropes in mouse pituitary glands after in vivo treatment. By completing this project, we will be able (1) to clarify the physiological role of metabolic regulatory hormones in control of GH levels and (2) to clarify the pathological role of metabolic regulatory hormones in GH deficiency occurred in malnutritional conditions.Read moreRead less
Investigation Of Transgenic Mouse Models Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$412,200.00
Summary
Type 2 diabetes is a common condition characterised by high blood glucose, that afflicts 700,000 Australians. It causes blindness, kidney failure and an increased risk of heart attack and stroke. despite intensive study over many years, the reasons for the elevated blood glucose in this condition are not fully understood. Several abnormalities can contribute to the high glucose and different researchers have proposed different defects as the initial cause. It has proven difficult to unravel the ....Type 2 diabetes is a common condition characterised by high blood glucose, that afflicts 700,000 Australians. It causes blindness, kidney failure and an increased risk of heart attack and stroke. despite intensive study over many years, the reasons for the elevated blood glucose in this condition are not fully understood. Several abnormalities can contribute to the high glucose and different researchers have proposed different defects as the initial cause. It has proven difficult to unravel the sequence of events in the evolution of the syndrome because high glucose can cause insulin resistance and a defect in insulin secretion, both of which can lead to high blood glucose. One approach to study the consequences of specific defects is to genetically engineer them. The aims of this project are to: 1. make a mouse with reduced ability to store glucose in muscle. 2. test the metabolic consequences of a defect in the manufacture of glycogen (starch) in muscle. 3. study the effects of combining a defect in glucose storage with one that results in an oversupply of glucose. 4. study the effects on a mouse with a genetic predisposition for failure of beta cells (insulin making cells) of a defect in muscle glucose storage and over production of glucose. A successful completion of this grant will greatly enhance our understanding of how blood glucose is increased in Type 2 diabetes.Read moreRead less
We have found that leptin, a new hormone produced by fat cells which regulates appetite and metabolism, is a powerful inhibitor of osteoclast formation. Osteoclasts are large cells present in bone which are responsible for bone resorption and therefore these cells contribute to common bone conditions such as osteoporosis, Paget's disease and bone cancer. Osteoporosis causes a great deal of pain and disability and it alone costs the Australian taxpayers more than $400 million per year. Persons wh ....We have found that leptin, a new hormone produced by fat cells which regulates appetite and metabolism, is a powerful inhibitor of osteoclast formation. Osteoclasts are large cells present in bone which are responsible for bone resorption and therefore these cells contribute to common bone conditions such as osteoporosis, Paget's disease and bone cancer. Osteoporosis causes a great deal of pain and disability and it alone costs the Australian taxpayers more than $400 million per year. Persons who are overweight tend to have higher circulating blood levels of leptin and also tend to have denser bones, which suggests that there might be a relationship between blood leptin and bone density or strength. Furthermore, leptin is produced in the bone marrow which is where osteoclasts are produced. Osteoclasts are formed from white blood cells which are present in the bone marrow and the blood. Very recent discoveries have identified a family of new factors which play a key role in the formation of osteoclasts. One of these factors has been called osteoprotegerin and is an inhibitor of osteoclast formation. Mutant mice lacking osteoprotegerin have greatly increased numbers of osteoclasts and severe osteoporosis whereas mutants with too much osteoprotegerin have bones which are much denser than normal. The availability of these factors now allows the generation of human osteoclasts in the laboratory which enables the further study of how the process is regulated. We have found that leptin increases the amount of osteoprotegerin produced by white blood cells and we believe that this is the major way that leptin inhibits osteoclast generation. In this project, we intend to further investigate how and why leptin is able to influence the generation and function of osteoclasts as leptin may be a suitable treatment for osteoporosis and other bone diseases.Read moreRead less