Obesity is becoming more common in Australian adults and children, and is a major contributor to a number of diseases including type 2 diabetes, cardiovascular disease and some cancers. Current weight loss strategies using either lifestyle modification (diet and exercise) or drugs are relatively ineffective in the majority of obese individuals. This is partly due to the fact that we have an incomplete knowledge of the factors that regulate weight in humans. In laboratory studies we have shown th ....Obesity is becoming more common in Australian adults and children, and is a major contributor to a number of diseases including type 2 diabetes, cardiovascular disease and some cancers. Current weight loss strategies using either lifestyle modification (diet and exercise) or drugs are relatively ineffective in the majority of obese individuals. This is partly due to the fact that we have an incomplete knowledge of the factors that regulate weight in humans. In laboratory studies we have shown that human fat cell development can be dramatically accelerated by fibroblast growth factor-1 (FGF-1). This growth factor is produced by human endothelial cells, which are cells that line the blood vessels in fat tissue. When human fat cell precursors (preadipocytes) are cultured in the presence of FGF-1 the preadipocytes divide much more rapidly than normal and, additionally, then develop into mature fat cells much more rapidly than normal. These processes involved in development of new fat cells form the basis of fat tissue expansion in the body. The effect of FGF-1 on human fat cell development is far greater in magnitude than that of other known factors that promote fat cell growth. The aim of this project is to determine the actual biochemical pathways that mediate the effect of FGF-1 in promoting fat cell growth and development. Results obtained will provide insight into the cellular and molecular mechanisms regulating expansion of fat tissue mass in humans. Research aimed at identifying these underlying mechanisms, or at potentially contributing or exacerbating factors, is critically important in development of novel and more effective approaches to prevention and treatment of obesity.Read moreRead less
ATR-X Syndrome: Role Of ATRX In Testicular Growth And Spermatogenesis
Funder
National Health and Medical Research Council
Funding Amount
$650,881.00
Summary
Infertility is surprisingly common and affects 1 in 20 Australian men. Testosterone and its receptor, the androgen receptor, are well known to be essential for spermatogenesis and fertility. We have identified an important regulator protein (ATRX) of androgen receptor activity and show that loss of function of ATRX in testes of mice leads to spermatogenesis defects. Identifying the molecular action of ATRX will lead to a better understanding of the underlying causes of infertility in men.
Mechanisms Of The Insulin-sensitising Effects Of AMPK Activation In Liver And Muscle.
Funder
National Health and Medical Research Council
Funding Amount
$454,500.00
Summary
Type 2 diabetes represents an escalating global health problem. In Australia 7.5% of the population has diabetes and another 16% insulin resistance (impaired action of insulin). Insulin resistance is closely associated with obesity, dyslipidemia, hypertension and cardiovascular diseases (Syndrome X) as well as diabetes. A high caloric intake (particularly with a high fat content) and a sedentary lifestyle are extremely important environmental contributors to Syndrome X and diabetes. One of the m ....Type 2 diabetes represents an escalating global health problem. In Australia 7.5% of the population has diabetes and another 16% insulin resistance (impaired action of insulin). Insulin resistance is closely associated with obesity, dyslipidemia, hypertension and cardiovascular diseases (Syndrome X) as well as diabetes. A high caloric intake (particularly with a high fat content) and a sedentary lifestyle are extremely important environmental contributors to Syndrome X and diabetes. One of the most exciting developments in the past few years has been the discovery that an enzyme, AMP kinase (AMPK), normally activated by exercise, may be involved in its beneficial effects. We have contributed to this exciting field by showing in an animal model that one dose of AICAR, a chemical agent which can activate AMPK, ameliorates the effects of insulin resistance in muscle and liver. Further very recent work has linked AMPK with various drugs (particularly glitazones and metformin) and hormones which can enhance insulin sensitivity. The goal of the experiments in this project is to determine the overall mechanism by which AMPK has ameliorating effects on counteracting insulin resistance. We hypothesize that the mechanism for this involves an effect of AMPK to reduce fat molecules accumulating within muscle and liver cells, and our studies will examine this hypothesis. Our studies should lead to a better understanding of how exercise and pharmacological activators of AMPK help in management of diabetes and insulin resistant states. In addition because AMPK activation enhances glucose metabolism by a separate pathway to insulin, it offers promise of developing compounds able to bypass metabolic steps impaired by insulin resistance. Our studies should help in the design of new therapeutic agents which can counteract insulin resistance.Read moreRead less