2005 Successful NHMRC Project Grants

This project is about the study of central regulation of energy balance contributing to protection or development of chronic high-energy diet-induced obesity. Obesity is a major predisposing factor for a variety of life threatening diseases such as type II diabetes, hypertension, and coronary heart disease with their enormous costs both socially and financially.

Development of human obesity and its related metabolic disorders is a long term process generally develops over a long period and eventually becomes a chronic condition. Generally, chronic consumption of high-energy food in excess of expenditure leads to excessive fat accumulation and promotes the development of obesity. However, studies on both humans and experimental animals have revealed that not all individuals become obese on a high-energy diet; thus, individual susceptibility is an important phenomenon allowing us to search for the genes contributing to the individuals' susceptibility or resistance to diet-induced obesity and to identify for effective targets for both prevention and treatment of obesity. Using the animal models developed in our laboratory, the proposed research aims to demonstrate the differences in the central regulation between the mice resistant or susceptible to the development of chronic high-energy diet-induced obesity.

Outcomes of this project will provide us with: 1) better targets for the prevention of diet-induced obesity; (2) more effective treatments for the late stage of obesity and its related metabolic disorders; and (3) a better understanding of the individual susceptibility to diet-induced obesity.

Children who are obese have a higher risk of numerous health problems, including high blood pressure, high cholesterol and joint problems. They also experience reduced self-esteem and discrimination as well as an increased risk of premature death or poor health due to heart disease and Type 2 diabetes in adulthood. Approximately 25% of Australian children are overweight or obese. This prevalence has doubled since the 1980's and is still increasing. Child obesity is a major public health problem and innovative approaches to solving this problem are urgently needed.

A range of factors has been postulated as contributing to the global childhood obesity epidemic, including environmental, psychosocial, physical, nutrition, metabolic and lifestyle factors. However, the major determinants involve a shift away from energy balance through reduced energy expenditure or physical activity and increased energy intake.

Conventional weight-management strategies have incorporated restricting energy intake or diet, increasing energy expenditure or physical activity, decreasing sedentary activities, parental involvement, and behaviour modification. However, these strategies have only shown moderate success among children in the medium to long term and very few can be translated into community settings.

The purpose of this study, and its original contribution to research, is to determine the impact of a physical activity skill development and parent-centred family weight management program on the weight, cardiovascular health, physical activity, dietary intake, and sedentary behaviours of overweight and obese children.

Prostate cancer is one of the most commonly diagnosed cancers in men over 55 years of age. Approximately 30% of all diagnosed cancers in this age group are prostate carcinomas. Low and high dose rate brachytherapy are newly established treatment options for early-stage, low-risk, prostate cancer and are an alternative to curative prostatectomy in most patients.

Local control and cure of prostate cancer is greatly influenced by the dose distribution generated by both the treatment techniques. Treatment plans must be able to deliver a prescribed dose in the tumour, with adequate margins, while minimising the dose delivered to the surrounding normal tissue and critical organs. It is well recognised that, however skilful the radiation oncologist, an ideal dose distribution according to a treatment plan does not guarantee a well delivered dose. Complications such as impotence, severe radiation urethritis and severe rectal bleeding will arise if overdosing of the neuro-vascular bundle, urethra and rectum occurs respectively.

This project is based on newly developed instrumentation that will allow continuous, realtime, in vivo, monitoring of the radiation dose levels in the urethra and rectum during brachytherapy treatment of prostate cancer. Such monitoring of the treatment procedure, has been identified as a high priority by the American Brachytherapy Society. The technique will allow extensive in vivo and post treatment studies to be performed by clinicians so as to measure the dose levels currently received and identify the optimum acceptable dose levels for future procedures.

The outcomes of this project may well be able to be utilised in other forms of brachytherapy treatment (e.g. breast, cervical cancer) and other radiation treatment modailities (e.g. conventional radiotherapy and intensity modulated radiotherapy) to also reduce complications associated with these treatment modalities.

This study adds significantly to our knowledge of the effect of diet composition on weight management. It builds on animal model studies demonstrating the effects of different types of fat on obesity development, and on our research in people with diabetes, where we found a higher proportion of polyunsaturated fats in a low fat diet resulted in greater body fat loss. Our proposed research will demonstrate whether this same dietary profile can reduce visceral fat in people who are overweight but not diabetic, and whether we need to reduce calories or not to achieve this end. It may be that the effect is due to a higher level of fat used as fuel, a higher metabolic rate, or a reduction in appetite. We will be able to determine these effects, and add to the scientific knowledge base of dietary components and energy balance.

Having this knowledge is important if we are to develop dietary advice for weight management that is more specific and effective than general statements on eating well. One of the great strengths of this study is that the food guidance system is fully developed. Not only will we will prove the targeted nutrient composition of the diet is achieved, the food guidance system provides for people to chose foods under free living conditions. Thus the link to this research and clinical practice models will be assured. The impact of this research may then be assessed in terms of more effective clinical strategies for the management of obesity, a major public health concern.