Sixty percent of adults and thirty percent of children in Australia are overweight or obese. Many of these individuals have obesity-related health issues including diabetes and heart disease.
Current Laboratory Members
Professor John Prins: Dr Ingrid Hickman, Dr Tony Russell, Associate Professor Graeme Macdonald, Dr Louise Hutley, Dr Tony Bachmann, Associate Professor David McIntyre, Dr Clair Sullivan, Dr Jennifer Martin, Dr Trisha O'Moore Sullivan, Dr Stephanie Ipavec Levasseur, Ms Janelle Nisbet, Mr Thien Nguyen, Ms Cynthia Ong, Ms Liza Phillips, Ms Ilaria Croci and Ms Sohinee Sarkar.
Dr Michelle Hill: Ms Dorothy Loo and Mr Robert Luetterforst.
The Metabolism and Clinical Metabolic Groups undertake basic and clinical research into factors underpinning the relationship between obesity and metabolic disease. Studies range from analyses of factors regulating growth and metabolism of human adipose tissue in vitro through to examining the impact of lifestyle modification on cardiovascular function and glucose metabolism.
Current Research Projects
Obesity and FGF-1
We have identified FGF-1 as a potent stimulating growth factor for the growth of human fat cells. Our current work explores the therapeutic possibility of strategies to impair FGF-1 action to promote weight loss. Results to date indicate that pharmacological and gene knockdown approaches can reduce fat cell growth in vitro; and reduce adiposity in animal models of obesity.
Glucocorticoids and insulin resistance
Glucocorticoid hormones, which are increased in obesity; and glucocorticoid drugs, which are widely used in asthma and arthritis, cause impaired glucose tolerance and, in some individuals, diabetes. We are using human adipose cells to investigate the mechanisms behind this phenomenon. Information gained may allow us to develop ways to prevent the damaging side-effects of corticosteroids.
11betaHSD-1 and its relationship to metabolic dysfunction 
11betaHSD-1 is an enzyme in adipose tissue that produces glucocorticoid hormones. We have demonstrated that the expression and activity of 11betaHSD-1 is increased in adipose tissue of obese individuals, suggesting that increased glucocorticoid may contribute to the metabolic dysfunction seen in obesity. We are currently investigating the efficacy of drugs that specifically block 11betaHSD-1 activity, as potential anti-diabetes strategies.
Food and inflammation
Food is known to induce inflammation which, in turn, may induce hypertension and abnormal glucose tolerance, leading to diabetes. We are investigating the inflammatory, pro-oxidant, blood pressure and hormonal response to a standardised breakfast in lean, obese and diabetic patients. If the responses vary in the subject groups, insight may be gained into diet-related factors that may lead to metabolic diseases such as diabetes, heart disease and hypertension.
Lifestyle intervention in obese subjects
This study is investigating the effect of metformin (a drug to improve insulin action) and lifestyle intervention in subjects with obesity. The aim of the study is to determine if an effective program of weight loss achieved with calorie restriction and physical activity will improve metabolic and cardiac function. This study is performed as part of our NHMRC Centre for Clinical Excellence in Cardiovascular and Metabolic Disease grant and NHMRC Partnership Grant in Type 2 Diabetes. 
Intramyocellular and intrahepatic lipid studies
In subjects with obesity and/or diabetes, “ectopic” fat is stored in many tissues, notably muscle and liver. In these sites, the fat interferes with normal function of the tissues. Paradoxically, endurance athletes (who are neither obese nor diabetic) also store fat in muscle, but for the purpose of energy storage for muscle contraction. We used magnetic resonance spectroscopy to study the effect of acute exercise on liver and muscle fat storage in obese men before and after a weight loss program (leading to a 10kg weight loss). Preliminary results show that liver fat is reduced by over 40%, but muscle fat content is unchanged.
Professor Prins is currently offering postgraduate projects in his laboratory. Click here for more information.
Dr Michelle Hill's Research
Obesity, Barrett’s oesophagus and oesophageal adenocarcinoma
Oesophageal adenocarcinoma has a very poor prognosis, with less than 20% patients surviving 3 years after diagnosis. The incidence of oesophageal adenocarcinoma and its pre-cancer condition called Barrett’s oesophagus, rapidly increased over the past 20 years. This parallels the obesity epidemic, and indeed obesity increases the risk of Barrett’s oesophagus and oesophageal adenocarcinoma, in addition to other risk factors including smoking, gastro-oesophageal reflux disease, male gender and being greater than 50 years of age. We are using proteomics and cell biology techniques to determine the molecular link between obesity, male gender with risk of Barrett’s oesophagus and adenocarcinoma.
Caveolin and statins in prostate cancer metastasis
Prostate cancer is the most common cancer in men in Australia, and is the second most common cause of cancer deaths in men. Localized prostate cancer is curable if detected early. Prognosis is much worse when the cancer has metastasized (spread) to other organs, most commonly lymph nodes, bone or brain. Recent meta-analysis reported that statin therapy reduces the risk of aggressive prostate cancer. Statins, drugs commonly used to treat high blood cholesterol, acts by inhibiting an enzyme in cholesterol synthesis pathway. We have recently shown that modulating the subcellular structure of caveolins, a protein on the cell surface that binds cholesterol, can reduce the aggressiveness of a prostate cancer metastasis-derived cell line. Using proteomics techniques on the prostate cancer cell model, we will perform a systems analysis to determine which cellular pathways are modulated by statin therapy and/or changes in caveolin organization. This project will identify candidate therapeutic targets for treatment of aggressive prostate cancer.
Lectin array for identifying biomarkers for cancer and diabetic neuropathy
Sensitive diagnostic tests, such as the PSA blood test for prostate cancer, greatly improve patient diagnosis and disease survival. We are developing a novel semi-automated high throughput proteomics method for identifying and validating new markers for diagnosis and classification of diseases. We will apply the technique to discover tear biomarkers for diabetic neuropathy (in collaboration with Dr Anthony Russell and the Anterior Eye lab at QUT), and blood biomakers for Barrett’s oesophagus and oesopohageal adenocarcinoma (in collaboration with the Study of Digestive Health, lead by Dr David Whiteman, QIMR), breast cancer (in collaboration with Prof Sunil Lakhani and Dr Peter Simpson, CCR UQ) and prostate cancer (in collaboration with Australian Prostate Cancer Bio-Resource).
Post-graduate projects are available, please contact Dr Hill for details.