La Trobe University neuroscientist Richard Weisinger's decade-long research into nutrition and body weight found itself in the glare of world-wide media attention recently suggesting that popular blood pressure drugs may one day be re-badged to combat obesity.

And waiting in the wings of his first floor laboratory on the main Melbourne campus at Bundoora is a new project that takes a 'hair of the dog' approach to the same problem – probing by-products from sugar refining in the quest for a 'natural' anti-obesity drug.

The reports of a 'promising miracle weight-loss pill' based on blood pressure drugs followed publication of his research in the prestigious journal Proceedings of the National Academy of Sciences (PNAS) in the US. So far the drugs – called ACE (angiotensin converting enzyme) inhibitors – have been primarily tested on laboratory mice and rats for their weight loss effects.

Experiments by Dr Weisinger, an associate professor in psychology, and other scientists from La Trobe, Deakin University and the Howard Florey Institute found that mice lacking angiotensin II weighed twenty per cent less than their normal counterparts and had fifty to sixty percent less body fat, particularly in the abdomen. They also processed sugar more quickly, suggesting they were at lower risk of diabetes.

Dr Weisinger – who worked with La Trobe colleagues Dr Mark Jois from Agricultural Sciences and Denovan Begg from the School of Psychological Science – told leading science writer Leigh Dayton from The Australian that the link between weight loss and ACE came about purely by chance in earlier experiments.

'Our group was using an ACE inhibitor with animals to study the effects on blood pressure of a complex biochemical pathway called the "reninangiotensin system". Unexpectedly, the mice and rats got skinnier. When I saw the body weight was down I said that's phenomenal. We should get right into that. And that's what we did.' Angiotensin II is a very potent chemical that cause muscles around blood vessels to contract, thereby narrowing them which leads to high blood pressure.

Dr Weisinger explains that fat cells store excess energy for times when food is scarce, which is rarely an issue in modern western society. They also contain the renin-angiotensin system that helps regulate formation of fat cells and the ability of fat cells to store fat, in addition to their well-known influence on blood pressure and blood volume. Drugs that block a key step in this system can cause weight loss, but how they do this is unclear.

Various experiments by Dr Weisinger and colleagues over many years have explored this question in laboratory mice engineered to lack the gene that encodes the key angiotensin converting enzyme.

The results, published in PNAS, confirm the critical role of this system on the growth of fat tissue and suggest a mechanism by which drugs that interfere with the system might spark weight loss.

Given widespread concerns in much of the developed world about body weight and health, Dr Weisinger expects that human trials based on these results may well start within a year. But he is quick to caution that pressing this existing class of blood pressure drugs into service against obesity is unlikely to be a panacea, or lead to a 'miracle' pill.

'I don't think we'll see it added to the water supply any time soon. There are issues of not inconsiderable possible side effects that doctors have to weigh up today when they prescribe these drugs for high blood pressure.'

Second 'ace'

But Dr Weisinger reveals he may well have a second 'ace' up his sleeve. He has applied for a research grant to probe byproducts from sugar refining – polyphenols found in molasses – and, perhaps, use these to develop a 'natural' drug.

He says molasses are a significant waste stream of the sugarcane industry and very rich source polyphenols, different from those found in tea, cocoa or red wine which are often touted for their ant-oxidant qualities in keeping our blood vessels healthy. Several different extracts have been produced from molasses, each containing their own unique combination of polyphenols.

'We are hoping to show that these polyphenols in waste products from sugar refining can be used to improve body weight and insulin sensitivity.

'Our aim is to determine the influence of each of these extracts on body composition and insulin sensitivity and their mechanisms of action and to gather basic scientific information that may make the sugar industry more health-oriented and productive.'

This, he says, ultimately would have enormous implications for human health and disease. It would also be of great national benefit for a billion-dollar industry whose main product, refined sugar, is calorie rich but nutrition poor – and a major contributor to the ever increasing problem of obesity and metabolic syndrome which has huge costs for the Australian health system.

Fatty acids in diet

Dr Weisinger came to La Trobe's School of Psychological Sciences in 2005 from the Howard Florey Institute, where he maintains an honorary appointment. He also continues research ties with the Southwest Foundation for Biomedical Research, San Antonio, Texas. His studies examine links between the progression of disease and early diet, particularly the 'Western Diet' and the benefits of Omega-3 fatty acids, as well as the neural pathways that mediate disease and how they are altered by diet. He and members of his laboratory are also probing how biological systems influence eating patterns, cardiovascular and neural function. They are interested in the neural pathways that control a person's 'body weight set point' and factors that influence it.

For the last three years Dr Weisinger has also led an international team in a $277,000 National Health and Medical Research Council study that has helped establish the benefits from consuming Omega-3 fatty acids. These are found in fish such as mackerel, herring, sardines, certain types of tuna and salmon and in the oils of soybeans, canola, walnut and flaxseed.

For example, Dr Weisinger's work with laboratory rats has helped establish that Omega-3 fatty acids are important to pregnant and nursing mothers. He has shown that putting a pregnant healthy female rat on a low Omega-3 fatty acid diet resulted in poorer milk and less healthy offspring who develop high blood pressure as adults.

'Humans evolved as hunter-gatherers with a fatty acid diet in which Omega-3 and Omega-6 fatty acids (found in animal fats and oils, most vegetable fats and oils and dairy fats) existed in roughly equivalent amounts,' says Dr Weisinger.

'But in modern Western society we now consume between ten and twenty-five times more Omega-6 than Omega-3 fatty acid. This becomes a major problem because both Omega-6 and Omega-3 fatty acids compete for the same metabolic enzymes.'

The Omega-3 and body weight studies also involve collaborations with scientists from Deakin University, the University of Melbourne, the Hungarian Academy of Sciences and the University of Peradeniya, Sri Lanka.