Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Please could you explain what oxidative stress is?
Even though oxygen is essential for us to live, it can react with other compounds in the body to produce molecules called free radicals, which are highly reactive and damaging.
Oxidative stress describes the situation in which too many free radicals are produced for the body to cope with. It is the reason that there are so many antioxidants available on the market – to try to counteract some of this oxidative stress.
Please could you explain how antioxidants counteract oxidative stress?
Antioxidants act in the cell to mop up free radicals before they can react with important cellular targets like DNA and protein. Our bodies already contain many antioxidants in the form of enzymes, and in a balanced diet we ingest many naturally-occurring antioxidants, such as vitamin C, vitamin E, flavonoids (in tea and wine) and carotenoids (in fruit and vegetables).
Please could you define obesity?
The classical definition of obesity is the accumulation of excess body fat, to the extent that health is compromised, and it is often measured by parameters like body mass index (BMI).
At the level of the fat-storing cells (adipocytes), obesity is defined as the simultaneous build-up of fat in these cells and an impaired ability to break down this fat for use as a fuel.
What is currently known about the relationship between oxidative stress and obesity?
Oxidative stress plays an important role in natural aging processes, but it is also involved in many diseases from cancer and heart disease to neurodegenerative diseases such as Alzheimer’s.
Recently, evidence has begun to emerge that oxidative stress may be linked to obesity. For example, one of the features of obesity is the increased production of fat cells (called adipocytes), and it has been shown that oxidative stress in the environment around the cell can increase this process. But what we don’t know is how oxidative stress can affect processes that are taking place inside the cells themselves.
How much is known about the mechanisms by which excessive oxidation can lead to obesity?
Currently, little is known about the cellular mechanisms by which oxidative stress causes obesity. There are many ideas floating around, but it is important to have experimental results that can give clear answers.
Please could you outline some of the theories that have been proposed?
The theories try to explain the cause and effects of increased oxidative stress in obesity. Regarding excess oxidation, it is currently believed that excess fat leads to increased oxidation, particularly in fat-storing cells, which are the cells we are studying.
This oxidative stress could then contribute to obesity in a number of different ways. For example, it might cause an increase in the number of adipocytes, by increasing their rate of production. On the other hand, oxidative stress might change the behaviour of adipocytes, by affecting their ability to break down fat for use as fuel.
What types of experiment need to be performed in order to test these theories?
An understanding of the links between obesity and oxidative stress requires two broad classes of experiments. Firstly, we need to study the effect of oxidative stress on different functions of adipocytes (such as the production of new adipocytes, and their ability to break down fat). Secondly, we need to monitor oxidative stress in adipocytes, to see how it changes as the cells mature and function, and particularly when they start to function like cells in obesity.
You have recently been awarded a Ramaciotti Establishment Grant to study "The role of oxidative stress in obesity". How are you planning to study the links between obesity and oxidative stress?
We are developing small chemical tools that can give us information about oxidative stress. These are fluorescent dyes, which emit light that can be measured by a microscope.
For our dyes, we aim for fluorescence properties that change under different levels of oxidation. So for example, the molecule might be very strongly fluorescent under conditions of high oxidative stress, but only weakly fluorescent under normal conditions. Or it might fluoresce a red colour when oxidised, but a yellow colour when reduced.
We then plan to treat adipocytes with these dyes, and we can measure the fluorescence under a microscope. In this way, we can observe the oxidative stress that is being experienced by healthy cells compared to cells that exhibit obesity-like behaviour. We can also test the effect of antioxidants on the oxidative stress of adipocytes.
How long is this research likely to take?
The grant is for two years, and in this time we can begin to develop preliminary sets of dyes and study their behaviour in cells. The research project will continue beyond that time, as we develop even better dyes, and are able to answer more and more complicated questions.
What impact do you hope your research will have?
Firstly, we will have developed tools that can be used by researchers interested in studying oxidative stress in many different diseases, far beyond the scope of obesity.
Secondly, we anticipate that the research will also uncover some of the cellular mechanisms that underpin obesity.
Finally, we hope that this greater understanding will lead to the development of new ways to treat obesity.
Do you think that one day there will be treatments for obesity?
As with so many other diseases, obesity results from a complicated interplay of many different genetic and environmental factors, so all cases cannot be treated in the same way.
But I think that, as we understand more and more about how obesity arises at the level of the cell, it will be possible to design treatments that address the condition more effectively.
Where can readers find more information?
The work of the group can be found here http://www.chem.usyd.edu.au/~enew/
For further information on the Ramaciotti Awards: http://www.perpetual.com.au/ramaciotti/
About Dr Elizabeth New
Elizabeth New obtained her BSc and MSc degrees from the University of Sydney, and then held a Commonwealth Scholarship at Durham University (UK) where she received her PhD in 2009. After that, she was a Royal Commission for the Exhibition of 1851 Postdoctoral Fellow at the University of California, Berkeley, and was awarded the RSC Dalton Young Researchers Award in 2011 for this work.
Elizabeth has recently begun her independent career at the University of Sydney with a Discovery Early Career Researcher Award from the Australian Research Council. Her group is working at the interface between chemistry and biology, developing chemical tools that can be used to understand aspects of biological systems such as oxidative stress and the role of metal ions.