Patrick Schrauwen Patrick Schrauwen

Muscle fat and diabetes

In Body
Written by  Femke Kools Monday, 03 January 2011 08:58

Vici laureate Patrick Schrauwen

These days, adult-onset diabetes is no longer just reserved for the elderly. People develop Type 2 diabetes mellitus at increasingly young ages; this is the diabetes that is not congenital, but is brought on by an unhealthy lifestyle. Obesity plays a role, but so too, according to some scientists, does inactivity. Several researchers at Maastricht University are convinced that accumulated fat in the muscles plays an important part in the onset of Type 2 diabetes – and that you can prevent the fat in these muscles from having harmful consequences through regular physical exercise.

Around one million people in the Netherlands currently suffer from Type 2 diabetes, and they are joined by 200 new cases every day. Together with colleague and friend Dr Matthijs Hesselink, Dr Patrick Schrauwen heads a research team which has tenaciously followed its own hypothesis for years. Recently, its research has brought in several grants, including the Vici grant of the Netherlands Organisation for Scientific Research (NWO) for Schrauwen.

“This means recognition for the research team and me personally”, he says. “It’s the most prestigious grant in the Netherlands, which is great to be awarded. It enables you to put your research on the map again within the university, faculty and department. We really add to this internationally competitive field, and we can be proud of that.”

‘This field’ is that of research into diabetes at an early stage, in particular with regard to metabolism. More specifically, Schrauwen examines the molecular aspects of the disease. Last year he proved that people with adult-onset diabetes have less active mitochondria (the ‘powerhouses’ of the cells) in their muscles than healthy people.

“There are indications that this is caused by fat accumulation in the muscle”, he says. “I want to use the Vici grant to prove this. The location within the body where the fat accumulates determines the health risks of obesity. I’m convinced that more physical exercise plays an important role in preventing harmful fat storage in the muscles and organs.

“In addition, mechanisms exist that protect the muscle from the detrimental effects of fat accumulation. I will examine whether these mechanisms are reduced in people with a predisposition to diabetes. I suspect that the UCP protein is involved in this mechanism.”

‘Lose weight’

Schrauwen strives to have more public attention paid to fat accumulation in the muscles, so it can be treated in a more focused manner than simply with the general doctor’s advice of ‘Lose weight’. Because it is still difficult for GPs to measure whether there is fat in the muscles, Schrauwen and his colleagues hope to discover a biomarker which makes it simpler to measure muscle fat in practice.

“The Netherlands has long been a small country with an active population, but we’re gradually moving more towards the United States’ situation”, he warns. “We should generate attention for that. This disease can largely be combated by a healthy lifestyle, so I’m not primarily searching for a new drug. If we ever demonstrate a relationship between the UCP protein and the protection mechanism, I think the pharmaceutical industry will be interested in producing a drug which activates that mechanism. But in my opinion, pharmaceutical interventions play supporting roles to lifestyle, not the other way around.”

Mice

Schrauwen and his team’s work comprises animal and human research. They use scanners to image fat accumulation and examine muscle tissue samples. “Laboratory animals are essential to this type of fundamental research. For example, in mice you can knock out the UCP protein for the purpose of research, which you can’t do in people. But ultimately you don’t want to cure mice. It’s important to me to maintain the broad perspective of my research. While the core of the issue lies at the molecular level, I don’t feel it is useful to study biological mechanisms without an applicable aim.”

Schrauwen and Hesselink have always persevered in striving to achieve that aim, though their hypothesis challenges the established scientific view. Schrauwen: “A few years back, Professor Shulman, a leading scientist in this field at Yale University, postulated that poorly functioning mitochondria were responsible for the accumulation of fat in the muscles. We think it’s the other way around. I recently heard Shulman say that our hypothesis may very well be true too – that’s a wonderful compliment for us.”

Coincidence

Besides tenacity, coincidence has also played a role in Schrauwen’s successful research career. “My doctoral research revolved around fat burning. In 1997 I submitted a scientific article, and one of the reviewers commented that I should elaborate on the possible role of the UCP protein. At the time I was more into physiology rather than fundamental molecular biology, so it didn’t mean much to me. Also, because I couldn’t measure it in my Maastricht research design, all I could do was add a line or two in the discussion section of that article.

“According to my supervisor at that time, though, the future of biomedical research was in molecular biology. For that reason I spent the last six months of my doctoral research in Phoenix, Arizona, and that’s where, when the opportunity presented itself, I suggested researching the relationship between the UCP protein and energy metabolism. This soon led to interesting results and publications. I’m still working on that protein, also together with the researchers in Phoenix.

“Those last six months in Phoenix formed the basis for my current research, for which I received an NWO fellowship [the current Veni grant – eds] that got me started after my return to the Netherlands. So in fact, I really owe that reviewer for putting me on the path towards my current research with that one comment. It’s amazing how these things turn out.”

Dr Patrick Schrauwen is a researcher at the Department of Human Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University. His research is also part of the Nutrim research school. Contact: This email address is being protected from spambots. You need JavaScript enabled to view it.

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