19 December 2016

Are all obese individuals unhealthy?


Why are some overweight people affected by conditions such as diabetes and cardiovascular diseases whilst others who are overweight stay fit and healthy? New research from the University of Copenhagen may have found part of the explanation, which lies in three specific genes. In time, it may be possible to use the discovery for diagnosing and better treatment of metabolic diseases.

Being overweight can lead to serious metabolic conditions such as diabetes, inflammation of the liver and cardiovascular disease. But not all who are overweight fall ill. In fact, 10-15% of all those who are overweight are not ill. The reason may be down to three specific genes. This is revealed in new research from the Faculty of Health and Medical Sciences at the University of Copenhagen. The discovery could lead to better diagnosis and treatment of disease, reports Haja Kadarmideen, who is a Professor and Head of Quantitative Genetics and Systems Biology.

“We have investigated thousands of genes in the human genome and discovered that there are three genes which behave differently in healthy overweight individuals and those with metabolic disease. These three genes are strongly linked to many hundreds of other genes in gene networks and may be compared to “airport hubs”. If there are problems in a major airport hub, it affects all flights in the region. The same applies to ”hub” genes. In this instance, we have identified three genes whose behaviour is significant for the extent to which an overweight individual develops metabolic disease. This paves the way for being able to diagnose, develop drugs and target treatment at the specific genes," says Haja Kadarmideen.

One of the things that these genes may affect in healthy and ill groups of overweight individuals, is the expandability of adipose tissues which acts as fat stores in the body. The elasticity of these fat deposits appears to be affected by the genes that we have discovered. Imagine that you have a bag that you fill with water. If you keep on pouring in water, at some point it will overflow. The more elastic the bag, the more water you can pour in. Fat deposits function in the same way. In an obese individual with metabolic disease, the deposits are not so elastic and so the fat overflows faster and spreads into the blood steam and the rest of the body.

Found needle in the haystack
In order to identify the genes that were to blame for the differences in elasticity, the research team gathered fat and tissue samples from a seriously obese group (average BMI over 45) and split them into two groups: those who were healthy and those with metabolic disease. They then used Big (genomic) Data to compare complex datasets from the trial subjects to identify differences in the behaviour of the thousands of genes in the healthy and sick individuals. A process that Haja Kadarmideen describes as looking for a needle in a haystack. The process was only possible because of close collaboration between clinical professors and systems biologists who applied advanced sampling techniques and integrative systems biology methods, respectively. International collaboration between Denmark and the Netherlands played an important role, reports postdoc Lisette Kogelman.

”Many different kinds of tissues are involved in a condition such as obesity. It is difficult to take samples of the different types of tissue but in this instance, Maastricht University Medical Centre took tissue from patients that were undergoing obesity operations and we got permission to use them for further research. Collaborations like this are absolutely crucial for us to learn more,” she says.

Even though the researchers have made some important discoveries, this is only the first step on the way to a better understanding of the importance of these genes for metabolic diseases in severely obese individuals, emphasises Haja Kadarmideen. The next step is to get funding to undertake an even bigger research project in Denmark to validate the results.

This study was conducted as a part of the BioChild project, a large strategic research project on genetics and systems biology of obesity financed by the Danish Innovation Fund led by Haja Kadarmideen. The study is a result of collaboration between the University of Copenhagen, the University of Groningen, Maastricht University and the Atrium Medical Center Parkstad in the Netherlands. The article has been published in an internationally scientific journal, PLOS ONE. You can read it here.

Professor and Group Leader of Quantitative Genetics and Systems Biology Haja Kadarmideen
E-mail: hajak@sund.ku.dk 
Telephone: +45 35 33 35 77, Mobile: +45 23 83 98 90

Postdoc Lisette Kogelman
E-mail: Lisette.kogeman@regionh.dk
Telephone: +45 42 73 45 88