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Studying the role of inflammation in obesity

15 February, 2017

YOUNG RESEARCHERS. Researcher Emma Börgeson is working on a hypothesis that might mean more people with obesity-related diseases can stay healthy. Soon, she will develop her line of research, as one of the young researchers recruited to the Wallenberg Centre for Molecular and Translational Medicine in Gothenburg.

When Emma Börgeson tells us which researchers she is collaborating with in Gothenburg, the list becomes long even though she has been a visiting research fellow at the University of Gothenburg for a short time. She is a visiting research fellow at the Wallenberg Laboratory at the Institute of Medicine, conducting a study of human tissue samples with Gastlab, which belongs to the Institute of Clinical Sciences. She has also established cooperation with Marianne Quiding-Järbrink at the Institute of Biomedicine. She has found ideal conditions in Gothenburg to go further with the line of research she established as a post-doc in San Diego.

“I find all prerequisites can be found here to promote a successful research program and I feel really welcome. I have received help and support from my new colleagues and I am impressed at how well the translational collaborations between the University of Gothenburg and Sahlgrenska University Hospital work,” says Emma Börgeson.

She previously received an establishment grant from both the Swedish Research Council and the Swedish Society for Medical Research (SSMF), which are funding her research. Soon, she will begin her research position at the Wallenberg Centre for Molecular and Translational Medicine. It is a four-year assistant professor position with associated research funding to establish her own research team. The position is being appointed with a so-called tenure track, which means it probably will later be converted into a permanent position. Another two young researchers have been recruited in the effort and more requests for proposals are underway. Ten researchers will be employed in the Wallenberg Centre for Molecular and Translational Medicine in Gothenburg.

The surgeon Ville Walenius, Assistant Professor in the Institute of Clinical Sciences, collaborates with Emma Börgeson in a study of tissue samples from humans. In connection with the gastric bypass surgery at Östra Hospital, samples of human tissue are collected to be used in research.

A new strategy for obesity

Emma Börgeson is conducting research on obesity and related complications. In Sweden, a growing number of people are suffering from obesity-related complications, causing an extensive burden on healthcare services and society.

“Not all overweight people develop disease, which is something that’s often forgotten in the debate. These “metabolically healthy” individuals seem to live for decades without elevated lipids, diabetes, or other diseases,” says Emma Börgeson, whose research objective is to understand why some people remain metabolically healthy, and try to promote metabolic health with the anti-inflammatory substance lipoxin.

Obesity in itself does not appear to be the primary cause of the obesity-related complications. Rather, we speculate that obesity-related inflammation may be the initiator that drives disease.

“I have been fascinated by how the body regulates inflammation. Inflammation is regulated by signals that first ‘turn on’ and then ‘turn off’ inflammatory processes, to ensure an adequate defense. If this balance is disturbed, a person may develop chronic inflammation, which we believe can cause, for example, obesity-related complications.”

Her hypothesis is that metabolically healthy individuals may have a better ability to “turn off” inflammation, through the formation of anti-inflammatory substances called lipoxins. Lipoxins are a group of lipids that “turn off” inflammatory processes. In a noted study published in the journal Cell Metabolism, she showed that lipoxin treatment attenuates obesity-induced inflammation and organ disease in mice. Importantly, the protection is independent to weight loss.

Emma is now treating human tissue with lipoxin ex vivo, to study if the same principle applies to humans and if it is worth continuing along the long path that remains before the idea can lead to a new medication.

Complementing lines of research

In the third and final year of her Marie Curie sponsored post-doc, Emma Börgeson was to return from UC San Diego to her home university, University College Dublin. But when the intended clinic where she was to get patient biopsies in Ireland suddenly closed, she had problems conducting her intended study. Her colleague, Carel le Roux, then suggested she contact the clinic-near research group Gastlab at the Department of Gastrosurgical Research and Education, where Carel is also a visiting professor. At Gastlab, Emma Börgeson received a warm welcome by Department Head Lars Fändriks and Docent Ville Wallenius.

Ville Wallenius, researcher at Gastlab and experienced obesity surgeon at Sahlgrenska University Hospital, and Emma Börgeson conduct the EPN-approved study Adipos2 together. Patients who choose to participate in the study donate fat biopsies that Emma uses in her experiments. This is done in connection with the patients’ planned gastric bypass operations at Östra Hospital.

“Our projects fit together like a hand in a glove. We are both interested in the same pool of patients and studying obesity and its complications with slightly different perspectives,” says Ville, who is a Docent in Applied Physiology and Pathophysiology:
“I study if obesity-related inflammation begins in the small intestine and Emma studies if lipoxin can function as an anti-inflammatory treatment in fat, the liver and the intestines. It’s an ideal opportunity to collaborate where we build on each other’s competencies.”

“It is stimulating to work with Ville and the clinic-near research environment has led me to want to develop this work at the University of Gothenburg. I think there are unique conditions here to conduct the translational research I am interested in,” says Emma.

Incubator on site at Östra Hospital

It is complicated to take patient samples from Östra Hospital and then analyze them at Sahlgrenska Hospital. Handling the tissue takes nearly two days. The research nurses at Gastlab have coordinated patient preparations with surgical times, to ensure that the tissue samples can be immediately analyzed. Until now, Emma has had to drive post haste to Sahlgrenska University Hospital with tissue samples to get them into an incubator quickly, but now the cell cultivation possibilities are also available at Östra Hospital. Through collaboration with Elinor Bexe Lindskog and Yvonne Wettergren at the Surgical Oncology Laboratory (SOL), Emma gains access to this infrastructure.

“The collaboration with the Östra surgical team and SOL is crucial for these experiments, and we are very grateful it works so smoothly. The faster the tissue gets into the incubator, the better. As we begin to extend the intubation time, it is critical that we have immediate access to tissue culture facilities,” says Emma.

Emma Börgeson holding a sample of human tissue taken in connection with a gastric bypass operation that has just been completed.

With the help of Gastlab, Emma has treated samples from 15 patients to-date, and the preliminary results are promising:
“The human tissue seems to be less inflamed when lipoxin is added. If the final results look as good, we can go on to investigate the principle in other animal models and eventually perhaps also move on to clinical studies, but of course that’s a long-term objective,” says Emma. The study will be underway for another four years and according to the plan, it will then comprise 80 patients.

Emma is now developing her research team through the Wallenberg Centre for Molecular and Translational Medicine. She will continue her close cooperation with Gastlab and establish herself at the Institute for Medicine and the Wallenberg Laboratory, a translational research platform on the hospital campus, comprising around 15 research teams. It has the specialized laboratory environment she needs.

“I have had a very warm welcome from Hans Carlsten and the institute of medicine, as well as Jan Borén and Fredrik Bäckhed who lead Wallenberg Laboratory. It’s a stimulating and well-functioning research environment and I’m looking forward to continuing to develop the collaboration with the groups that are active there. The Institute of Medicine feels like a promising platform for establishing my research team,” Emma confirms.

Via Dublin and San Diego

Emma Börgeson. Foto: Privat.

Emma Börgeson is originally from Borås and studied medical biology in Linköping. She then earned her doctorate at the Irish University College Dublin, sponsored by a grant from the Irish Research Council for Science, Engineering, and Technology (IRCSET). Her supervisor, Professor Catherine Godson, conducts research on how kidneys are affected in diabetes and was one of the first to work with lipoxins in this field of research. In her doctoral thesis, Emma evaluated chemically modified lipoxin molecules and how they affected kidney disease and diabetes.

A Marie Curie scholarship then gave Emma the chance to do her post-doc in the U.S., with Professor Kumar Sharma, who leads a translational research center on kidney diseases at the University of California, San Diego (UCSD). She met him at a scientific conference where she saw him present a new animal model. Emma realised the animal model entailed new possibilities to take the next step in her own research on lipoxins.
“I caught Dr. Sharma after the presentation and showed him a quick sketch on a piece of paper to illustrate what I would like to do with his mouse model. My drawing wasn’t very good, but he thought it seemed exciting and invited me to work with him,” Emma remembers.

Some ten researchers will be hired

The Wallenberg Centre for Molecular and Translational Medicine has been formed with support from the Knut and Alice Wallenberg Foundation and is a joint effort for the University of Gothenburg, the Västra Götaland Region and AstraZeneca. Emma Börgeson is one of the ten or so researchers who will be employed at the university through the effort. Another two researchers have been recruited and more requests for proposals are expected soon. With the teams formed around the recruited researchers, the effort means that some hundred new researchers with a translational approach will strengthen the already successful biomedical research conducted in Gothenburg.

Read more about the Wallenberg Centre for Molecular and Translational Medicine here: http://wcmtm.gu.se/

Here, you can read the article Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease. in Cell Metabolism: http://www.sciencedirect.com/science/article/pii/S1550413115002156

TEXT: ELIN LINDSTRÖM CLAESSEN
PHOTO: JOHAN WINGBORG

By: Elin Lindström
Tagged With: Samverkan, Samverkan

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