Targeting Inflammation to Fight Obesity-related Diseases

Obesity is considered a risk factor for diseases including diabetes, liver cirrhosis and chronic kidney disease. Adipose (fat tissue) inflammation seems to be a common denominator among these obesity-related diseases. Inflammation is part of the body’s natural response to injury. Lipoxins are molecules that help to clear or resolve inflammation. This research study set out to investigate the impact of a lipoxin, and a synthetic version of the molecule, in a laboratory model of obesity.

The findings, published online today (June 5th 2015) in the scientific journal Cell Metabolism, could support a new therapeutic approach to treating obesity and its associated conditions. Dr Emma Börgeson, first author and postdoctoral researcher with the Godson group who is currently working in the University of California San Diego said

This work aimed to mimic what occurs in the health but becomes subverted in disease. Our findings show that lipoxins reduced the extent of liver and kidney disease caused by a high-fat diet. We found that a particular lipoxin molecule (LipoxinA4) controls various cells of the immune system with the overall impact of reducing inflammation in adipose tissue and, as a result, protecting the body from the damaging effects of systemic diseases that occur as a consequence of obesity.

While the findings support the therapeutic potential of lipoxins, the team want to find a viable synthetic alternative that could be developed as a drug given that the molecule in its natural state is unstable and expensive to make. The research team included synthetic chemists led by Professor Patrick Guiry from UCD School of Chemistry & Chemical Biology ,Centre for Synthesis & Chemical Biology & UCD Conway Institute.

The research has shown that the synthetic analogue of lipoxin [15(R)-Benzo-LXA4], is also active, easier to produce and consequently more cost effective. This opens possibilities to explore the use of similar molecules with the potential for greater efficiencies and effectiveness while still being easy to produce and economic.

Professor Catherine Godson, Director of the UCD Diabetes Complications Research Centre in UCD School of Medicine and UCD Conway Institute said

The findings of this research study demonstrate the value and potential impact of fundamental research. Drawing on collaborative expertise in synthetic chemistry, molecular biology and translational medicine, the team have produced findings with significant potential to reduce inflammation, a critical driver of the devastating consequences of obesity-related diseases.

While this research study examined the action of lipoxin in a model of obesity, we will now focus on its action in models of chronic kidney disease induced by obesity and diabetes.

The research has been funded through a Marie Curie fellowship to Dr Börgeson and builds on previous research funded through Science Foundation Ireland and the Health Research Board.

Journal reference
Börgeson et al. Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease. Publi

UCD – Growing Research Programmes with Movember

In UCD Conway Institute, the Pennington and Watson groups have whole-heartedly embraced the challenge of growing and customising their facial hair for this great cause. The day job for each of the team members involves investigating the intricate workings of the disease and finding better tools for clinicians to diagnose prostate cancer earlier and improve the prognosis for patients.

Assessing your risk of getting prostate cancer is an important screening tool. Currently, a prostate biopsy is the standard method that clinicians use to diagnose prostate disease. The procedure itself carries a risk to patients of getting a blood stream infection and places significant costs and burdens on the healthcare system.

There is an unmet clinical need for a better method of assessing a person’s risk of having prostatic disease before moving on to such an invasive procedure as a biopsy. Using a blood test to measure levels of prostate specific antigen (PSA) as a screening tool on its own is not particularly satisfactory.

The Watson group have been working with colleagues in New York University and Galway University Hospitals to assess how two particular prostate cancer risk assessment calculators perform when used on a group of men from the West of Ireland. This unique group of 556 men had never been screened for prostate cancer, never had a prostatic biopsy before the study and only 2% had a family history of the disease.

One of the risk calculators developed in North America (prostate cancer prevention trial risk calculator or PCPT-RC) uses a particular set of criteria while the second was developed in Europe using a different set of criteria (European randomised study for prevention of prostate cancer risk or ERSPC-RC).

Professor Bill WatsonUCD School of Medicine & Medical Science and UCD Conway Institute, said

This is the first time that these two risk calculators have been validated in a contemporary Irish population. We found the PCPT-RC calculator performed better with this particular group, half of whom were found to have prostate cancer on biopsy. It was also the better tool to predict high grade disease. However, both calculators over-predicted the risk of cancer detection so there is more work to be done. We are now expanding this study to all patients that present to the rapid access clinics across Ireland with a view to building an Irish risk calculator.

Treating localised prostate cancer usually involves a combination of hormone and radiation treatment. For some patients, the disease reoccurs and there are no diagnostic tests that can predict this happening.

Among several prostate cancer projects including studies being undertaken in collaboration with the Dana Farber Cancer Institute at Harvard University, the Pennington group are trying to discover protein signatures in the blood that flag the risk of prostate cancer recurrence. Biomarkers able to address this issue would be of significant advantage to clinicians.

The team published findings of initial work that compared the protein signatures of a patient who experienced disease recurrence after hormone and radiation treatment with that of a patient who remained disease-free after treatment. The work is being undertaken as part of an ICORG clinical trial in association with radiation oncologist, Professor John Armstrong at St Luke’s Hospital.

Of the 287 proteins identified by the team, they saw changes in 95 proteins, selected 16 of these for further analysis and found them to be significantly associated with disease recurrence.

Professor Stephen Pennington, UCD School of Medicine & Medical Science and UCD Conway Institute said

While these results are promising, we need to conduct further research on greater numbers of patient samples to incorporate into our pipeline for biomarker discovery and evaluation and so identify a serum protein signature that can predict or monitor the outcome of treatment of patients with prostate cancer.

 

UCD Academic Centre for Paediatric Research Launched

Child health research is widely acknowledged as being underdeveloped in Ireland compared with that conducted in other areas. There have been concerns about undertaking research on children because of their vulnerability and the investigation of diseases in childhood has suffered, in part, because of this. However, it is now recognised that children are not simply small adults and it is not sufficient to rely on data from adult studies to inform decisions on how to investigate and manage diseases of childhood.

In a positive move towards addressing this imbalance, today saw the launch of the UCD Academic Centre for Paediatric Research which aims to unite academic and clinical research across UCD to inform decisions on how diseases of childhood are investigated and managed.  The Centre launch was marked by a symposium attended by the leading UCD affiliated researchers working at UCD Belfield and across affiliated children’s hospitals.

Speaking at the symposium, Professor Billy Bourke, Associate Professor and Consultant in Paediatric Gastroenterology at Our Lady’s Children’s Hospital, Crumlin and Director of UCD Academic Centre for Paediatric Research Director said

Research provides a basis for the development of excellence in clinical practice across the board by inculcating in health care workers and institutions a spirit of critical enquiry. The UCD Academic Centre for Paediatric Research will further facilitate the sharing of knowledge and expertise as we continue to strive towards making state of the art treatment and care available to our young patients.

The proposed National Paediatric Hospital will offer huge potential in the area of collaborative research for children in Ireland by centralising care for many conditions on one site. Professor Bourke commented

This type of centralisation – where children from all over the country can be involved in a study – allows us to make more accurate estimates of the occurrence of diseases, their impact on children, and their overall severity and outcomes. It will provide our children with the best possible care through a critical mass of healthcare professionals whose actions are evidence-based and informed by the latest medical knowledge. It will allow all Irish children who attend the hospital to participate in clinical research and provide access to blood samples and tissues from a wide spectrum of patients for research into the effects of novel treatments, the usefulness of various investigations and the importance of proposed underlying biological mechanisms.

Paediatric research programmes continue to rely heavily on the tremendous support received through philanthropic organisations such as the National Children’s Research Center, Our Ladys Childrens Hospital Crumlin and Temple Street Children’s University Hospital Research Group. Both hospitals were very well represented in relation to speakers at the symposium with presentations delivered on a diverse mix of topics relating to child health and paediatric research such as Paediatric Genetic Diseases, Childhood Obesity, Diarrhoeal Diseases of Childhood, Early Onset Epilepsy and Cystic Fibrosis. Full list of speakers available here.

UCD – First Point of Care Blood Test for Heart Disease in Malawi

A team of researchers from University College Dublin and Imperial College London have carried out a blood test for detecting early signs of heart disease for the first time in Malawi, Africa as part of a new research project for the management of type 2 diabetes.

When under stress, the heart releases a protein called a natriuretic peptide (NTproBNP), which can be used as a marker of cardiovascular disease in diabetes and other cardiometabolic conditions. The use of natriuretic peptides has been shown to be an effective method of targeting care and improving outcomes in people with risk factors for cardiovascular disease and heart failure1.

In collaboration with the Faculty of Health Sciences in Mzuzu University, further research will be carried out to use this test to identify early cardiovascular disease in diabetes in Africa. The Irish researchers donated a point-of-care machine and testing strips to the university to augment training for local medical scientists and enable this initiative.

The Managing Type 2 Diabetes in Malawi, Africa (MTIMA) project is a collaborative effort between University College Dublin, Imperial College London, Mzuzu University, Ungweru (Malawi based community outreach NGO), Luke International Norway (Malawi based ICT NGO), and the Ministry of Health, Malawi.

 

Training workshop for NTproBNP (Roche Diagnostics) point of care device in Mzuzu University. Pictured (l-r): Dr. Joe Gallagher (UCD), Dr. Mike Zulu (Dean and Head of Health Science, Mzuzu University Malawi), Dr. Chris Watson (UCD)
Training workshop for NTproBNP (Roche Diagnostics) point of care device in Mzuzu University. Pictured (l-r): Dr. Joe Gallagher (UCD), Dr. Mike Zulu (Dean and Head of Health Science, Mzuzu University Malawi), Dr. Chris Watson (UCD)

 

Training workshop for NTproBNP (Roche Diagnostics) point of care device in Mzuzu University. Pictured (l-r): Dr. Joe Gallagher (UCD), Dr. Mike Zulu (Dean and Head of Health Science, Mzuzu University Malawi), Dr. Chris Watson (UCD)

During this project, Dr Chris Watson (UCD Conway Institute & School of Medicine & Medical Science) and Dr Joe Gallagher (UCD School of Medicine & Medical Science), together with Dr John O’Donoghue, Imperial College London, will establish electronic decision support systems in the community and point-of-care blood testing to enable treatment of diabetes in the primary care setting.

Educating communities, patients and healthcare workers on the prevention and treatment of type 2 diabetes will be an important goal. The project will also develop standardised medication packs to simplify the delivery of diabetes therapies in the community and widen access to effective care.

Currently, it is estimated that 347 million people worldwide suffer from diabetes with more than 80% living in low and middle-income countries. Sub-Saharan Africa will see a rise in incidence of diabetes from 12.1 million in 2010 to 23.9 million in 2030. Just like the developed world, 90% of diabetes patients in Sub-Saharan Africa have type 2 diabetes. The current prevalence of diabetes in Malawi is 5.6%.

According to Dr Chris Watson, the scale of the problem is apparent and the issue of accessing care locally leads to patients presenting late with complications and difficulties with accessing medications occur on a regular basis.

“A survey that we carried out in collaboration with the local community group, Ungweru in Mzuzu showed that although 96% of local healthcare workers had heard of diabetes and 83% knew someone with diabetes, no healthcare worker was aware of guidelines for the management of the disease.

65% of these healthcare workers had no access to a method to measure blood pressure and 26% felt that they would do nothing if they thought someone had diabetes as there were no facilities available to manage the disease. In this country of almost 16 million people, there is only one hospital that can test HbA1c, a vital marker of diabetes control.

Through the MTIMA project, we are committed to developing primary care based solutions using innovative technologies to deal with the issue. We will build on the success of the EU FP7 Supporting LIFE project led by Dr O’Donoghue and Dr Gallagher currently running in the Mzuzu area, which uses an electronic decision support system on mobile phones to improve the management of illness in young children in Malawi.”

In Tumbuka, a Bantu language spoken in Malawi, Zambia and Tanzania, Mtima is the word for ‘heart’. It is a fitting title for the project given that the vast majority of complications in type 2 diabetes relate to cardiovascular disease and Malawi is known as the ‘warm heart of Africa’.

Further information on this project can be found at www.ghealthresearch.org
1 STOP HF study led by Prof Ken McDonald and Dr Mark Ledwidge, UCD, JAMA 2013

President of Ireland Young Researcher Award for UCD Scientist

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In recognition of his outstanding contribution to translational obesity research, Professor Carel le Roux (UCD Professor of Experimental Pathology) has received a President of Ireland Young Researcher award (PIYRA).

In recognition of his outstanding contribution to translational obesity research, Professor Carel le Roux (UCD Professor of Experimental Pathology) has received a President of Ireland Young Researcher award (PIYRA).

One of Science Foundation Ireland’s most prestigious accolades, this award acknowledges cutting-edge research in fields considered critical to Ireland’s economic and social prosperity.

President Michael D. Higgins said,

“This award recognises the ongoing contribution of Irish scientists to internationally respected research activity in areas of fundamental relevance to society and the economy.”

In an effort to address the increasing mortality and morbidity associated with obesity and its related diseases, Professor le Roux focuses on achieving a better mechanistic understanding of appetite control.

“If we can learn more about how the gut ‘talks’ to the brain to generate fullness, we can develop safer and more effective treatments for patients. The role of metabolic surgery, gut hormones, bile acids and changes in food preference are important areas of research focus in this quest”,

says Professor Carel le Roux, Professor of Experimental Pathology at UCD School of Medicine & Medical Science and Fellow of UCD Conway Institute.

“The immediate question for clinicians and surgeons is how to optimally use existing medical and surgical treatment to prevent or even reverse end-organ damage secondary to obesity or diabetes. By addressing this question, we can affect immediate health gain for patients and the health system.”

Professor le Roux said:

“Receiving the PIYRA has allowed me to expand our work and establish, within the UCD Diabetes Complications Research Centre, the first group in the world focusing on how changing the anatomy and physiology of the gut with surgery can be used to reverse organ damage such as diabetic kidney disease, which previously was thought of to be permanent. Improving our knowledge will facilitate health gain for patients while saving money for the health system.”

PIYRA is Science Foundation Ireland’s most esteemed award for researchers who have shown exceptional promise as possible future leaders in international research and are known for excellence in their fields. Awardees are selected on the basis of exceptional accomplishments in science and engineering and on the basis of creative research projects that have attracted international acclaim.

Commenting on the awards, Professor Mark Ferguson, Director General of Science Foundation Ireland and Chief Scientific Adviser to the Government of Ireland, said:

“PIYRA recognises outstanding researchers who, early in their careers, have already demonstrated or shown exceptional potential for leadership in their fields of research. Through this programme SFI is supporting a new generation of top-tier scientific researchers in Ireland.”

Professor le Roux received his award from President of Ireland Michael D. Higgins in Áras an Uachtaráin along with two recipients from Trinity College Dublin; Dr Matthew Campbell and Professor Valeria Nicolosi. Dr Campbell carries out research on eye conditions including age-related macular degeneration (AMD) while Professor Nicoloi researches materials that can potentially form the basis for innovative new technologies.