Posted on June 15, 2015

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

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