Immune system plays major role in regulation of body weight

New research involving a team of Irish, American and Canadian researchers reveals that the immune system could be responsible for as much as 40% of our body’s ability to regulate weight.

According to Prof Donal O’ Shea, Consultant Endocrinologist at St Vincent’s University Hospital and the Conway Institute at University College Dublin, and one of the lead authors on the research paper,

‘We know that once weight is gained, for the majority of people, it is very difficult to lose that weight. It is too simplistic to say eat less, move more and the weight will come off. It doesn’t actually work like that. The body has a very powerful reaction to defend against weight loss, which we now know involves the immune system. 

We normally think of the immune system as something that guards against infection and diseases. However in evolutionary terms, a sudden or rapid weight loss could be a more immediate threat to survival. This immune system response contributes to why people really struggle to lose weight, despite their best efforts to control calories and do exercise. Our findings give us a much better understanding of why this is so and they illustrate the dynamic role that the immune system plays in regulating body weight'.

Dr Lydia Lynch, Assistant Professor, Harvard Medical School, and Associate Professor, Trinity College Dublin, and the lead author on the study takes up the story. 

‘We discovered that a very common immune cell, called the invariant natural killer T cell (iNKT cell), often described as the Swiss army knife of the immune system because it does so many jobs, plays a key role in setting off a complex chain of events that regulate and enhance weight loss.

The iNKT cell is needed to help fat cells make a small protein called fibroblast growth factor-21, (FGF-21) which triggers the body to metabolise or turn white fat into a much healthier brown fat. This browning of white fat uses large amounts of energy, leading to increased metabolic rate and weight loss. 

We know that people who are obese often have sluggish immune systems and a lower amount of these iNKT cells. With less iNKT cells, the body doesn’t make FGF-21, and this prevents the body from converting white fat to change it into brown fat. So, if you stimulate the body to produce iNKT cells, you can increase the amount of FGF-21. This, in turn, leads to enhanced browning of white fat, and increased metabolic rate and weight loss.

This new knowledge opens up novel areas for treating weight loss, and will greatly enhance our ability to improve existing hormone treatments for weight loss'.

Brendan Quinn is a fitness instructor who became obese after he developed an immune system disorder. With no change in his diet and exercise levels, his weight went from 76kg to 120 kg over a three-to-four year period.

‘I was really struggling to try to lose the weight.  I was very strict with my diet and exercise, and in theory I should have been losing weight, but it just wasn’t coming off. When Professor O’Shea approached me, I was very happy to try this new approach which tried to get my immune system to work better in order to then allow my body to lose weight. The results were almost immediate. I lost 12 kg in the first five weeks, and a total of 23 kg since I started treatment five months ago’. 

Graham Love, Chief Executive of the Health Research Board, who funded the Irish arm of the research comments,

‘This is a highly significant breakthrough in understanding obesity, one of the global health challenges of our time. It will help change approaches we take to care and transform many people’s lives’.

Professor O’Shea adds,

‘These findings represent a significant step forward in our understanding of why people often find it so hard to lose weight, despite their best efforts. The findings should help break many of the stigmas associated with obesity, and most importantly, they could dramatically improve outcomes for patients.

Ultimately, this research underlies the absolute importance of prevention of weight gain in the first place. This work should be used by policy makers to prioritise obesity prevention strategies, especially childhood obesity’.

The research has just been published in the journal Cell Metabolism and is available from their website at the link below.

The research was funded by the Health Research Board in Ireland, the European Research Council and the National Institutes of Health, USA.  


For further information please contact Brian Cummins, e, t +353 1 2345136, m +00353838879313.

Notes for Editors:

The Health Research Board is the lead agency in Ireland supporting and funding health research. Our mission is to improve people’s health and to enhance healthcare delivery. We will lead and support excellent research, we will generate relevant knowledge and promote its applications in policy and practice.

The European Research Council’s (ERC) mission is to encourage the highest quality research in Europe through competitive funding and to support investigator-driven frontier research across all fields, on the basis of scientific excellence.

The National Institutes of Health (NIH) is one of the world's foremost medical research centers, and the Federal focal point for medical research in the United States. The NIH, comprising 27 separate Institutes and Centers, is one of eight health agencies of the Public Health Service which, in turn, is part of the U.S. Department of Health and Human Services. The goal of NIH research is to acquire new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold. The NIH mission is to uncover new knowledge that will lead to better health for everyone.