Irish and German scientists have identified a new immune process involving inflammation which could lead to new ways of managing obesity.

Obesity is a serious public health issue worldwide and those affected face an increased risk of developing diabetes, cardiovascular disease and some forms of cancer. New therapies to tackle this issue are needed.

The scientists have managed to identify how specific immune cells can work together in fat to cause inflammation that leads to weight gain and obesity.

They identified how “checkpoint proteins” and immune cells alter inflammatory cells within the fat tissue to cause obesity. In people with obesity, i.e. those with a BMI> 30 kg/m², these changes in checkpoint expression in the visceral fat were predictive of the person’s weight. 

The scientists then showed that modifications in the so-called immune checkpoint proteins of mice on a Western high fat diet were linked to dramatic reductions in the development of obesity and diabetes. 

The study was led by Prof Padraic Fallon from Trinity College Dublin’s School of Medicine and Dr Christian Schwartz, a principal investigator at the University Hospital Erlangen, Germany.

According to Prof Fallon, this new process of checkpoint regulation of cells in visceral fat of obese individuals “advances our understanding of how the immune system controls diet-induced weight gain that can lead to conditions such as obesity and type 2 diabetes”.

“Our discovery has broader impacts on addressing how obesity influences co-morbidity with other diseases, as shown in the Covid-19 pandemic where obese individuals that are infected with SARS-CoV-2 are more likely to develop severe disease that requires intensive care and also have an increased risk of mortality,” he said.

According to Dr Schwartz, this study analysed the function of immune checkpoints on specific cells and it was “fascinating to see that a small change on one of many cell populations in the fat has such an impact on the outcome of the disease”.

“Only through our basic research efforts using pre-clinical models were we able to gain access to patients’ samples and link our findings to human disease. It will be interesting to investigate now how we can manipulate this checkpoint on specific cell populations of interest to help people with obesity,” he noted.

The study investigated inflammatory changes in patients with obesity, with or without type 2 diabetes, in collaboration with Dr Andy Hogan of Maynooth University, Prof Donal O'Shea and Prof Helen Heneghan of St Vincent's Hospital and University College Dublin, and Dr Christian Krautz of University Hospital Erlangen. 

The study is published in the journal, Science Translational Medicine.