Scientists from Ireland and Germany have just discovered how certain immune cells in fat can collaborate to induce inflammation, which leads to weight gain and obesity. Their research identifies novel techniques to exploit the regulation of inflammation in adipose tissue, implying new approaches to obesity management (Wednesday 9th March 2022).
Obesity is on the rise in both adults and children around the world, with fat people being more likely to suffer diabetes, cardiovascular disease, and cancer. To address this problem, new therapies are required.
The scientists discovered how “checkpoint proteins” and immune cells change inflammatory cells within adipose tissue to create obesity in their study. These alterations in checkpoint expression in the visceral fat were predictive of the person’s weight in patients with obesity (Body Mass Index BMI> 30 kg/m²).
The researchers next demonstrated that changes in immune checkpoint proteins in mice fed a Western “high fat” diet were connected to large reductions in obesity and diabetes development.
Professor Padraic Fallon of Trinity College Dublin’s School of Medicine and Dr. Christian Schwartz, a former EMBO Fellow at Trinity and now a Principal Investigator at the University Hospital Erlangen led the study, which was recently published in the leading international biomedical journal Science Translational Medicine.
In our study, we analyzed the function of immune checkpoints on specific cells and it is 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.
Dr. Christian Schwartz
Prof. Fallon commented: “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 a severe disease that requires intensive care and also have an increased risk of mortality.”
Dr. Schwartz commented: “In our study, we analyzed the function of immune checkpoints on specific cells and it is 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.”
In collaboration with Dr. Andy Hogan (Maynooth University), Profs. Donal O’Shea and Helen Heneghan (St Vincent’s Hospital and University College Dublin), and Dr. Christian Krautz (University Hospital Erlangen), the study investigated inflammatory changes in patients with obesity, with or without type 2 diabetes (University Hospital Erlangen).
Science Foundation Ireland, the National Children’s Research Centre, the Interdisciplinary Center for Clinical Research, the University Hospital of Erlangen-Nüremberg, and the Else Kröner? Fresenius? Stiftung supported the research. Dr. Schwartz was a visiting fellow at the EMBO for a long time. Dr. Heike Hawerkamp is a Fellow of the Irish Research Council.
