Tweaks to immune checkpoint proteins apply brakes to obesity
Research continues to uncover the role that inflammation plays in obesity and the development of related conditions, and a new study has shed yet more light on the issue. Scientists have found that modifying so-called "checkpoint proteins" in the immune system can regulate inflammation in fat tissue, with the result being significant reductions in obesity and diabetes in pre-clinical models.
The breakthrough was made by scientists at Germany's University Hospital Erlangen and Ireland's Trinity College Dublin, and involves a protein called programmed death-ligand 1, or PD-L1. This protein acts as a type of "brake" that helps regulate the body's immune response, and for this reason it has come to play a critical role in the field of immunotherapy treatments for cancer.
PD-L1 has the capacity to bind to receptors on all-important T-cells, which prevents these killer immune cells from taking out dangerous cells containing the PD-L1 molecule, which can include cancerous cells. Anti-cancer drugs called checkpoint inhibitors are designed to bind to PD-L1 and block this action, in turn releasing the brakes and allowing the killer T cells to go to work.
The authors of this new study sought to learn more about the role of PD-L1 in immune system regulation with respect to obesity, and how it causes inflammation in fat tissue to drive the condition. Through experiments on mice, the scientists were first able to show how modifying the PD-L1 protein on key immune cells altered the inflammatory cells within fat tissue.
The result of these tweaks in mouse models of diet-induced obesity, which were fed a Western-style "high-fat" diet, were dramatic reductions in the development of obesity and diabetes. Through analysis of obese human samples, the team was also able to show that these changes in expression of checkpoint proteins correlated with the person's weight.
“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," said study author Dr Christian Schwartz.
By discovering this mechanism, the scientists hope with further research they can develop new ways to manage obesity and its deleterious effects, such as diabetes, cancer and cardiovascular 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," Schwartz said. "It will be interesting to investigate now how we can manipulate this checkpoint on specific cell populations of interest to help people with obesity.”
The research was published in the journal Science Translational Medicine.
Source: Trinity College London via EurekAlert