Can we protect against high levels of stress hormones that cause heart disease?

Adipose glucocorticoid exposure is regulated by proteolytic cleavage of corticosteroid binding globulin (CBG)

High levels of stress hormones, called glucocorticoids, are known to cause obesity, diabetes and heart and circulatory diseases. The hormones circulate in the blood bound to another molecule called corticosteroid binding globulin (CBG), which controls their activity. Glucocorticoids have important functions in fat tissue, but we do not fully understand how CBG controls how the hormones reach the fat tissue to carry out their actions. Dr Nixon’s previous work has shown that a molecule called neutrophil elastase can cut CBG into pieces, which releases the glucocorticoid hormone. In this fellowship, he will build on this research by studying how neutrophil elastase affects levels of the hormones in fat and how this is linked to healthy metabolism. He first hopes to determine whether fat cells produce CBG, or whether it moves from the circulation into the fat tissue when required. This will establish whether CBG in fat cells serves as a protective mechanism against the hormones, and whether being cleaved by neutrophil elastase overrides this protection by releasing the hormones into fat tissue. He will also investigate whether chemicals that block neutrophil elastase can prevent the release of the hormones, and whether this occurs throughout the body or only in fat tissue. The results will provide important insights into whether blocking neutrophil elastase has therapeutic potential for treating metabolic conditions like obesity and preventing heart disease.