Role of inhibitor of kappa B kinase epsilon in sex-dependent differences in metaflammation

Type 2 diabetes, non-alcoholic fatty liver diseases, cardiovascular diseases and certain cancers are all diseases of deregulated metabolism and are linked to obesity. With our failure to combat the worldwide rise in obesity, there is now an urgent need to develop therapeutic approaches that can uncouple obesity from the development of these devastating diseases. This requires a better understanding of the biological processes that promote or prevent the development of metabolic disease.

My previous studies have investigated the involvement of low-level activation of the immune system in reprogramming metabolism. I have identified new signaling proteins, such as IKBKE, that regulate the inflammatory responses to metabolic stress. However, female sex hormones (or oestrogens) can also dampen inflammation and pre-menopausal women appear to be protected from developing obesity-related metabolic diseases. To date, very little is known about how this protection occurs. I will study how oestrogens interact with IKBKE and the immune system’s ability to respond to metabolic stress.

The knowledge gained from this study will improve our understanding of the biological processes that can be used to protect people with obesity from developing metabolic diseases. We will also shed light on the immuno-metabolic changes that may accompany menopause.