Alexaki Lab - Neuroinflammation

 Research Focus

Our work explores the reprograming of cell metabolism in metabolic disease in different tissues. We aim to understand which metabolic adaptations are protective and which are maladaptive and identify key metabolic components that can be targeted to normalize tissue physiology.

Diet-induced obesity is a very common metabolic disease with detrimental consequences such as cardiovascular disease, liver disease, cancer, and depression. Although initially affecting the adipose tissue, which acts protectively by storing excess lipids due its enormous expandability, obesity gradually has systemic consequences. The current view is that this is due to inflammatory and metabolic spill-over from the hypertrophic adipose tissue to the circulation, which affects other organs. Our aim is to better understand the pathways involved in these processes.

We recently found that polyamine metabolism is key in preserving adipose tissue health, as it inhibits its hypertrophy and inflammation. Obesity is often linked to chronically increased circulating amounts of glucocorticoids, which if chronically elevated, promote insulin resistance, central obesity and neurodegeneration.

We study the mechanisms underlying chronically increased glucocorticoid production and the consequences thereof. In this context, we examine the effects of chronically elevated glucocorticoids in microglia, the counterparts of macrophages in the brain. Furthermore, we study the immunometabolic circuitry underlying acute and chronic microglia activation.  

 Specific expertise

• Macrophage and microglia-mediated inflammation
• Cellular metabolism (citrate cycle, arginine metabolism, lipid metabolism)
• Adrenal hormones
• Inflammatory mouse models