Metabolic challenges of immune cells in obesity, diabetes, and cardiovascular disease

Research interests

Although inflammation is a vital response to infection and tissue injury, non-resolved chronic inflammation is associated with many pathological processes. Several of these pathologies, in which inflammation is a common denominator, are grouped under the term of “metabolic syndrome”, including obesity, type 2 diabetes (T2D), and cardiovascular disease. Over the past two decades, a clear link has been established between obesity-associated inflammation and the development of insulin resistance (IR), which eventually leads to T2D. Obesity-induced adipose tissue (AT) inflammation is largely the result of a shift in the balance of anti-inflammatory towards pro-inflammatory immune cells. Likewise, atherosclerosis is also associated with a chronic and non-resolving immune response. The accumulation of lipoproteins in the arterial wall, characteristic of atherosclerosis, triggers first an innate immune response, dominated by monocyte/macrophages, followed by an adaptive immune response involving primarily Th1, but also Th17 and Th2 cells and B cells, alongside a progressive decrease in Tregs.

It was shown over the years that immune cells can adapt their metabolism to support the bio energetically demanding processes of growth and effector function during an immune response. Furthermore, it was demonstrated that by directly manipulating cell metabolism one can regulate immune cell fate; for example, inhibition of glycolysis blocks Th17 development and promotes T cell polarization towards Treg cells. Similarly, anti-inflammatory M2 macrophages depend on fatty acid oxidation for their metabolic needs while pro-inflammatory M1 macrophages use glycolysis.

The research objectives of our team are to characterize the metabolic needs of immune cells (i.e. monocytes/macrophages and T cells) in obesity, diabetes, and cardiovascular disease with the long-term goal to develop strategies to manipulate immune cell metabolism as a novel therapeutic approach to prevent/treat these pathologies.

Team Publications