By Ann Liu, PhD
Historically, immunology and metabolism have been distinct disciplines. However in recent decades we have learned that metabolic diseases such as obesity and type 2 diabetes result in major changes in inflammation and the immune response. Conversely, it has also become clear that certain behaviors and properties of lymphocytes are regulated by internal metabolic processes. Thus the new field of immunometabolism has emerged to examine the crosstalk between immune and metabolic processes. Speakers at the symposium “Diet and Immunometabolism,” co-sponsored by the Nutritional Immunology and Obesity RIS, highlighted the role of nutrients and metabolites in inflammatory processes on March 31.
While we may traditionally think of iron’s role in anemia and fetal development, it is also required for proper immune function and adipogenesis. Elevated serum ferritin levels are associated with type 2 diabetes, gestational diabetes, and metabolic syndrome. Excess iron also induces lipolysis and insulin resistance. Dr. Alyssa Hasty from Vanderbilt University School of Medicine presented data from mouse models indicating that iron homeostasis is disrupted during obesity. Iron is traditionally stored in the liver, however during obesity it appears that iron levels decrease in the liver and increase in adipocytes.
These changes may be related to changes in macrophage populations, which are important mediators of adipose tissue inflammation. Hasty identified two distinct macrophage populations based on their iron content. Some macrophages have high iron content which allows them to be isolated using a magnet while others have low iron content. Lean animals have both types of macrophages. However obese animals have increased levels of macrophages with low iron content.
This indicates that iron levels are changing in both adipocyte and macrophage populations during obesity and suggests that the ability of macrophages to sequester iron may be impaired. Further study is needed to identify the mechanisms of crosstalk between macrophages and adipocytes and examine potential functional consequences.