This issue includes a new perspective on obesity. While we know that obesity is a major health issue, the subject seems removed from the usual emphasis on immunology and neuroimmunology that appears in this publication. But the theme of the obesity paper is inflammation, and the latter is not far afield at all. Inflammation is a player in most areas of medicine, especially the brain, as it relates to multiple sclerosis, cancer, injury, and degenerative disease.
Classically, inflammation comprises two sets of changes. One is an influx of white cells from the blood into a tissue, and the second are blood vessel changes that allow fluids and white cells to enter.
Generally, inflammation occurs when tissues are injured or wounded, or when they are attacked by infection. In these situations, inflammation is helpful and protective. But components of inflammation are now turning up in places where no injury or infection is apparent, and contributing to diseases like obesity, atherosclerosis, cancer, and autoimmune diseases including multiple sclerosis.
A major driver for this wide reach of inflammation is a cell type called the macrophage. Macrophages enter sites of wounding, injury, and infection, and play major roles in the healing and defense processes. But macrophages also can be activated in detrimental ways in all the diseases mentioned above, including obesity.
The paper in “Science Translational Medicine” from Kishore et al describes the discovery that a fatty meal is being detected by macrophages. Usually fat, liver, and muscle cells are the focus of research in this area, but inflammatory cells like macrophages also make important decisions on the basis of the dietary fat they encounter.
The macrophage response to fatty acids, uncovered by Kishore et al, is to produce plasminogen activator inhibitor-1 as well as other major inflammation-associated proteins, tumor necrosis factor and interleukin-1. This inappropriate stimulation of macrophages, here by elevated fatty acids, contributes to the major consequences of obesity, like diabetes.
Macrophages also are normally found in all tissues. They are particularly abundant in the brain, where they are called microglia. For decades, macrophages have been considered the “versatile elements of inflammation.” Over time, scientists recognized more and more examples of this versatility. This includes ways in which macrophages inappropriately make inflammatory products, with high fatty acids being a new trigger. But don’t forget, macrophages and inflammation also are valuable in protection and in homeostasis, returning the body to normal when perturbed.
An impressive feature of the research of Kishore et al is that their discoveries were made through studies of human subjects. Such studies do not merely extend what we already know in simpler systems. Instead, research on human subjects uncovers totally new perspectives.