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A new review from the Domingos Lab, authored by Chelsea Larabee, Oliver Neeley and Ana Domingos, examines the intersection between neuroimmunology and immunometabolism, and in doing so reveals the existence of an exciting new area of study.

The Domingos Group investigate critically specific areas within neuroimmunology and immunometabolism. Within the former, the team studies the immune cells that interact with the sympathetic nerves within fat, which they have demonstrated to directly control adiposity. Within the latter discipline, they look at the function of immune cells in whole body metabolism and how it can lead to obesity. What is less commonly researched, however, is the point at which these two fields intersect:

Neuroimmunology and immunometabolism are burgeoning topics of study, but the intersection of these two fields is scarcely considered. This interplay is particularly prevalent within adipose tissue, where immune cells and the sympathetic nervous system (SNS) have an important role in metabolic homeostasis and pathology, namely in obesity. - Chelsea M. Larabee et al

In a new review published in Nature Reviews Endocrinology, Domingos Lab researchers consider the three main players at the forefront of this intersection - fat cells, immune cells and the sympathetic neurons that talk to fat. It is now well-known that immune cells play a significant role in obesity and that there is extensive crosstalk between fat cells and immune cells, comprising the study of immunometabolism. Furthermore, in a 2015 paper published in Cell, the team clearly established that the sympathetic nervous system is also important in obesity. This study was followed up by a 2017 paper published in Nature Medicine, in which the team demonstrated that immune cells referee how sympathetic neurons and fat cells interact, broadly fitting into the category of neuroimmunology (which studies the interaction of neurons and immune cells). Significantly, this neuroimmunological interaction directly regulates adipose tissue and effectively merges with immunometabolism, a field which examines the roles for immune cells in metabolism.

 

Our finding doesn't fit completely into either of these fields. These three players all work together and should all be considered when approaching the study of obesity - constituting neuroimmunometabolism
- Dr Larabee

The team were able to see that the two existing fields cannot fully explain the conclusions of these results. Consequently, they have defined a new field of Neuroimmunometabolism. In doing so, the perspective of metabolism research is broadened to take all three main players into account. Neuroimmunometabolism is the study of interactions between immune cells, neurons, and metabolic cells (such as fat cells) that affect whole-body metabolic state.

 

Our groundbreaking 2017 Nature Medicine paper is the cornerstone of this. It had previously never been shown that immune cells could modulate communication between neurons and fat cells to affect obesity.  - Dr Larabee

The team's 2017 paper, alongside two other significant papers of that same year referenced within their review, report on a type of immune cell called macrophages within fat tissue that affect how sympathetic nerves talk to fat cells – fitting into the newly defined category of “neuroimmunometabolism”. However, in order to call this a field, researchers must expect for these findings to broadly expand outside of these three specific players.

 

We do indeed anticipate that this field will grow. For example, other immune cell types besides macrophages likely play an important role. The same immunocyte-sympathetic neuron interaction could also be happening in other organs, such as the pancreas, liver, gut, thyroid, etc, which also affect metabolism. Moreover, besides sympathetic neurons, organs also communicate with parasympathetic neurons (that tend to control organs in the opposite way of sympathetic) and with sensory neurons, which report information from the organ back to the brain - communication with these other two types of neurons could also be affected by immune cells. These are all hypothetical, but I venture to say are very likely. Something very similar happened in 2003 when macrophages were first discovered in fat tissue - this one finding exploded and there have since been many follow-up studies, which initiated the field of immunometabolism that we discuss in our review. - Dr Larabee

The full review "Obesity: a neuroimmunometabolic perspective" is available to read in Nature Reviews Endocrinology.

 

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