New study identifies mediators of obesity related inflammation

Study shows mediators in inflammation associated with obesity. Source: Nick Youngson (via
Researchers have pinpointed the responsible cell type for triggering inflammation in obesity and related inflammatory mediators in a new study.

By Mili Jayadeep | Science Editor

Obesity, a condition of high body weight and high body fat content, affects 1 in 4 adults in the UK. It is associated with the instigation of serious chronic conditions such as type 2 diabetes, coronary heart disease, cancers and stroke.

When someone consumes more calories than energy expended, the body stores these in the form of molecules known as triglycerides inside fat/adipose tissue, which is known as white adipose tissue (WAT). In people who are obese, overworking of WAT results in fat cell death triggering the immune response. It is theorised that signalling molecules in WAT may be responsible for this immune response but the exact mechanisms of inflammation is not well researched. 

 UT Southwestern researchers have pinpointed the responsible cell type for triggering inflammation in mice adipose tissue. Rana Gupta, the study lead, associate Professor of Internal medicine says, 

 “By identifying these cells, we’ve taken a step toward understanding some of the initial events that contribute to that inflammation.”

The scientists focussed their research efforts on the blood vessels, inflammatory molecules and immune cells associated with WAT. In 2018, the team identified cells lining these blood vessels known as adipose progenitor cells (APC) that have involvement in mediating inflammation.

Studying the effects of this molecules in mice models revealed that swapping the mice to a high fat diet caused an increase in these inflammatory mediators which contribute to increased inflammation. In obese people, this would translate to increased inflammatory processes caused by these particular molecules. Gupta says,

 “This is the first study to demonstrate that these cells play a very active, early role in being gatekeepers of inflammation in fat tissue,” 

The researchers also found that the involvement of an immune signalling gene, Tlr4 is a potential target for disrupting this pathway hence hindering the inflammatory processes. They demonstrated this by conducting research as mice without the Tlr4 gene given a high fat diet gained as much unhealthy weight accompanied by inflammatory changes as the mice in their previous model experiment. Whereas when the mice were genetically engineered, the mice showed low levels of inflammation similar to mice on a low fat diet. This could be explained by the phenomenon that the genetic correction prevented the signals associated with increasing inflammation associated with weight gain. A similar signalling molecule known as ZFP423 also has a role in contributing to inflammatory processes. Gupta explains,

 “It looks like ZFP423 could be an important brake in terms of slowing the inflammatory signals in these cells,”  

This new study is the first one to demonstrate the role of these cells in the inflammatory pathway, published in the journal, Nature Metabolism. This study’s findings introduces new possibilities of treatment for targeting obesity and potentially prevent the associated diseases that can develop. Despite these exciting findings, Gupta cautions: “Of course, it remains to be seen if that’s true in humans as well as mice.”

The future directions of the study includes investigating these processes in human fat cells. Mice make excellent animal models due their similarities to the human genome hence providing experimental results predictive of that observed in humans. Therefore, the study shows great promise for the future in discovering new ways of treating obesity and related diseases and potentially halting inflammation associated with obesity. However, it is only through work on human cells that the true implications of these findings will be seen. 

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