Obesity can be controlled by blocking DHPS enzyme to treat systemic Inflammation: Study

A recent finding at the University of Chicago & Indiana University has revealed that a protein called elF5A is responsible for triggering inflammation in macrophage cells in a person suffering from obesity. The experimental study was carried on mice and it was found that blocking DHPS enzyme eIF5A protein can be modified, resulting in reduced inflammation, improved glucose control, and low obesity. The experimental study was published in the journal Cell Metabolism. The findings claim that DHPS is a conserved protein that is present in many animal species, bacteria, and humans, and it has mostly been studied in yeast and other cultured cells. 

According to a senior researcher, Emily Anderson Baucum, who is a former post-doctoral scholar at Indiana University:

"When I joined the lab as a postdoc, I was interested in seeing if the DHS pathway could be a common thread promoting inflammation both in the pancreas, as Dr. Mirmira's lab had shown, and in the setting of adipose tissue meta-inflammation."

The researcher found that the effects on the e1F5A protein, which DHPS activates by modifying lysine amino acids to generate a rare amino acid called hypusine. It was found that if eIF5A gets activated, it creates an impact on mRNA translation that affects processes like apoptosis, cell proliferation, and differentiation. Notably, eIF5A gets converted into mRNAs which are associated with inflammation. The translation of mRNAs determines which proteins are expressed within a cell, and in turn, how that cell functions.

Study claims that obesity can be controlled by blocking DHPS 

Another researcher who is also a professor at UChicago Medicine, Mirmira, claimed that:

"EIF5A is important in the production of other proteins because of its effect on mRNA translation, but it only does this when cells are under stress. This is often protective, but a protective process can become destructive if the stress is high enough and can eventually kill the cell. Obesity is an example of an environment that tends to put a lot of stress on our cells, which can trigger these inflammatory pathways that normally would be triggered. So, we wanted to determine what role these two proteins play in obesity, and in particular, in the macrophages, cells that we know play a role in inflammation in obesity."

It was found during the research that those mice who were obese, had an increased level of DHPS, and eLF5A--eIF5Hyp was enriched in macrophages found in adipose tissue. Macrophages are a type of WBC that plays a vital role in the immune system by removing dead cells in the body, increased expression of eIF5AHyp led to an increase in the number of inflammatory macrophages. The researchers observed that after blocking DHPS in mice, it was found that the way macrophages behaved could be changed, and they did not function in an inflammatory mode anymore. Although the animals accumulated fat, however, they did not show any metabolic dysfunction and they didn't get hyperglycemia. It was also found that blocking the DHPS caused an overall reduction in mRNA translation in inflammatory macrophages and a reduction in the secretion of some proteins associated with inflammation.

Researchers observation

The researchers observed that macrophages played a crucial part in the development of the inflammation seen in obesity and that addressing this inflammation can be useful in treating obesity and its complications, and a single enzyme could be important in the way that macrophages behave. The researchers further claimed that developing a small molecule to block DHPS could be a direct option for the treatment of inflammation. Moreover, many other factors are involved, including environmental and genetic factors, along with lifestyle and diet.
 

(IMAGE: Unsplash)
(With Inputs from ANI)