LTB4 molecule could explain link between obesity and type 2 diabetes

Wed, 25 Feb 2015
The molecule LTB4 may be able to explain the link between obesity and type 2 diabetes, potentially opening up new therapeutic possibilities.

It is well known that obesity causes inflammation, which causes type 2 diabetes. Why inflammation causes type 2 diabetes, has long been a mystery. A new study, conducted at UC San Diego School of Medicine and published in Nature Medicine, may have found the answer.

How was the study conducted?

The researchers discovered that LTB4, an inflammatory molecule, triggers insulin resistance, which is one of the biggest factors in the development of type 2 diabetes.

The study was conducted on obese mice. When the researchers genetically removed the cell receptor that responds to LTB4 - or used drugs to block it - the insulin sensitivity of the obese mice increased.

Why does LTB4 cause insulin resistance?

Extra fat triggers macrophages, which are immune cells. When macrophages are triggered, they release LTB4. The problem is, LTB4 activates more macrophages, which then release more LTB4.

This cycle is problematic. As more macrophages are triggered, more LTB4 is released, which affects more cell receptors. All of these affected cell receptors develop insulin resistance.

The study suggests that obesity is linked to type 2 diabetes because it causes excess LTB4 production, which, in turn, causes more inflammation, which causes more insulin resistance.

Insulin resistance is one of the major factors of type 2 diabetes.

What can be done about it?

When the researchers discovered the inflammation mechanism in obese mice, they genetically engineered mice that did not have the LTB4 receptor. These mice had much better metabolic health than those with LTB4.

Then the researchers tried to block the LTB4 receptor with a molecule inhibitor, and found it just as effective a way of inhibiting insulin resistance.

These results suggest that new therapeutic approaches may be possible in the near future. Perhaps addressing the proliferation of LTB4 could provide a solution for type 2 diabetes.

The significance of the findings

"The study is important because it reveals a root cause of type 2 diabetes," said Professor Jerrold Olefsky, senior author of the study. "And now that we understand that LTB4 is the inflammatory factor causing insulin resistance, we can inhibit it to break the link between obesity and diabetes.

"We disrupted the LTB4-induced inflammation cycle either through genetics or a drug, it had a beautiful effect - we saw improved metabolism and insulin sensitivity in our mice.

"Even though they were still obese, they were in much better shape."
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