A potential therapeutic target for curbing inflammation in obese people has been identified byresearchers from University of California, San Diego.
The new evidence would help explain how saturated fatty acids, which soar in those who are obese, can lead the immune system to respond in ways that add up to chronic, low-grade inflammation.
AdvertisementIt would open up new avenues for developing treatments to curb that inflammatory state, and the insulin resistance and type 2 diabetes that come with it.
One key is an immune receptor (called Toll-like receptor 4 or Tlr4) at the surface of blood cells, including a particularly "angry" class of macrophages known to pump out toxic molecules and spur inflammation. It now appears that fatty acids may in essence "hijack" those immune cells via Tlr4.
"Tlr4 is out there to sense bacterial products, but one of those looks a lot like fatty acids," said the study's senior author Jerrold Olefsky of the University of California, San Diego.
"They don't know it's not bacteria," Olefsky added.
Scientists had suspected that Tlrs might be the "sensors" linking obesity to inflammation.
In the new study, the researchers show that this interaction is particularly important in the bloodstream. Mice lacking Tlr4 only in blood cells grew obese when they were fed a high-fat diet, but they were largely spared the metabolic consequences of their obesity.
The mice were fat, but metabolically they continued to "look pretty normal," Olefsky added.
"A Tlr4 antagonist - now that's a therapeutic. The jury is still out, but it sure makes sense they could be a new class of insulin sensitizers," Olefsky said.
The researchers said that drugs aimed at Tlr4 have already been developed, and the idea that those drugs may hold promise in fighting insulin resistance and type 2 diabetes is one Olefsky's team is now exploring in detail in the mice.
The study appears in Cell Metabolism, a Cell Press publication.