Fat fighter

CAN AN immune cell found in fat tissue and blood protect against obesity and its related ills? And could it even help to reverse them?

Those are the intriguing suggestions from a new study involving Irish researchers and patients.

The research found that both humans and mice lose a type of immune cell called an invariant natural killer T (iNKT) cell in obesity, but – in mice at least – bumping the cells back up again resulted in weight loss and better metabolic health, even though they continued to eat a high-fat diet.

The findings shed more light on the links between obesity and the immune system, explains researcher Dr Lydia Lynch, a Marie Curie research fellow at Harvard Medical School and Trinity College Dublin.

“Obesity and its related diseases threaten to shorten the lifespan by five to 20 years, and much of this is due to inflammation,” she explains. “Inflammation in fat – in other words when immune cells infiltrate fat and become active – is now known to play a major role in development of insulin resistance and diabetes, directly linking the immune system and obesity and metabolism.”

Lynch and her colleagues became interested in iNKT cells because they are sensitive to lipids. Until recently, these immune cells had been thought to be rare in humans, but Lynch found enriched populations of them in fat tissue in lean humans. And she saw that the numbers of iNKT cells seem to fall away in obesity.

The new study, published in Immunity, went further and worked out that when obese humans lost excess weight, their levels of iNKT cells went up. But humans aren’t always the most practical of models to study in the lab, so the researchers turned to mice.

The study found that the animals also have plenty of iNKT cells in their fat tissue, and again the numbers plummet in obesity, suggesting there are parallels between mouse and human when it comes to iNKT cells and fat. And their new experiments suggest that iNKT cells are not just passive bystanders in obesity and its fallout. Instead, they seem to be protective.

“We wondered what would happen if there were no iNKT cells and you became obese, so we looked to mice models that had no iNKT cells,” says Lynch. “When these iNKT-knockout mice ate a high-fat diet, they became fatter and developed insulin resistance, and they had more inflammation in their fat compared to normal mice eating a high-fat diet.”

And what really sealed the deal was that introducing iNKT cells to the obese mice seemed to transform them. “We then put iNKT cells back into these obese knockout mice and found that even though the mice still ate a high-fat diet, they lost weight and their diabetes went away,” says Lynch.