According to the report published in Immunity, by Marie Curie Fellow and Lydia Lynch from Trinity College, Dublin Ireland, along with experts from Beth Israel Deaconess Medical Centre and St Vincent's University Hospital, invariant natural killer T-cells (iNKT), immune cells that fight malignancy, disappear when humans become overweight, but can be restored after losing weight.
The authors have determined that treatments to jumpstart iNKT cells can help to keep weight off and control diabetes and metabolic diseases. Previously, iNKT were thought to be found infrequently in humans, however, the recent study has discovered that there are a great number of them found in omental fat in humans.
Dr Lynch, one of the authors of the study, said :
"We then found a large population of iNKT cells in fat tissue from mice. Now we have identified a role for these cells in the regulation of body weight and the metabolic state likely by regulating inflammation in adipose tissue."
In addition to these findings, they also found that a lipid named alpha-galactosylceramide (aGC) can greatly impact weight loss, fatty liver disease, metabolism, and can reverse diabetes by strengthening cells that are damaged.
The study began in 2007, when Dr Lynch teamed up with Professor Donal O'Shea at the Obesity Clinic at St Vincent's University Hospital in Dublin where she made obese people's immune systems the center of her attention. All of the data on the humans came from Irish patients, and was moved to Boston.
She said: "We knew that not only did obese patients have more heart attacks and a greater incidence of type 2 diabetes than lean individuals, but they also developed more infections than non-obese individuals."
Each patient had their blood taken, revealing that iNKT cells, as well at NKT cells, were lowered and when fat tissue was studied among a group of obese people. Patients who had dropped weight after bariatric surgery showed an increase in iNKY cells, bringing them to normal levels.
During the new trial, the experts conducted a number of experiments on animals in order to determine if their theories about iNKT affecting fat tissue regulation were correct.
Other studies, by Professor Mark Exley and Cliona O'Farrelly, had reported large numbers of iNKT cells found in human and mouse liver tissue. Therefore, the experts wanted to prove that mice also harboured these cells in fat.
When they found a great deal of iNKT cells, the team put the mice on a diet rich in high-fat, and analyzed the results.
"We found load of them", said Dr. Lynch. "We actually reversed the diabetes, and even though the mice continued to eat a high fat diet, they lost one to two grams of weight (normal mouse weight being 20 to 25grams, and exhibited a host of features that suggested reduced inflammation, including improved insulin sensitivity, lower triglycerides and leptin, and shrunken adipocytes.
Similar to the human subjects we had previously studied, the animals lost their iNKT cells when they became obese. Once we took them off this diet and put them back on a normal standard-fat diet, they lost the weight - and their iNKT cells increased."
For their next investigation, the team wanted to find out the role of iNKT cells by analyzing two different kinds of mice, both which had a lack of iNKT cells, and one group of control mice, all on high-fat diets.
The authors then removed the iNKT in the normal mice and put them into the NKT-deficient mice.
To determine whether the iNKT cells that were left over in obesity could be activated to benefit metabolism, the experts tested aGC, which is a lipid capable of activating iNKT cells.
Giving just one dose of aGC resulted in a significant advance in fatty liver diseae and metabolism, dramatic weight loss, and diabetes reversal.
Exley continued: "aGC has been tested in clinical trials for the treatment of certain cancers, including melanoma, and proven safe and produced few side effects in humans. The effect of NKT stimulation, whether by aGC or other means, on weight loss, obesity, and metabolic disorder has not been investigated until now and may provide a new avenue for the treatment of obesity and metabolic syndrome, which have now reached epidemic proportions worldwide."
Written by Christine Kearney