KING’S COLLEGE LONDON (UK) — Researchers are hopeful that obesity can be “uncoupled” from insulin resistance after finding that the immune system and a key protein link the two disorders.
There are an estimated 371 million people with diabetes in the world and around 90 percent of these cases are type 2 diabetes. By 2030, there will be some 550 million with the condition based on current trends.
Cases of diabetes have more than doubled since 1980, with 70 percent of the trend due to aging populations worldwide and the other 30 percent estimated to be due to increasing prevalence of risk factors including obesity.
New research published in Cell Metabolism identifies a key mechanism in the immune system involved in the development of obesity-linked type 2 diabetes. The findings open up new possibilities for treatment and prevention of this condition, which is becoming increasingly prevalent worldwide.
The association between obesity and diabetes has long been recognized but the molecules responsible for this association are unclear.
Lead author Jane Howard and her colleagues from King’s College London studied mice genetically engineered to lack T-bet, a protein that regulates the differentiation and function of immune cells. They found that the mice had improved insulin sensitivity despite being obese.
“When T-bet was absent this altered the relationship between fat and insulin resistance; the mice had more intra-abdominal fat but were actually more sensitive to the glucose lowering effects of insulin,” says Howard. “As fat accumulation in the abdomen is typically associated with worsening insulin resistance and other features of the metabolic syndrome, the findings seen were both unusual and unexpected.”
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It turned out that the intra-abdominal fat of these mice contained fewer immune cells and was less inflamed than that of normal mice. The researchers then went on to discover that by transferring immune cells lacking T-bet to young, lean mice they were able to improve insulin sensitivity. “It appears that T-bet expression in the adaptive immune system is able to influence metabolic physiology,” adds Professor Graham Lord.
Although human obesity is often associated with insulin resistance and diabetes, this is not always the case.
“Our data suggests that obesity can be uncoupled from insulin resistance, through the absence of T-bet,” says Howard. Several of the main drugs currently used to treat type 2 diabetes work by improving insulin sensitivity.
Further studies are needed to identify other molecules in the pathway of action of T-bet which could pave the way for future drug development in the treatment of type 2 diabetes. The administration of specific immune cells as immunotherapy to improve insulin resistance may also one day become a therapeutic possibility.
“This is just the start,” says Howard. “The idea that the immune system can impact on metabolism is very exciting, but more research needs to be done before we can bring this work from the bench to the bedside for the benefit of patients.”
The UK Medical Research Council funded the study.
Source: King’s College London