A similar thing happened when they gave obese mice a lipid called alpha-galactosylceramide (aGC), which activates iNKT cells – they lost weight and got healthier, despite the high-fat fare.
“The mice that received only one dose of aGC to activate their iNKT cells continued to eat and were not sick, but lost weight and their diabetes was greatly improved,” says Lynch, who points out that the compound has been used in humans before, but not for this purpose.
The human data in the new study came from patients attending the weight management clinic in St Columcille’s Hospital in Loughlinstown.
“Over 1,000 patients have now given blood samples to help the research,” says Prof Donal O’Shea, a consultant endocrinologist at St Columcille’s and St Vincent’s University Hospital who runs a weight management service for adults.
“The idea for this work came from their generosity and is opening up a new field in the area of obesity and diabetes research. It wouldn’t have happened without them.”
O’Shea is a co-author on the new study and he believes it will change the perception of obesity by highlighting how the body’s innate immune system could be making it harder for people who are obese to lose excess weight, in part because they lack iNKT cells.
“Obesity affects the immune system – we knew that alright – but the immune system affecting weight and obesity wasn’t on the agenda,” he says of the results they saw in mice. “It very soon made sense though.
“Weight loss is a huge threat to any living cell – and this work shows that the immune system is there to maintain weight. I think the long-term impact of the recognition that your innate or primal immune system is involved in regulating weight will change how we perceive the fight against obesity – and it certainly should drive the imperative for prevention. If your primal immune response is involved in defending against weight loss – that becomes a very tough battle.”
Prof O’Shea notes that both obesity and the immune system are complex, and it will be a while before we understand the interplay there. “Lydia’s work and the other work in the area puts the immune system firmly on the pitch as a player in how our weight is controlled,” he says. “It will be some time before we have the mechanisms worked out – and new therapeutic strategies arising from it.”