Lifespan of glucose-controlling molecule could be extended, helping protect against obesity, research suggests

While it would still need to be demonstrated in humans, it is hoped that the findings from the Nottingham Trent University-led study could be significant, by identifying a new therapeutic target for obesity and metabolic diseases such as type 2 diabetes.

Carnosine occurs naturally in the body in blood and tissues and it is thought it could play a role in protecting against obesity by regulating blood sugar, or glucose, within the body.

But the compound is broken down  quickly by damaging ‘carnosinase’ enzymes, which trigger chemical reactions in the body.

As part of the study, however, the researchers discovered that by giving mice a molecule almost identical to carnosine – and which was resistant to breakdown – the enzymes would bind to this instead.

Not only did the approach increase the lifespan and effectiveness of carnosine, but the study also showed that mice fed a high-fat diet gained ten percent less weight than those on a high-fat diet without the molecule.

Computational analysis of more than 53,000 molecules had helped the team to identify those most carnosine-like, in terms of size and shape, and resistant to carnosinase enzymes, before N-methyl-[6-(2-furyl)pyrid-3-yl]methylamine was selected as the most appropriate.

Between 1990 and 2017 the global deaths attributed to high body mass index more than doubled from 2.2 million to 4.7 million people.

Obesity levels also track closely with type 2 diabetes, where the figure has been projected to rise from an estimated 451 million adults worldwide in 2017 to 693 million by 2045.

While more work needs to be undertaken to understand the exact mechanism behind this effect and to determine the potential benefit in humans, the researchers argue that carnosinase inhibition could also help mitigate the risk from a range of other associated diseases, including cardiovascular disease, kidney disease and cancer.

“Responding to the twin challenge of obesity and type 2 diabetes requires timely and effective intervention aimed at counteracting the disease burden generated by high BMI,” said senior author Dr Mark Turner, an Associate Professor in Nottingham Trent University’s School of Science and Technology.

He said: “Carnosine is naturally-occurring and has anti-inflammatory and anti-glycating properties, so can help to regulate blood sugar in the body. While it can help to protect us against obesity and type 2 diabetes, however, it turns over extremely quickly in the body.

“We have found that by inhibiting these damaging enzymes we can prevent the breakdown of carnosine, keep it in the body for longer and extend its protective effects.

“Through computational modelling we were able to identify a molecule almost identical to carnosine which these enzymes were able to fit and bind to almost like a key inside a lock.

“We hope that our approach can potentially provide new therapeutic options against obesity and related diseases.”

The next stage of the work will be to investigate the exact mechanisms through which this process occurs, with the aim being to generate even more effective potential new drug therapies.

The research, which also involved King’s College London and Manchester Metropolitan University, is published in the journal Life Sciences.