UEA researchers make breakthrough in race to find treatments for obesity and diabetes

The study is the first to reveal the molecular structure of a protein which allows 'good fats' to burn off calories as heat

Author: Tom ClabonPublished 1st Jun 2023

Researchers at the University of East Anglia have made an important breakthrough in the race to find treatments for obesity and diabetes.

The study is the first to reveal the molecular structure of a protein- called ‘Uncoupling protein 1’ (UCP1)- which allows 'good fats' to burn off calories as heat.

It's in contrast to conventional 'white fat' or 'bad fats' that stores calories.

This work has been done via an international collaboration between UEA, the University of Cambridge, the University of Pennsylvania and the Free University of Brussels.

The team say that their findings provide crucial molecular details that will help develop therapeutic treatments that could one day combat obesity and related diseases, such as diabetes.

"Too much white fat leads to obesity"

Dr Paul Crichton, from UEA’s Norwich Medical School, said:

“As well as the conventional white fat that we are all familiar with, we can also develop brown fat.

“Brown fat is the good fat – it breaks down blood sugar and fat molecules to create heat and help maintain body temperature.

“Most of our fat, however, is white fat, which stores energy - and too much white fat leads to obesity.

“UCP1 is the key protein that allows the specialised brown fat to burn off calories as heat.

“We know that mammals switch on UCP1 activity in brown fat tissue to protect against the cold and to maintain body temperature - especially in new-borns, that cannot yet shiver to keep warm.

“Brown fat varies in humans, where it correlates with leanness in the population – and there has been a lot of interest in how to increase brown fat and activate UCP1 therapeutically, as a potential way to treat obesity.

“A lot of research has been focusing on finding ways to encourage brown fat and how to turn white fat into brown fat – in order to burn more calories and fight metabolic disease.

“But even with more brown fat – UCP1 must still be ‘switched on’ to gain full benefit. And research has been hampered by a lack of details on the molecular make up of UCP1.

"Despite more than 40 years of research, we did not know what UCP1 looks like to understand how it works – until now.”

"This is a significant breakthrough in this field"

Lead researcher Prof Edmund Kunji, from the University of Cambridge, said:

“Our paper reveals, for the first time, the structure of UCP1 in atomic detail, and how its activity in brown fat cells is inhibited by a key regulatory molecule.”

"Using the Krios G3i, a cryogenic electron microscope at the Penn Singh Center for Nanotechnology, the team were able to view UCP1 in atomic detail.

"Our work shows how a regulator binds to prevent UCP1 activity, but more importantly the structure will allow scientists to rationalise how activating molecules bind to switch the protein on, leading to the burning of fat.

“The activated tissue can also remove glucose from the blood, which can help control diabetes.

“This is a significant breakthrough in this field."

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