Breakthrough in understanding of ‘good’ brown fat could open door to obesity and diabetes treatments

A “significant breakthrough” has been made in the search for treatments for obesity and related diseases such as diabetes.

An international study involving the University of Cambridge is the first to reveal the molecular structure of a protein called Uncoupling protein 1 (UCP1) which allows brown fat tissue – considered ‘good fat’ – to burn off calories as heat. By contrast, conventional white fat stores calories.

Lead researcher Professor Edmund Kunji, who leads a research group at the MRC Mitochondrial Biology Unit at Cambridge, said: “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.”

The team - also involving researchers from the University of East Anglia (UEA), the University of Pennsylvania and the Free University of Brussels - say the findings offer crucial details tol help in the development of treatments that activate UCP1 artificially, to burn off excess calories from fat and sugar.

This could eventually be used to combat obesity.

There has been four decades of research into the protein, but its molecular structure - key to understanding how it operates - has eluded scientists until now. They used the Krios G3i, a cryogenic electron microscope at the Penn Singh Center for Nanotechnology to view it in atomic detail for the first time.

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 newborns 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.”

The findings were published in the journal Science Advances.