New discoveries about “brown fat” could lead to treatments for obesity and related diseases such as diabetes, British researchers say.
A team at the University of East Anglia and the University of Cambridge, with colleagues, have revealed for the first time the molecular structure uncoupling protein 1 (UCP1).
This protein allows brown fat tissue to burn off calories as heat, in contrast to conventional white fat that stores calories.
Writing in Science Advances, the team, which also included collaborators from the University of Pennsylvania, USA, and the Free University of Brussels, Belgium, say their findings provide crucial molecular details that will help in the development of therapeutics that activate UCP1 artificially to burn off excess calories from fat and sugar.
Dr Paul Crichton, from UEA’s Norwich Medical School, said: “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.”
Using the Krios G3i, a cryogenic electron microscope at the Penn Singh Center for Nanotechnology, the team viewed UCP1 in atomic detail.
Lead researcher Prof Edmund Kunji from the University of Cambridge said they found 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,” he said. “This is a significant breakthrough in this field.”
Jones SA, Gogoi P, Ruprecht JJ et al. Structural basis of purine nucleotide inhibition of human uncoupling protein 1. Science Advances. May 2023; doi: 10.1126/sciadv.adh4251
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