An international team of scientists is one step closer to unlocking the molecular mechanisms at work in fat tissue, which could ultimately lead to treatments to effortlessly ‘switch on’ calorie burning.
For the first time, researchers at the University of East Anglia (UEA), the University of Cambridge, the University of Pennsylvania and the Free University of Brussels have viewed the molecular structure of mitochondrial uncoupling protein 1 (UCP1) in such detail that they have new insights into how it switches on to kickstart fat burning.
In brown fat (aka ‘good fat’) cells, UPC1 enables the tissue to burn calories as heat, which is vital in mammals for protection against the cold and to maintain body temperature. Brown fat is generally considered ‘good’, because of its key metabolic function, as opposed to white fat, which our bodies store calories in and is responsible for most negative health conditions linked to excess weight.
“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,” said Paul Crichton, from UEA’s Norwich Medical School. “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."
Indeed, cracking the code on how to turn white fat into brown fat has long been the center of many studies. This discovery, four decades in the making, unravels the mechanics involved in fat burning, which the scientists believe can guide future treatments.
“Even with more brown fat – UCP1 must still be ‘switched on’ to gain full benefit,” Crichton added. “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.”
With atomic imaging, the scientists were able to detail the protein’s molecular structure, identifying the ‘gates’ that act as switches to turn on or off calorie burning. With this, scientists believe there’s a pathway to developing treatments to activate UCP1 artificially, in order to burn excess calories from fat and sugar.
“Our work shows how a regulator binds to prevent UCP1 activity, but more importantly the structure will allow scientists to rationalize how activating molecules bind to switch the protein on, leading to the burning of fat,” said lead researcher Edmund Kunji, professor from the University of Cambridge.
“The activated tissue can also remove glucose from the blood, which can help control diabetes,” he added. “This is a significant breakthrough in this field."
The study was published in the journal Science Advances.
Source: University of East Anglia