Newswise — Scientists at the University of East Anglia and the University of Cambridge have achieved a significant breakthrough in the pursuit of remedies for obesity and its associated ailments, including diabetes.
A recent publication presents the pioneering revelation of the molecular composition of 'Uncoupling protein 1' (UCP1), marking a significant milestone in scientific research.
This specific protein enables the thermogenic capacity of brown adipose tissue, commonly known as "good fat," to dissipate calories as heat, distinguishing it from conventional white fat, which primarily stores calories.
The groundbreaking achievement was accomplished through an international partnership involving 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 therapeutics that activate UCP1 artificially to burn off excess calories from fat and sugar.
And that this could one day combat obesity and related diseases, such as diabetes.
Dr. Paul Crichton, affiliated with UEA's Norwich Medical School, expressed, "In addition to the well-known white fat, we also have the ability to cultivate brown fat."
"Brown fat, often referred to as 'good fat,' plays a beneficial role in breaking down blood sugar and fat molecules, generating heat, and contributing to the regulation of 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.
"It is well-established that mammals activate UCP1 function in brown adipose tissue to defend against cold temperatures and regulate body temperature, particularly in newborns who lack the ability to shiver for warmth."
"Brown fat exhibits variations among humans and is associated with a leaner physique in the population. Consequently, there has been considerable interest in strategies to enhance brown fat and stimulate UCP1 as a potential therapeutic approach for addressing obesity."
"Extensive research efforts have been dedicated to discovering methods to promote the development of brown fat and convert white fat into brown fat. This pursuit aims to enhance calorie burning and combat metabolic disorders."
"However, even with an increased presence of brown fat, the full benefits can only be realized when UCP1 is activated. The research progress has been impeded by the absence of comprehensive information regarding the molecular structure of UCP1. Despite over four decades of investigation, the understanding of UCP1's functionality was limited due to the lack of knowledge regarding its visual representation. This knowledge gap has now been bridged."
Professor Edmund Kunji, the lead researcher from the University of Cambridge, commented, "Our publication presents the atomic-level structure of UCP1 for the first time, along with insights into how its function within brown fat cells is suppressed by a crucial regulatory molecule."
Utilizing the Krios G3i, a cryogenic electron microscope located at the Penn Singh Center for Nanotechnology, the research team successfully examined UCP1 with exceptional precision at the atomic level.
Vera Moiseenkova-Bell, an associate professor of Pharmacology and faculty director of the Beckman Center for Cryo-Electron Microscopy, expressed enthusiasm, stating, "This remarkable advancement comes after over forty years of research focused on unraveling the visual and functional aspects of UCP1."
Professor Kunji elaborated, stating, "Our study demonstrates the binding mechanism of a regulatory molecule that inhibits UCP1 activity. Furthermore, the structural insights obtained will enable scientists to better understand how activating molecules bind to UCP1, initiating its activation and promoting fat burning."
“The activated tissue can also remove glucose from the blood, which can help control diabetes.
“This is a significant breakthrough in this field,” he added.
This research received support from various funding sources, including the Medical Research Council, the Biological and Biotechnological Sciences Research Council, and the National Institutes of Health/National Institute of General Medical Sciences. The discovery of Nanobody was funded by the Instruct-ERIC, which is part of the European Strategy Forum on Research Infrastructures, as well as the Research Foundation - Flanders and the Strategic Research Program of the Vrije Universiteit Brussel.
‘Structural basis of purine nucleotide inhibition of human uncoupling protein 1’ is published in the journal Science Advances.
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