A protein to demystify the molecular basis of obesity has been uncovered by an international collaboration of a team of researchers from University of East Anglia, University of Cambridge, University of Pennsylvania, and Free University of Brussels.
The study unfolded molecular structure of the protein UCP1 (Uncoupling Protein 1), a 33 kDa mitochondrial carrier protein, which plays a pivotal role in assisting brown fat tissue to utilize calories as heat, rather than storing calories as in white fat. This realization could offer advancement of therapies that artificially stimulate UCP1, enabling the burning of surplus fat and sugar-derived calories. A breakthrough in overcoming obesity and diabetes to a larger margin of population.Â
The focus of the first author of the study, Scott Jones, has since start been to puzzle out the structure of UCP1. Now the structure has been published, his main focus is to analyze its working and regulation in the body. The co-author Dr. Martin King elaborated how prosperous research collaborations could be. It was a project spanning a lot more than 10 years, but through prolific minds working on their own skillfulness, the project was able to draw a meaningful conclusion.
The Good Fat or the Bad Fat?
Brown fat is also considered to be ‘good fat’ because it helps the body to regulate temperature by catabolizing blood sugar and fat molecules to generate heat. The problem is, our bodies contain maximum fat as white fat which is the source of obesity. The white fat persistently stores fat, and excess of stored fat leads to obesity.
Considerable efforts have been made to discover strategies that might promote the development of brown fat and also to catalyze the conversion of brown fat from white fat. This would suggest a significant increase in fat metabolism and also combat related disorders. However, even if the presence of brown fat is multiplied, the activation of UCP1 remains essential to fully harness its advantages.
The Atomic Study
By employing the Krios G3i cryogenic electron microscope located at Penn Singh Center for Nanotechnology, the researchers observed protein at its atomic level. Through this, an interesting development came into view.
The scientists visualized the existence of protein UCP1 in brown fat cells. How a regulator molecule binds with the protein to hinder its activity and on the other hand, how activating molecules bind with the protein UCP1 to switch it on and initiate fat catabolism. Upon activation, the UCP1 initiates the release of protons through the inner mitochondrial membrane, propelling mitochondria to generate heat. On the contrary, purine nucleotides have been identified to prevent the release of protons by sewing itself to the mitochondrial UCP1.
The researchers name it a breakthrough discovery. The study of activated conformations of mitochondrial Uncoupling Protein 1 would also provide therapeutic relief to diabetic patients as the brown fat cells happen to eliminate blood glucose levels as well.
