Scientists have achieved a significant milestone by elucidating the atomic structure of UCP1, a pivotal protein responsible for calorie burning in beneficial brown fat. Leveraging the capabilities of a cryogenic electron microscope, this groundbreaking discovery offers profound insights into potential weight loss treatments and strategies for regulating body temperature through thermogenesis.
This groundbreaking research unravels the intricate structural details of uncoupling protein 1 (UCP1), which empowers adipose tissue to convert calories into heat.
In a collaborative effort between the Perelman School of Medicine at the University of Pennsylvania, University of Cambridge, Free University of Brussels, and University of East Anglia, new findings have shed light on how harnessing the potential of “good fat” tissue could combat obesity and aid in glucose removal from the bloodstream, thereby contributing to the management of diabetes. The remarkable study has been published in Science Advances.
The human body comprises two types of fat: brown and white. While brown fat efficiently breaks down glucose and fat molecules to generate heat when exposed to cold temperatures, thereby maintaining optimal body temperature, the abundance of white fat, which constitutes the majority, leads to obesity and various health complications.
Employing the Krios G3i, a cryogenic electron microscope situated at the Penn Singh Center for Nanotechnology, researchers have accomplished the first-ever atomic-level visualization of mitochondrial uncoupling protein 1 (UCP1). This breakthrough has unveiled novel insights into the mechanisms by which this protein operates within brown fat cells, offering potential avenues for weight loss interventions.
The study captures the inactive form of the human uncoupling protein found in brown adipose tissue, inhibited by a nucleotide (left), and its activated form (right), which triggers heat production by bypassing the mitochondrion. Credit: Penn Medicine
Vera Moiseenkova-Bell, PhD, a professor of Systems Pharmacology and Translational Therapeutics and faculty director of the Beckman Center for Cryo-Electron Microscopy, expressed her enthusiasm, stating, “This development is truly exciting, building upon more than four decades of research focused on understanding the structure and functionality of UCP1. Such breakthroughs would not have been possible without the exceptional collaboration among all the involved parties.”
UCP1 furnishes brown fat in mammals with a unique capacity to convert calories into heat, thereby enabling the maintenance of a stable body temperature. Upon activation by fatty acids, UCP1 facilitates a short-circuiting of the mitochondria—recognized as the cell’s powerhouses responsible for extracting energy from food—by allowing protons to permeate across the mitochondrial inner membrane. This process generates heat, thereby enabling the body to regulate its temperature through thermogenesis.
For further information on this research, please refer to “The Breakthrough That Could Lead to New Obesity Treatments.”
Reference: “Structural basis of purine nucleotide inhibition of human uncoupling protein 1” by Scott A. Jones, Prerana Gogoi, Jonathan J. Ruprecht, Martin S. King, Yang Lee, Thomas Zögg, Els Pardon, Deepak Chand, Stefan Steimle, Danielle M. Copeman, Camila A. Cotrim, Jan Steyaert, Paul G. Crichton, Vera Moiseenkova-Bell, Edmund R. S. Kunji, 31 May 2023, Science Advances.
DOI: 10.1126/sciadv.adh4251
This research was supported by the Medical Research Council (MC_UU_00028/2, MC_UU_00015/1), the U.K. Biological and Biotechnological Sciences Research Council (BB/S009
Table of Contents
Frequently Asked Questions (FAQs) about protein discovery
What is the significance of the protein discovery mentioned in the text?
The protein discovery pertains to UCP1, a protein found in “good” brown fat. Understanding its atomic structure provides insights into calorie burning, potential treatments for obesity and diabetes, and methods for regulating body temperature through thermogenesis.
What is UCP1 and how does it contribute to weight loss?
UCP1, also known as uncoupling protein 1, is a protein found in brown fat tissue. When activated by fatty acids, UCP1 short-circuits the mitochondria, generating heat and allowing the body to burn calories. This activation process contributes to weight loss by increasing calorie expenditure.
How does brown fat differ from white fat?
Brown fat and white fat are two types of adipose tissue in the human body. Brown fat is known as “good fat” because it breaks down glucose and fat molecules to produce heat, helping to maintain normal body temperature. In contrast, white fat is the predominant type and excessive accumulation can lead to obesity and associated health problems.
What technology was used to uncover the atomic structure of UCP1?
The researchers utilized a cryogenic electron microscope, specifically the Krios G3i, at the Penn Singh Center for Nanotechnology. This advanced imaging technology allowed them to visualize UCP1 in atomic detail, providing crucial insights into its structure and function.
How can harnessing the potential of brown fat tissue combat obesity and diabetes?
By understanding the mechanisms of UCP1 and brown fat tissue, researchers aim to develop treatments that activate and enhance the calorie-burning capabilities of brown fat. This could aid in weight loss efforts and help regulate glucose levels in the bloodstream, contributing to the management of obesity and diabetes.
What are the implications of this protein discovery for future research?
This protein discovery opens up new avenues for further research in the field of obesity, diabetes, and thermogenesis. Scientists can now explore strategies to harness the potential of UCP1 and brown fat tissue for developing innovative treatments and interventions to address these health conditions.
More about protein discovery
- Science Advances: Structural basis of purine nucleotide inhibition of human uncoupling protein 1
- Perelman School of Medicine at the University of Pennsylvania: Research Highlights
- University of Cambridge: News Article
- University of East Anglia: News Release
- Beckman Center for Cryo-Electron Microscopy: Faculty Directory
6 comments
This protein discovery is a game changer! Understanding UCP1’s structure gives us valuable insights into how we can tackle obesity and diabetes. Exciting times ahead!
Woah, UCP1 is a rockstar! Short-circuiting mitochondria and burning calories? That’s some next-level stuff. Can’t wait to dive deeper into the research and learn more.
omg dis is sooo cool! dey found da struc of da protein nd now dey can make treatmnts 4 obesity n diabtis!! luv how scienc is advansin!
Brown fat FTW! It’s awesome how UCP1 helps burn calories as heat. Maybe we can find ways to activate it naturally and say bye-bye to extra pounds. Fingers crossed!
Cryo-EM FTW! The Krios G3i microscope is a beast. It’s revealing atomic details we’ve been chasing for decades. Can’t wait to see what other mysteries it uncovers!
Brown fat vs. white fat – the battle continues! But this discovery brings hope. Maybe we can tap into the power of brown fat to fight obesity and keep our bodies in balance. Let’s keep exploring!