Researchers have revealed the atomic structure of UCP1, a protein secret to calorie burning in good brown fat. This discovery, enabled by a cryogenic electron microscope, uses insights into possible weight reduction treatments and methods for regulating body temperature by means of thermogenesis.
Findings represent the first structural details of uncoupling protein 1 (UCP1), which allows fat tissue to burn off calories as heat.
New research has unlocked insights into how “great fat” tissue could possibly be harnessed to combat weight problems and remove glucose from the blood, assisting to control diabetes. Released today in Science Advances, the work is a collaboration in between scientists with the Perelman School of Medicine at the University of Pennsylvania and University of Cambridge, Free University of Brussels, and University of East Anglia.
Human bodies include 2 types of fat: brown and white. Brown fat breaks down blood glucose (glucose) and fat particles, creating heat in reaction to cold temperature levels helping to keep normal body temperature. The bulk of fat in humans is white fat, and constructing up excessive white fat contributes to obesity and other health issues.
Human bodies consist of 2 types of fat: white and brown. Brown fat breaks down blood sugar (glucose) and fat molecules, creating heat in response to cold temperature levels helping to preserve regular body temperature level. The bulk of fat in people is white fat, and developing up too much white fat contributes to obesity and other health concerns.
In mammals, UCP1 offers brown fat a specialized capability to burn calories as heat for preserving a steady body temperature level.
Using the Krios G3i, a cryogenic electron microscope at the Penn Singh Center for Nanotechnology scientists were able to view mitochondrial uncoupling protein 1 (UCP1)– a protein which enables fat tissue to burn calories as heat– in atomic detail for the very first time. This work uncovered brand-new insights into how this proteins activity in brown fat cells could potentially be harnessed for weight-loss.
The human uncoupling protein in brown fat in its non-active type (left), inhibited by a nucleotide, and in its activated type (right), which short-circuits the mitochondrion to produce heat. Credit: Penn Medicine
” This is an amazing advancement that follows more than four decades of research into what UCP1 appears like and how it works,” stated Vera Moiseenkova-Bell, PhD, a teacher of Systems Pharmacology and Translational Therapeutics and faculty director of the Beckman Center for Cryo-Electron Microscopy. “These new indings would not have been possible without the partnership in between everybody included.”
In mammals, UCP1 gives brown fat a specialized ability to burn calories as heat for keeping a stable body temperature level. When activated by fats, UCP1 short-circuits the mitochondria– called the powerhouse of the cell for its work launching energy from food– by allowing protons to seep throughout mitochondrial inner membrane. The short-circuiting generates heat and allowing the body to manage its temperature through a process called thermogenesis.
For more on this research, see The Breakthrough That Could Lead to New Obesity Treatments.
Referral: “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 work was supported by the Medical Research Council (MC_UU_00028/ 2, MC_UU_00015/ 1), by the U.K. Biological and Biotechnological Sciences Research Council (BB/S00940X/1) and by National Institutes of Health/National Institute of General Medical Sciences (R01 GM073791, F31 HL156431). Nanobody discovery was moneyed by the Instruct-ERIC part of the European Strategy Forum on Research infrastructures, and the Research Foundation– Flanders, and the Strategic Research Program of the Vrije Universiteit Brussel.
