Weight Loss Success Before and After

Desbloqueando los secretos de la “grasa buena”: el descubrimiento de proteínas avanza en los tratamientos potenciales para la obesidad y la diabetes

Los científicos han revelado la estructura atómica de UCP1, una proteína clave para quemar calorías en la grasa parda “buena”. Este descubrimiento, habilitado por un microscopio electrónico criogénico, ofrece información sobre posibles tratamientos para la pérdida de peso y métodos para regular la temperatura corporal a través de la termogénesis.

Los hallazgos representan los primeros detalles estructurales de la proteína de desacoplamiento 1 (UCP1), que permite que el tejido graso queme calorías en forma de calor.

Una nueva investigación ha revelado información sobre cómo el tejido “graso bueno” podría aprovecharse para combatir la obesidad y eliminar la glucosa de la sangre, lo que ayuda a controlar la diabetes. Publicado hoy en

Human bodies consist of two types of fat: brown and white. Brown fat breaks down blood sugar (glucose) and fat molecules, generating heat in response to cold temperatures helping to maintain normal body temperature. The majority of fat in humans is white fat, and building up too much white fat contributes to obesity and other health issues.

Using the Krios G3i, a cryogenic electron microscope at the Penn Singh Center for Nanotechnology researchers were able to view mitochondrial uncoupling protein 1 (UCP1)—a protein which allows fat tissue to burn off calories as heat—in atomic detail for the first time. This work uncovered new insights into how this protein’s activity in brown fat cells could potentially be harnessed for weight loss.

Human Uncoupling Protein in Brown Adipose Tissue

The human uncoupling protein in brown adipose tissue in its inactive form (left), inhibited by a nucleotide, and in its activated form (right), which short-circuits the mitochondrion to produce heat. Credit: Penn Medicine

“This is an exciting development that follows more than four decades of research into what UCP1 looks like and how it works,” said Vera Moiseenkova-Bell, PhD, a professor 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 collaboration between everyone involved.”

In mammals, UCP1 gives brown fat a specialized ability to burn calories as heat for maintaining a stable body temperature. When activated by fatty acids, UCP1 short-circuits the mitochondria—known as the powerhouse of the cell for its work releasing energy from food—by allowing protons to seep across mitochondrial inner membrane. The short-circuiting generates heat and allowing the body to regulate its temperature through a process called thermogenesis.

For more on this research, see 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 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 funded 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.

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