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Un ciclo de sustrato impulsado por la creatina mejora el gasto energético y la termogénesis en la grasa beige
Lawrence Kazak1, Edward T Chouchani1, Mark P Jedrychowski2
1Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard University Medical School, Boston, MA 02115, USA.
Cell
|October 27, 2015
Resumen
Este estudio revela el metabolismo de la creatina
Área de la Ciencia:
- Biología del tejido adiposo
- La función mitocondrial
- Regulación del metabolismo
Sus antecedentes:
- Los tejidos adiposos termogénicos marrones y beige disipan energía en forma de calor, crucial para combatir la obesidad y la diabetes.
- Comprender las adaptaciones inducidas por el frío en estos tejidos es clave para la investigación metabólica.
Objetivo del estudio:
- Investigar las adaptaciones funcionales en los tejidos adiposos marrones y beige durante la exposición al frío utilizando proteómica cuantitativa.
- Identificar nuevas vías metabólicas implicadas en la termogénesis y el gasto energético.
Principales métodos:
- Proteómica mitocondrial cuantitativa para analizar la expresión de proteínas en los tejidos adiposos.
- Ensayos para medir la respiración mitocondrial y la actividad enzimática.
- Manipulaciones genéticas y farmacológicas para evaluar el papel del metabolismo de la creatina.
Principales resultados:
- El metabolismo arginina/creatina identificado como una firma distinta en el tejido adiposo beige.
- La creatina mejora la respiración en las mitocondrias de grasa beige, especialmente cuando la ADP está limitada.
- La exposición al frío regula los genes mitocondriales de la creatina quinasa y el metabolismo de la creatina en la grasa beige murina.
- Los niveles reducidos de creatina disminuyen el gasto energético y la tasa metabólica del tejido adiposo.
- Los genes del metabolismo de la creatina se inducen cuando la termogénesis dependiente de la UCP1 está alterada, y la reducción de la creatina reduce la temperatura corporal en ratones con deficiencia de Ucp1.
Conclusiones:
- Un ciclo inútil de metabolismo de la creatina está relacionado con el gasto energético del tejido adiposo.
- El metabolismo de la creatina juega un papel importante en la homeostasis térmica y la termogénesis adaptativa.
- Dirigirse al metabolismo de la creatina podría ofrecer estrategias terapéuticas para los trastornos metabólicos.
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