|
Title:
|
Liver CPT1A gene therapy reduces diet‐induced hepatic steatosis in mice and highlights potential lipid biomarkers for human NAFLD
|
|
Author:
|
Weber, Minéia; Mera, Paula; Casas, Josefina; Salvador, Javier; Rodríguez, Amaia; Alonso, Sergio; Sebastián, David; Soler-Vázquez, M. Carmen; Montironi, Carla; Recalde, Sandra; Fucho, Raquel; Calderón-Domínguez, María; Mir, Joan Francesc; Bartrons, Ramon; Escola-Gil, Joan Carles; Sánchez-Infantes, David; Zorzano, Antonio; Llorente-Cortes, Vicenta; Casals i Farré, Núria; Valentí, Víctor; Frühbeck, Gema; Herrero Rodríguez, Laura; Serra, Dolors
|
|
Notes:
|
The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased drastically due to the global obesity pandemic but at present there are no approved therapies. Here, we aimed to revert high‐fat diet (HFD)‐induced obesity and NAFLD in mice by enhancing liver fatty acid oxidation (FAO). Moreover, we searched for potential new lipid biomarkers for monitoring liver steatosis in humans. We used adeno‐associated virus (AAV) to deliver a permanently active mutant form of human carnitine palmitoyltransferase 1A (hCPT1AM), the key enzyme in FAO, in the liver of a mouse model of HFD‐induced obesity and NAFLD. Expression of hCPT1AM enhanced hepatic FAO and autophagy, reduced liver steatosis, and improved glucose homeostasis. Lipidomic analysis in mice and humans before and after therapeutic interventions, such as hepatic AAV9‐hCPT1AM administration and RYGB surgery, respectively, led to the identification of specific triacylglyceride (TAG) specie (C50:1) as a potential biomarker to monitor NAFFLD disease. To sum up, here we show for the first time that liver hCPT1AM gene therapy in a mouse model of established obesity, diabetes, and NAFLD can reduce HFD‐induced derangements. Moreover, our study highlights TAG (C50:1) as a potential noninvasive biomarker that might be useful to monitor NAFLD in mice and humans. |
|
Subject(s):
|
-Oxidació
-Àcids grassos
-Teràpia genètica
-Esteatosi hepàtica
-Marcadors bioquímics
-Obesitat
-Fetge
-Oxidación
-Ácidos grasos
-Terapia genética
-Esteatosis hepática
-Marcadores bioquímicos
-Obesidad
-Hígado
-Oxidation
-Fatty acids
-Genetic therapy
-Hepatic steatosis
-Biochemical markers
-Obesity
-Liver
-61
-616.4 |
|
Rights:
|
© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
https://creativecommons.org/licenses/by-nc/4.0/
|
|
Document type:
|
Article
Article - Published version |
|
Published by:
|
John Wiley & Sons, Inc.
|
|
Share:
|
|
