Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/170660
Title: Liver CPT1A gene therapy reduces diet-induced hepatic steatosis in mice and highlights potential lipid biomarkers for human NAFLD
Author: Weber Blattes, Minéia
Mera Nanín, Paula
Casas Brugulat, Josefina
Salvador Bofill, Javier
Rodríguez, Amaia
Alonso Muñoz, Sergio
Sebastian, David
Soler-Vázquez, M Carmen
Montironi, Carla
Recalde, Sandra
Fucho Salvador, Raquel
Calderón Domínguez, María
Mir Bonnín, Joan Francesc
Bartrons Bach, Ramon
Escolà Gil, Joan Carles
Sánchez-Infantes, David
Zorzano Olarte, Antonio
Llorente Cortés, Vicenta
Casals, Núria
Valentí, Víctor
Frühbeck, Gema
Herrero Rodríguez, Laura
Serra i Cucurull, Dolors
Keywords: Obesitat
Àcids grassos
Malalties del fetge
Investigació farmacèutica
Obesity
Fatty acids
Liver diseases
Pharmaceutical research
Issue Date: 15-Jul-2020
Publisher: The Federation of American Society of Experimental Biology
Abstract: 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.
Note: Versió preprint del document publicat a: https://doi.org/10.1096/fj.202000678R
It is part of: The FASEB Journal , 2020
URI: http://hdl.handle.net/2445/170660
Related resource: https://doi.org/10.1096/fj.202000678R
ISSN: 0892-6638
Appears in Collections:Articles publicats en revistes (Bioquímica i Fisiologia)

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