Miniatura

Fitxers

702850.pdf (1.59 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2020-07-15

Llicència de publicació

cc by-nc (c) Weber Blattes et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/170660

Liver CPT1A gene therapy reduces diet-induced hepatic steatosis in mice and highlights potential lipid biomarkers for human NAFLD

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1096/fj.202000678R

Resum

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.

Matèries

Obesitat, Àcids grassos, Malalties del fetge, Investigació farmacèutica

Matèries (anglès)

Obesity, Fatty acids, Liver diseases, Pharmaceutical research

Citació

Col·leccions

Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citació

WEBER BLATTES, Minéia, MERA NANÍN, Paula, CASAS BRUGULAT, Josefina, SALVADOR BOFILL, Javier, RODRÍGUEZ, Amaia, ALONSO MUÑOZ, Sergio, SEBASTIÁN MUÑOZ, 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. Liver CPT1A gene therapy reduces diet-induced hepatic steatosis in mice and highlights potential lipid biomarkers for human NAFLD. _The FASEB Journal_. 2020. Vol. 34, núm. 9, pàgs. 11816-11837. [consulta: 27 de febrer de 2026]. ISSN: 0892-6638. [Disponible a: https://hdl.handle.net/2445/170660]

Exportar metadades

JSON - METS

Compartir registre