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| Home > Articles > Published articles > Liver CPT1A gene therapy reduces diet-induced hepatic steatosis in mice and highlights potential lipid biomarkers for human NAFLD |
(Instituto de Salud Carlos III) (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas) (Clínica Universidad de Navarra) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas) (Universitat de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Universitat de Barcelona) (Universitat de Barcelona) (Universitat de Barcelona) (Universitat de Barcelona) (Universitat de Barcelona) (Institut d'Investigació Biomèdica Sant Pau) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas) (Institut d'Investigació Biomèdica Sant Pau) (Universitat Internacional de Catalunya) (Clínica Universidad de Navarra) (Clínica Universidad de Navarra) (Instituto de Salud Carlos III) (Instituto de Salud Carlos III)| Date: | 2020 |
| 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. |
| Grants: | Ministerio de Economía y Competitividad SAF2014-52223-C2-1-R Agencia Estatal de Investigación SAF2017-83813-C3-1-R Instituto de Salud Carlos III PI18/01584 Instituto de Salud Carlos III PI17/00412 Instituto de Salud Carlos III PI18/01484 Instituto de Salud Carlos III PI17/01455 Ministerio de Economía y Competitividad CP15/00106 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | AAV ; CPT1A ; Fatty-acid oxidation ; Gene therapy ; Hepatic steatosis ; Lipid biomarker ; Obesity |
| Published in: | FASEB Journal, Vol. 34 Núm. 9 (january 2020) , p. 11816-11837, ISSN 1530-6860 |
