Soler Vázquez, M. CarmenRomero Romero, María del MarTodorčević, MarijanaDelgado, KatiaCalatayud Aristoy, CarlesBenítez Amaro, AleydaLa Chica Lhoëst, Maria TeresaMera Nanín, PaulaZagmutt Caroxa, SebastiánBastías-Pérez, MarianelaIbeas, KevinCasals, NúriaEscolà Gil, Joan CarlesLlorente Cortés, VicentaConsiglio, AntonellaSerra i Cucurull, DolorsHerrero Rodríguez, Laura2023-07-252023-07-252023-051096-717637088334https://hdl.handle.net/2445/201162Obesity and its associated metabolic comorbidities are a rising global health and social issue, with novel therapeutic approaches urgently needed. Adipose tissue plays a key role in the regulation of energy balance and adipose tissue-derived mesenchymal stem cells (AT-MSCs) have gained great interest in cell therapy. Carnitine palmitoyltransferase 1A (CPT1A) is the gatekeeper enzyme for mitochondrial fatty acid oxidation. Here, we aimed to generate adipocytes expressing a constitutively active CPT1A form (CPT1AM) that can improve the obese phenotype in mice after their implantation. AT-MSCs were differentiated into mature adipocytes, subjected to lentivirus-mediated expression of CPT1AM or the GFP control, and subcutaneously implanted into mice fed a high-fat diet (HFD). CPT1AM-implanted mice showed lower body weight, hepatic steatosis and serum insulin and cholesterol levels alongside improved glucose tolerance. HFD-induced increases in adipose tissue hypertrophy, fibrosis, inflammation, endoplasmic reticulum stress and apoptosis were reduced in CPT1AM-implanted mice. In addition, the expression of mitochondrial respiratory chain complexes was enhanced in the adipose tissue of CPT1AM-implanted mice. Our results demonstrate that implantation of CPT1AM-expressing AT-MSC-derived adipocytes into HFD-fed mice improves the obese metabolic phenotype, supporting the future clinical use of this ex vivo gene therapy approach.17 p.application/pdfengcc-by-nc-nd (c) Soler-Vázquez, M. Carmen et al., 2023https://creativecommons.org/licenses/by-nc-nd/4.0/https://creativecommons.org/licenses/by-nc-nd/4.0/ObesitatTeixit adipósInflamacióGlucosaRatolins (Animals de laboratori)ObesityAdipose tissuesInflammationGlucoseMice (Laboratory animals)info:eu-repo/semantics/article7334852023-07-25info:eu-repo/semantics/openAccess