Details

Autor(en) / Beteiligte

• Soler-Vázquez, M Carmen
• Romero, María del Mar
• Todorcevic, Marijana
• Delgado, Katia
• Calatayud, Carles
• Benitez -Amaro, Aleyda
• La Chica Lhoëst, Maria Teresa
• Mera, Paula
• Zagmutt, Sebastián
• Bastías-Pérez, Marianela
• Ibeas, Kevin
• Casals, Núria
• Escolà-Gil, Joan Carles
• Llorente-Cortés, Vicenta
• Consiglio, Antonella
• Serra, Dolors
• Herrero, Laura

Titel

Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice

Ist Teil von

• Metabolic engineering, 2023-05, Vol.77, p.256-272

Ort / Verlag

Belgium: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Obesity 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. [Display omitted] •AT-MSCs could be isolated from different fat depots of lean and obese mice.•Implantation of CPT1AM-expressing AT-MSC-derived adipocytes improves obesity.•Implantation of CPT1AM-expressing AT-MSC-derived adipocytes reduces hyperglycemia.•CPT1AM-implanted mice showed improved HFD-induced adipose tissue derangements.•Novel pre-clinical cell-based gene therapy for obesity and associated diseases.