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2023-05

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cc-by-nc-nd (c) Soler-Vázquez, M. Carmen et al., 2023
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/201162

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

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https://doi.org/10.1016/j.ymben.2023.04.010

Abstract

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.

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Obesitat, Teixit adipós, Inflamació, Glucosa, Ratolins (Animals de laboratori)

Subject (English)

Obesity, Adipose tissues, Inflammation, Glucose, Mice (Laboratory animals)

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Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citation

SOLER VÁZQUEZ, M. Carmen, et al. Implantation of CPT1AM-expressing adipocytes reduces obesity and glucose intolerance in mice. Metabolic Engineering. 2023. Vol. 77, num. 256-272. ISSN 1096-7176. [consulted: 9 of August of 2026]. Available at: https://hdl.handle.net/2445/201162

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